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WARNING: SUICIDAL THOUGHTS AND BEHAVIORS Selective serotonin reuptake inhibitors (SSRIs) increased the risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term trials for the treatment of major depressive disorder and other psychiatric disorders. Because paroxetine is an SSRI, closely monitor paroxetine-treated patients closely for emergence of suicidal thoughts and behaviors [see Warnings and Precautions ( 5.1 )] . Paroxetine is not approved for use in any psychiatric condition or in pediatric and young adult patients [see Indications and Usage ( 1 ) and Use in Specific Populations ( 8.4 )] . WARNING: SUICIDAL THOUGHTS AND BEHAVIORS See full prescribing information for complete boxed warning. Antidepressants, including selective serotonin reuptake inhibitors (SSRIs), increased the risk of suicidal thoughts and behavior in pediatric and young adult patients with major depressive disorder and other psychiatric disorder. Because paroxetine is an SSRI, closely monitor patients for clinical worsening and for emergence of suicidal thoughts and behaviors. Paroxetine is not approved for use in pediatric and young adult patients ( 5.1 ).

1 INDICATIONS AND USAGE Paroxetine capsules are indicated for the treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause. Limitations of Use : Paroxetine capsules are not indicated for the treatment of any psychiatric condition. Paroxetine capsules have a lower recommended paroxetine dosage than that used to treat major depressive disorder, obsessive compulsive disorder, panic disorder, generalized anxiety disorder, social anxiety disorder, and post-traumatic stress disorder. The safety and effectiveness of the lower paroxetine capsules dosage have not been established for any psychiatric condition. Patients who require paroxetine for treatment of a psychiatric condition should discontinue paroxetine capsules and initiate a paroxetine-containing product that is indicated for such use. Paroxetine is a selective serotonin reuptake inhibitor (SSRI) indicated for the treatment of moderate to severe vasomotor symptoms associated with menopause (VMS) ( 1 ) Limitations of Use : Paroxetine capsules are not indicated for the treatment of any psychiatric condition ( 1 )

2 DOSAGE AND ADMINISTRATION • The recommended dosage of paroxetine capsules is 7.5 mg once daily, at bedtime ( 2.1 ) 2.1 Recommended Dosage The recommended oral dosage of paroxetine capsules for the treatment of moderate to severe VMS associated with menopause is 7.5 mg once daily, at bedtime, with or without food [see Clinical Pharmacology ( 12.3 )] . 2.2 Use of Paroxetine Capsules Before or After a Monoamine Oxidase Inhibitor Wait at least 14 days after discontinuation of a monoamine oxidase inhibitor (MAOI) before initiating therapy with paroxetine capsules. Conversely, allow at least 14 days after stopping paroxetine capsules before starting an MAOI [see Contraindications ( 4.1 ), Warnings and Precautions ( 5.2 ) and Drug Interactions ( 7.3 )] .

3 DOSAGE FORMS AND STRENGTHS Paroxetine capsules are available as 7.5 mg white opaque capsules printed with “544” in black ink on the cap and “7.5 mg” in black ink on the body. Each capsule contains 9.69 mg of paroxetine mesylate equivalent to 7.5 mg paroxetine base. Capsules: 7.5 mg ( 3 )

4 CONTRAINDICATIONS Paroxetine capsules are contraindicated in patients: • Taking, or within 14 days of stopping, MAOIs (including the MAOIs linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [see Warnings and Precautions ( 5.2 ), Drug Interaction ( 7 )] . • Taking thioridazine because of risk of QT prolongation [see Warnings and Precautions ( 5.3 ), Drug Interaction ( 7 )] . • Taking pimozide because of risk of QT prolongation [see Warnings and Precautions ( 5.3 ), Drug Interaction ( 7 )] . • With known hypersensitivity (e.g., anaphylaxis, angioedema, Stevens-Johnson syndrome) to paroxetine or to any of the inactive ingredients in paroxetine capsules [see Adverse Reactions ( 6.2 )] . Who are or become pregnant because menopausal VMS does not occur during pregnancy and paroxetine capsules may cause fetal harm [see Use in Specific Populations ( 8.1 )] . • Concurrent use with monoamine oxidase inhibitors (MAOI) or use within 14 days of MAOI use ( 2.2 , 4.1 , 5.2 , 7.3 ) • Use with thioridazine ( 4.2 , 7.1 ) • Use with pimozide ( 4.3 , 7.1 ) • Hypersensitivity to any ingredient in paroxetine capsules ( 4.4 ) • Pregnancy ( 4.5 , 8.1 )

5 WARNINGS AND PRECAUTIONS • Suicidality: Monitor for suicidality or unusual changes in behavior ( 5.1 ) • Serotonin Syndrome: Paroxetine capsules can cause serotonin syndrome with increased risk when co-administered with other serotonergic agents, but also when taken alone. If it occurs, discontinue paroxetine capsules and serotonergic agents and initiate supportive measures ( 5.2 , 7.3 ) • Tamoxifen: Efficacy of tamoxifen may be reduced when administered concomitantly with paroxetine capsules ( 5.3 , 7.1 ) • Abnormal Bleeding: Caution patients about the risk of bleeding associated with the concomitant use of paroxetine capsules and non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, or other drugs that affect coagulation ( 5.4 , 7.1 ) • Angle-Closure Glaucoma: Angle closure glaucoma has occurred in patients who have untreated anatomically narrow angles and who are treated with antidepressants. ( 5.5 ) • Hyponatremia: Can occur in association with syndrome of inappropriate antidiuretic hormone secretion (SIADH) (5.6) • Bone Fracture: Epidemiological studies have reported an association between SSRI treatment and fractures (5.7) • Activation of Mania/Hypomania: Screen for bipolar disorder and monitor for mania/ hypomania (5.8) • Seizures: Use cautiously in patients with a history of seizures or with conditions that potentially lower the seizure threshold (5.9) • Sexual Dysfunction: Paroxetine use may cause symptoms of sexual dysfunction. ( 5.10 ) 5.1 Suicidal Thoughts and Behaviors in Adolescents and Young Adults SSRIs increased the risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term trials for the treatment of major depressive disorder (MDD) and other psychiatric disorders - paroxetine capsules are not approved for use in any psychiatric condition or in pediatric and young adult patients [see Indications and Usage ( 1 ) and Use in Specific Populations ( 8.4 )] . There is limited information regarding suicidal thoughts and behaviors in females who use paroxetine capsules for treatment of moderate to severe VMS associated with menopause. The paroxetine capsules trials excluded females with a presence or history of previous psychiatric disorders. Monitor all paroxetine capsules-treated patients for any emergence of suicidal thoughts and behaviors, especially during the initial few months of paroxetine capsules therapy. Counsel family members to monitor for changes in behavior and to alert the health care provider if such changes occur. Consider discontinuing paroxetine capsules in patients who experience emergent suicidal thoughts or behaviors or symptoms that might be precursors to suicidal thoughts or behaviors, especially if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. 5.2 Serotonin Syndrome Paroxetine capsules can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, tramadol, meperidine, methadone, lithium, tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., monoamine oxidase inhibitors (MAOIs) [see Contraindications ( 4 ), Drug Interactions ( 7.3 )] . Serotonin syndrome can also occur when paroxetine capsules are used alone.

, meperidine, methadone, lithium, tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., monoamine oxidase inhibitors (MAOIs) [see Contraindications ( 4 ), Drug Interactions ( 7.3 )] . Serotonin syndrome can also occur when paroxetine capsules are used alone. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The concomitant use of paroxetine capsules with MAOIs is contraindicated. Do not start paroxetine capsules in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue. All reports with methylene blue that provided information on the route of administration involved intravenous administration in the dosage range of 1 mg/kg to 8 mg/kg. No reports involved the administration of methylene blue by other routes (such as oral or local tissue injection) or at lower dosages. If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking paroxetine capsules. The patient should be taken off paroxetine capsules before initiating treatment with the MAOI [see Contraindications (4.1)] . If concomitant use of paroxetine capsules with other serotonergic drugs (besides MAOIs) is clinically warranted, consider the increased risk of serotonin syndrome and carefully observe the patient, particularly during paroxetine capsules initiation [see Contraindications (4.1) Drug Interactions ( 7.3 )] . Monitor all patients taking paroxetine capsules for the emergence of serotonin syndrome. Discontinue paroxetine capsules and any concomitant serotonergic agents immediately if the above events occur and initiate supportive symptomatic treatment. 5.3 Potential Impact on Tamoxifen Efficacy Some studies have shown that the efficacy of tamoxifen, as measured by the risk of breast cancer relapse/mortality, may be reduced when concomitantly administered with paroxetine as a result of paroxetine’s irreversible inhibition of CYP2D6 and lower tamoxifen blood levels [see Drug Interactions ( 7.1 )] . However, other studies have failed to demonstrate such a risk. When tamoxifen is used for the treatment or prevention of breast cancer, weigh the likely benefit of paroxetine capsules for treating moderate to severe VMS associated with menopause vs. the risk of possible decreased tamoxifen effectiveness, and consider avoiding the concomitant use of paroxetine capsules. 5.4 Increased Risk of Bleeding SSRIs, including paroxetine capsules, increased the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), other antiplatelet drugs, warfarin, and other anticoagulants may add to this risk [see Drug Interactions ( 7.3 )] . Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Bleeding events related to SSRIs have ranged from ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages. Inform patients about the risk of bleeding associated with the concomitant use of paroxetine capsules and antiplatelet agents or anticoagulants [see Drug Interactions (7.1)] . For patients taking warfarin, carefully monitor the international normalized ratio.

a, epistaxis, and petechiae to life-threatening hemorrhages. Inform patients about the risk of bleeding associated with the concomitant use of paroxetine capsules and antiplatelet agents or anticoagulants [see Drug Interactions (7.1)] . For patients taking warfarin, carefully monitor the international normalized ratio. 5.5 Angle-Closure Glaucoma The pupillary dilation that occurs following use of SSRIs, including paroxetine capsules, may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy. Cases of angle-closure glaucoma associated with use of paroxetine have been reported. Avoid use of SSRIs, including paroxetine capsules, in patients with untreated anatomically narrow angles. 5.6 Hyponatremia Hyponatremia may occur as a result of treatment with SSRIs, including paroxetine capsules. Cases with serum sodium lower than 110 mmol/L have been reported in patients using SSRIs. Geriatric patients, patients taking diuretics, and those who are volume-depleted may be at greater risk of developing hyponatremia with SSRIs [see Use in Specific Populations ( 8.5 )] . Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which can lead to falls. Signs and symptoms associated with more severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death. In many cases, the hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). In patients with symptomatic hyponatremia, discontinue paroxetine capsules and institute appropriate medical intervention. 5.7 Bone Fracture Epidemiological studies on bone fracture risk following exposure to SSRIs have reported an association between SSRI treatment and fractures. It is unknown to what extent fracture risk is directly attributable to SSRI treatment. If a paroxetine capsules-treated patient presents with unexplained bone pain, point tenderness, swelling, or bruising, consider the possibility of a fragility fracture. 5.8 Screening Patients for Bipolar Disorder and Monitoring for Mania/Hypomania Paroxetine capsules are only indicated for the treatment of moderate to severe VMS and are not approved for use in treating either depression or bipolar depression. However, prior to initiating treatment with paroxetine capsules, all patients should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It is generally believed (though not established in controlled trials) that use of an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. 5.9 Seizures In clinical studies of another paroxetine product, seizures occurred in 0.1% of paroxetine-treated patients. Use paroxetine capsules cautiously in patients with a history of seizures or with conditions that potentially lower the seizure threshold. Discontinue paroxetine capsules in any patient who develops seizures. 5.10 Sexual Dysfunction Use of SSRIs, including paroxetine capsules, may cause symptoms of sexual dysfunction. In female patients, SSRI use may result in decreased libido and delayed or absent orgasm. It is important for prescribers to inquire about sexual function prior to initiation of paroxetine capsules and to inquire specifically about changes in sexual function during treatment because sexual function may not be spontaneously reported. When evaluating changes in sexual function, obtaining a detailed history (including timing of symptom onset) is important because sexual symptoms may have other causes.

etine capsules and to inquire specifically about changes in sexual function during treatment because sexual function may not be spontaneously reported. When evaluating changes in sexual function, obtaining a detailed history (including timing of symptom onset) is important because sexual symptoms may have other causes. Discuss potential management strategies to support patients in making informed decisions about treatment.

6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in labeling: • Suicidality [see Warnings and Precautions ( 5.1 )] • Serotonin syndrome [see Warnings and Precautions ( 5.2 )] • Abnormal bleeding [see Warnings and Precautions ( 5.4 )] • Angle-Closure Glaucoma [see Warnings and Precautions ( 5.5 )] • Hyponatremia [see Warnings and Precautions ( 5.6 )] • Bone Fracture [see Warnings and Precautions ( 5.7 )] • Mania/Hypomania [see Warnings and Precautions ( 5.8 )] • Seizure [see Warnings and Precautions ( 5.9 )] The most common adverse reactions (≥ 2%) reported in clinical trials were: headache, fatigue, and nausea/vomiting (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Solco Healthcare LLC at 1-866-257-2597 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot directly be compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to paroxetine in the following randomized, placebo-controlled trials for the treatment of moderate to severe VMS associated with menopause [see Clinical Studies ( 14 )]: (1) one 8-week Phase 2 trial, (2) one 12-week Phase 3 trial and (3) one 24-week Phase 3 trial. In these trials, a total of 635 postmenopausal females received paroxetine 7.5 mg administered orally once daily and 641 postmenopausal females received placebo. In these trials, 68% were White, 30% were Black or African American (30%), and 2% were other races, with a mean age of 55 years (range 40 to 73 years). Postmenopausal females with a history of suicidal ideation or suicidal behavior were excluded from these trials. Serious Adverse Reactions: In the pooled Phase 2 and Phase 3 trials, three paroxetine-treated patients reported a serious adverse reaction of suicidal ideation and one paroxetine-treated patient reported a serious adverse reaction of suicide attempt. There were no serious adverse reactions of suicidal ideation or suicide attempt reported among the placebo-treated patients. Adverse Reactions Leading to Study Discontinuation : A total of 4.7% of females taking paroxetine capsules discontinued from the clinical trials due to an adverse reaction, compared to 3.7% of females on placebo; the most frequent adverse reactions leading to discontinuation among paroxetine-treated females were: abdominal pain (0.3%), attention disturbances (0.3%), headache (0.3%), and suicidal ideation (0.3%). Common Adverse Reactions : Overall, based on investigators’ determinations about what events were likely to be drug-related, about 20% of postmenopausal females treated with paroxetine capsules reported at least 1 adverse reaction in the three controlled trials. The most common adverse reactions (≥ 2% and at a higher incidence in paroxetine capsules-treated females compared to placebo-treated females) reported in these trials were headache, fatigue/malaise/lethargy, and nausea/vomiting. Of these commonly reported adverse reactions, nausea occurred primarily within the first 4 weeks of paroxetine treatment and fatigue occurred primarily within the first week of paroxetine treatment, and decreased in frequency with continued therapy.

e trials were headache, fatigue/malaise/lethargy, and nausea/vomiting. Of these commonly reported adverse reactions, nausea occurred primarily within the first 4 weeks of paroxetine treatment and fatigue occurred primarily within the first week of paroxetine treatment, and decreased in frequency with continued therapy. The adverse reactions that occurred in ≥ 2% of paroxetine-treated patients and at a higher incidence in paroxetine-treated females compared to placebo-treated females are shown in Table 1 for the pooled Phase 2 and Phase 3 trials. Table 1: Incidence of Common Adverse Reactions in the Phase 2 and Phase 3 Trials of Postmenopausal Females with Moderate to Severe VMS 1 Incidence n (%) Paroxetine Capsules (n = 635) Placebo (n = 641) Headache 40 (6.3) 31 (4.8) Fatigue, malaise, lethargy 31 (4.9) 18 (2.8) Nausea, vomiting 27 (4.3) 15 (2.3) 1 ≥ 2% Paroxetine-treated patients and at a higher incidence in paroxetine-treated females compared to placebo-treated females. Adverse Reactions After Discontinuing Paroxetine Certain symptoms were seen more frequently in postmenopausal females at the time of discontinuation of paroxetine compared to discontinuation of placebo and have also been reported upon discontinuation of other paroxetine products, particularly after abrupt discontinuation. Adverse reactions reported after discontinuation of paroxetine included increased dreaming/nightmares, muscle cramps/spasms/twitching, headache, nervousness/anxiety, fatigue/tiredness, restless feeling in legs, and trouble sleeping/insomnia. While these adverse reactions were generally self-limiting, there have been reports of serious discontinuation symptoms with other paroxetine products. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of this and other paroxetine products. Because some of these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and Lymphatic System Disorders : Idiopathic thrombocytopenic purpura, Events related to impaired hematopoiesis (including aplastic anemia, pancytopenia, bone marrow aplasia, agranulocytosis). Cardiac Disorders : Atrial fibrillation, Pulmonary edema, Ventricular fibrillation, Ventricular tachycardia (including torsades de pointes). Gastrointestinal Disorders : Pancreatitis, Pancreatitis hemorrhagic, Vomiting. General Disorders and Administration Site Conditions : Death, Drug withdrawal syndrome, Malaise. Hepatobiliary Disorders : Drug-induced liver injury, Hepatic failure, Jaundice. Immune System Disorders : Anaphylaxis, Angioedema, Toxic epidermal necrolysis. Investigations : Elevated liver tests (the most severe cases were deaths due to liver necrosis, and grossly elevated transaminases associated with severe liver dysfunction). Metabolism and Nutrition Disorders : Diabetes mellitus inadequate control, Type 2 diabetes mellitus. Nervous System Disorders : Neuroleptic malignant syndrome, Paresthesia, Somnolence, Tremor, Anosmia, Hyposmia. Psychiatric Disorders : Aggression, Agitation, Anxiety, Confusional state, Depression, Disorientation, Homicidal ideation, Insomnia, Restlessness. Respiratory, Thoracic and Mediastinal Disorders : Pulmonary hypertension. Skin and Subcutaneous Tissue Disorders : Hyperhidrosis, Stevens-Johnson syndrome, Drug reaction with eosinophilia and systemic symptoms (DRESS).

<table width="100%"><col width="29%"/><col width="30%"/><col width="42%"/><tbody><tr><td rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"/><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Incidence n (%)</content></paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Paroxetine Capsules (n = 635)</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Placebo (n = 641)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Headache</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>40 (6.3)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>31 (4.8)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Fatigue, malaise, lethargy</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>31 (4.9)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>18 (2.8)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Nausea, vomiting</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>27 (4.3)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>15 (2.3)</paragraph></td></tr><tr><td colspan="3" valign="top"><paragraph>¹&#x2265; 2% Paroxetine-treated patients and at a higher incidence in paroxetine-treated females compared to placebo-treated females.</paragraph></td></tr></tbody></table>

7 DRUG INTERACTIONS Paroxetine is a strong CYP2D6 inhibitor. Co-administration of paroxetine capsules can alter concentrations of other drugs that are metabolized by CYP2D6. Consider potential drug interactions prior to and during therapy ( 5.3 , 7.1 , 7.3 ). See Full Prescribing Information for a list of clinically significant drug interactions ( 7.1 , 7.2 , 7.3 ) 7.1 Potential for Paroxetine Capsules to Affect Other Drugs Paroxetine is a strong CYP2D6 inhibitor. Clinical drug interaction studies have been performed with substrates of CYP2D6 and show that paroxetine can inhibit the metabolism of drugs metabolized by CYP2D6 [see Clinical Pharmacology ( 12.3 )] . Table 2 contains examples of drugs with a metabolism that may be affected by concomitant use with paroxetine capsules. Table 2 Effects of Paroxetine on Other Drugs Concomitant Drug Name Effect of Paroxetine on Other Drugs Clinical Recommendations Thioridazine Increased plasma concentrations of thioridazine Potential QTc prolongation Concomitant use of thioridazine and paroxetine capsules is contraindicated. Pimozide Increased plasma concentrations of pimozide. Potential QTc prolongation Concomitant use of pimozide and paroxetine capsules is contraindicated. Tamoxifen Reduced plasma concentrations of active tamoxifen metabolite Consider avoiding concomitant use of tamoxifen and paroxetine capsules. Tricyclic Antidepressants (TCA) (e.g., Desipramine) Increased plasma concentrations and elimination half-life Plasma TCA concentrations may need to be monitored and the TCA dosage may need to be reduced if a TCA is used concomitantly with paroxetine capsules. Monitor tolerability. Risperidone Increased plasma concentrations of risperidone A lower risperidone dosage may be necessary (see the risperidone Prescribing Information for). Monitor tolerability. Atomoxetine Increased exposure of atomoxetine A lower atomoxetine dosage of may be necessary (see atomoxetine Prescribing Information for). Monitor tolerability. Drugs Highly Bound to Plasma Protein (e.g., Warfarin) Increased free plasma concentrations The warfarin dosage may need to be reduced. Monitor tolerability and the International Normalized Ratio. Digoxin Decreased plasma concentrations of digoxin The digoxin dosage of may need to be increased. Monitor digoxin concentrations and clinical effect. Theophylline Increased plasma concentrations of theophylline The theophylline dosage of may need to be decreased. Monitor theophylline concentrations and tolerability. Use caution with concomitant use of paroxetine capsules with other drugs that are metabolized by CYP2D6, including nortriptyline, amitriptyline, imipramine, desipramine, fluoxetine, phenothiazines, risperidone, and Type 1C antiarrhythmics (e.g., propafenone, flecainide, and encainide). 7.2 Potential for Other Drugs to Affect Paroxetine Capsules The metabolism and pharmacokinetics of paroxetine may be affected by the induction and inhibition of drug metabolizing enzymes such as CYP2D6. Table 3 contains a list of drugs that may affect the pharmacokinetics of paroxetine capsules when administered concomitantly [see Clinical Pharmacology ( 12.3 )] . Table 3 Effects of Other Drugs on Paroxetine Concomitant Drug Name Effect of Concomitant Drug on Paroxetine Clinical Recommendations Phenobarbital Decreased paroxetine exposure Monitor clinical effect of paroxetine capsules. No paroxetine capsules dosage adjustment is needed.

ntly [see Clinical Pharmacology ( 12.3 )] . Table 3 Effects of Other Drugs on Paroxetine Concomitant Drug Name Effect of Concomitant Drug on Paroxetine Clinical Recommendations Phenobarbital Decreased paroxetine exposure Monitor clinical effect of paroxetine capsules. No paroxetine capsules dosage adjustment is needed. Phenytoin Decreased paroxetine exposure Fosamprenavir/ Ritonavir Decreased plasma concentration of paroxetine Cimetidine Increased plasma concentration of paroxetine Use caution if paroxetine capsules are used concomitantly with other drugs that inhibit CYP2D6 (e.g., quinidine). 7.3 Other Potentially Significant Drug Interactions Monoamine Oxidase Inhibitors Serious adverse reactions such as serotonin syndrome have been reported in patients treated with a SSRI and a concomitant monoamine oxidase inhibitor (MAOI), in patients started on an SSRI who recently received an MAOI and in patients started on an MAOI who recently received an SSRI. Therefore, concomitant use of MAOIs with paroxetine capsules or use of paroxetine capsules and an MAOI within 14 days of each other is contraindicated [see Dosage and Administration ( 2.2 ), Contraindications ( 4.1 ) and Warnings and Precautions ( 5.2 )] . Serotonergic Drugs If concomitant use of paroxetine capsules with other serotonergic drugs (e.g., other SNRIs, SSRIs, triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, and St. John’s Wort) is clinically warranted, consider the increased risk of serotonin syndrome and carefully observe the patient, particularly during treatment initiation [see Warnings and Precautions ( 5.2 )] . An interaction between paroxetine and tryptophan may occur when they are co-administered. Adverse reactions, consisting primarily of headache, nausea, sweating, and dizziness, have been reported when tryptophan was administered to patients taking paroxetine. Consequently, concomitant use of paroxetine capsules with tryptophan is not recommended. Drugs that Interfere with Hemostasis (e.g., NSAIDs, Aspirin, and Warfarin) Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs are concomitantly administered with NSAIDs, aspirin, warfarin or other drugs that affect coagulation. There may be a pharmacodynamic interaction between paroxetine and warfarin that causes an increased bleeding diathesis despite unaltered prothrombin time. Carefully monitor patients receiving warfarin therapy when paroxetine capsules are initiated or discontinued [see Warnings and Precautions ( 5.4 )] .

<table width="540pt"><col width="18%"/><col width="33%"/><col width="49%"/><tbody><tr styleCode="Toprule"><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Concomitant Drug Name</content></paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Effect of Paroxetine on Other Drugs</content></paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Clinical Recommendations</content></paragraph></td></tr><tr styleCode="Toprule"><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Thioridazine </paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Increased plasma concentrations of thioridazine </paragraph><paragraph>Potential QTc prolongation </paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Concomitant use of thioridazine and paroxetine capsules is contraindicated. </paragraph></td></tr><tr styleCode="Toprule"><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Pimozide </paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Increased plasma concentrations of pimozide. Potential QTc prolongation </paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Concomitant use of pimozide and paroxetine capsules is contraindicated. </paragraph></td></tr><tr styleCode="Toprule"><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Tamoxifen </paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Reduced plasma concentrations of active tamoxifen metabolite </paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Consider avoiding concomitant use of tamoxifen and paroxetine capsules. </paragraph></td></tr><tr styleCode="Toprule"><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Tricyclic Antidepressants (TCA) </paragraph><paragraph>(e.g., Desipramine) </paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Increased plasma concentrations and elimination half-life </paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Plasma TCA concentrations may need to be monitored and the TCA dosage may need to be reduced if a TCA is used concomitantly with paroxetine capsules. Monitor tolerability.</paragraph></td></tr><tr styleCode="Toprule"><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Risperidone </paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Increased plasma concentrations of risperidone </paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>A lower risperidone dosage may be necessary (see the risperidone Prescribing Information for). Monitor tolerability.</paragraph></td></tr><tr styleCode="Toprule"><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Atomoxetine </paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Increased exposure of atomoxetine </paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>A lower atomoxetine dosage of may be necessary (see atomoxetine Prescribing Information for).

aragraph>Atomoxetine </paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Increased exposure of atomoxetine </paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>A lower atomoxetine dosage of may be necessary (see atomoxetine Prescribing Information for). Monitor tolerability.</paragraph></td></tr><tr styleCode="Toprule"><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Drugs Highly Bound to Plasma Protein (e.g., Warfarin) </paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Increased free plasma concentrations </paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>The warfarin dosage may need to be reduced. Monitor tolerability and the International Normalized Ratio.</paragraph></td></tr><tr styleCode="Toprule"><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Digoxin </paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Decreased plasma concentrations of digoxin </paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>The digoxin dosage of may need to be increased. Monitor digoxin concentrations and clinical effect.</paragraph></td></tr><tr styleCode="Toprule"><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>Theophylline </paragraph></td><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>Increased plasma concentrations of theophylline </paragraph></td><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>The theophylline dosage of may need to be decreased. Monitor theophylline concentrations and tolerability.</paragraph></td></tr></tbody></table>

e Lrule Toprule " valign="top"><paragraph>Increased plasma concentrations of theophylline </paragraph></td><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>The theophylline dosage of may need to be decreased. Monitor theophylline concentrations and tolerability.</paragraph></td></tr></tbody></table> <table width="540pt"><col width="18%"/><col width="30%"/><col width="52%"/><tbody><tr styleCode="Toprule"><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">Concomitant Drug Name</content></paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">Effect of Concomitant Drug on Paroxetine</content></paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">Clinical Recommendations</content></paragraph></td></tr><tr styleCode="Toprule"><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Phenobarbital </paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Decreased paroxetine exposure </paragraph></td><td rowspan="4" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Monitor clinical effect of paroxetine capsules. </paragraph><paragraph>No paroxetine capsules dosage adjustment is needed.</paragraph></td></tr><tr styleCode="Toprule"><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Phenytoin </paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Decreased paroxetine exposure </paragraph></td></tr><tr styleCode="Toprule"><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Fosamprenavir/ Ritonavir </paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Decreased plasma concentration of paroxetine </paragraph></td></tr><tr styleCode="Toprule"><td styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph>Cimetidine </paragraph></td><td styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph>Increased plasma concentration of paroxetine </paragraph></td></tr></tbody></table>

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Paroxetine capsules are contraindicated in pregnant females and not indicated for use in pre-menopausal females. Based on epidemiologic and animal studies, paroxetine can cause fetal harm. Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions ( 5.4 )] . Paroxetine is associated with a less than 2-fold increase in cardiovascular malformations when administered to a pregnant female during the first trimester. While individual epidemiological studies on the association between paroxetine use and cardiovascular malformations have reported inconsistent findings, some meta-analyses of epidemiological studies have identified an increased risk of cardiovascular malformations (see Data ). There are risks of persistent pulmonary hypertension of the newborn (PPHN) (see Data) and/or poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (SSRIs), including paroxetine capsules, during pregnancy. No evidence of treatment related malformations was observed in animal reproduction studies, when paroxetine was administered during the period of organogenesis at doses up to 50 mg/kg/day in rats and 6 mg/kg/day in rabbits. These doses are approximately 64 times (rat) and less than 16 times (rabbit) the maximum recommended human dose (MRHD) of paroxetine capsules (7.5 mg) on an mg/m 2 basis. When paroxetine was administered to female rats during the last trimester of gestation and continued through lactation, there was an increase in the number of pup deaths during the first four days of lactation. This effect occurred at a dose of 1 mg/kg/day which is 1.3 times the MRHD on an mg/m 2 basis ( see Data ). Data Human Data: Published epidemiological studies on the association between first trimester paroxetine use and cardiovascular malformations have reported inconsistent results; however, meta-analyses of population-based cohort studies published between 1996-2017 indicate a less than 2-fold increased risk for overall cardiovascular malformations. Specific cardiac malformations identified in two meta-analyses include approximately 2 to 2.5-fold increased risk for right ventricular outflow tract defects. One meta-analysis also identified an increased risk (less than 2-fold) for bulbus cordis anomalies and anomalies of cardiac septal closure, and an increased risk for atrial septal defects (pooled OR 2.38, 95% CI 1.14-4.97). Important limitations of the studies included in these meta-analyses include potential confounding by indication, depression severity, and potential exposure misclassification. Exposure to SSRIs, particularly later in pregnancy, may have an increased risk for PPHN. PPHN occurs in 1-2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. Animal Data : Reproduction studies were performed at doses up to 50 mg/kg/day in rats and 6 mg/kg/day in rabbits administered during organogenesis. These doses are approximately 64 times (rat) and less than 16 times (rabbit) MRHD of paroxetine capsules (7.5 mg) on an mg/m 2 basis. These studies have revealed no evidence of malformations.

duction studies were performed at doses up to 50 mg/kg/day in rats and 6 mg/kg/day in rabbits administered during organogenesis. These doses are approximately 64 times (rat) and less than 16 times (rabbit) MRHD of paroxetine capsules (7.5 mg) on an mg/m 2 basis. These studies have revealed no evidence of malformations. However, in rats, there was an increase in pup deaths during the first 4 days of lactation when dosing occurred during the last trimester of gestation and continued throughout lactation. This effect occurred at a dose of 1 mg/kg/day which is 1.3 times the MRHD on an mg/m 2 basis. The no effect dose for rat pup mortality was not determined. The cause of these deaths is not known. 8.4 Pediatric Use Safety and effectiveness of paroxetine capsules in pediatric patients have not been established; paroxetine capsules are not indicated in the pediatric population. 8.5 Geriatric Use Clinical trials of paroxetine capsules did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger adult patients. Patients 65 years of age and older may have elevated paroxetine plasma concentrations compared to younger adult patients. However, the recommended paroxetine capsules dosage in patients 65 years of age and older is that same as that as younger patients [see Clinical Pharmacology ( 12.3 )] . SSRIs have been associated with cases of clinically significant hyponatremia in geriatric patients, who may be at greater risk for this adverse reaction [see Warnings and Precautions ( 5.6 )] . 8.6 Renal Impairment The recommended paroxetine capsules dosage in patients with renal impairment is the same as those with normal renal function [see Clinical Pharmacology ( 12.3 )]. 8.7 Hepatic Impairment The recommended paroxetine capsules dosage in patients with hepatic impairment is the same as those with normal hepatic function [see Clinical Pharmacology ( 12.3 )].

10 OVERDOSAGE The following have been reported with paroxetine tablets overdose: • Seizures, which may be delayed, and altered mental status including coma. • Cardiovascular toxicity, which may be delayed, including QRS and QTc interval prolongation. Hypertension most commonly seen, but rarely can see hypotension alone or with co-ingestants including alcohol. • Serotonin syndrome (patients with a multiple drug overdosage with other pro-serotonergic drugs may have a higher risk). Consider contacting the Poison Help Line (1-800-221-2222) or a medical toxicologist for overdose management recommendations.

11 DESCRIPTION Paroxetine is an orally administered selective serotonin reuptake inhibitor (SSRI) for the treatment of moderate to severe VMS associated with menopause. It is identified chemically as (-)- trans -4R- (4’-fluorophenyl) - 3S - [(3’, 4’-methylenedioxyphenoxy) methyl] piperidine mesylate and has the empirical formula of C 19 H 20 FNO 3 •CH 3 SO 3 H. The molecular weight is 425.5 (329.4 as free base). The structural formula is: The mesylate salt of paroxetine is an odorless, white to off-white crystalline powder, having a melting point range of 148 o to 149 o C and a solubility of more than 1 g/mL in water. Each white opaque capsule contains 9.69 mg of paroxetine mesylate equivalent to 7.5 mg paroxetine base. Inactive ingredients consist of: anhydrous dibasic calcium phosphate, black iron oxide, gelatin, magnesium stearate, potassium hydroxide, propylene glycol, shellac, sodium starch glycolate, and titanium dioxide. Figure 1 structural formula

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Nonclinical studies have shown that paroxetine is an SSRI; paroxetine is not an estrogen. The mechanism of action of paroxetine for the treatment of moderate to severe VMS associated with menopause is unknown. Studies at clinically relevant paroxetine doses in humans have demonstrated that paroxetine blocks the uptake of serotonin into human platelets. Paroxetine is a neuronal serotonin reuptake inhibitor with weak effects on norepinephrine and dopamine neuronal reuptake in vitro. Paroxetine also has low affinity for muscarinic alpha 1 -, alpha 2 -, beta-adrenergic, dopamine (D 2 )-, 5-HT 1 -, 5-HT 2 -, and histamine (H 1 )-receptors. 12.2 Pharmacodynamics The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of paroxetine for the treatment of moderate to severe VMS associated with menopause have not been fully characterized. 12.3 Pharmacokinetics Absorption Paroxetine is completely absorbed after oral dosing. In a study in which healthy postmenopausal females (n=24) received paroxetine capsules 7.5 mg once daily for 14 days, steady-state paroxetine concentrations were achieved by approximately 12 days of dosing for most subjects, although it may take substantially longer in an occasional patient. Peak concentrations were reached at a median of 6 hours (3 to 8 hours range). Steady-state mean values of C max , C min , and AUC 0-last were 13.10 ng/mL (CV 91%), 7.17 ng/mL (CV 99%), and 237 hr * ng/mL (CV 94%), respectively. Steady-state AUC 0-24 values were about 3 times those of AUC 0-inf following a single paroxetine dose, indicating non-linear pharmacokinetics. Steady-state C max values were approximately 5 times greater than those attained after a single paroxetine dose and steady-state exposure based on AUC 0-24 was about 10 times greater than AUC 0-24 after a single dose. The nonlinear kinetics and excess accumulation are due to the fact that CYP2D6, an enzyme that is in part responsible for paroxetine metabolism, is readily saturable. Effect of Food: The effects of food on the bioavailability of paroxetine were studied after administration of another paroxetine product with a dosage higher than paroxetine. AUC was slightly increased (6%) when paroxetine was administered with food and the C max was 29% greater, while the time to reach peak plasma concentration decreased from 6.4 hours post-dosing to 4.9 hours. These changes are not clinically significant [see Dosage and Administration ( 2.1 )] . Distribution Paroxetine distributes throughout the body, including the central nervous system, with only 1% remaining in the plasma. Approximately 95% and 93% of paroxetine is bound to plasma protein at 100 ng/mL and 400 ng/mL, respectively. Paroxetine does not alter the in vitro protein binding of phenytoin or warfarin. Elimination Metabolism: Paroxetine is extensively metabolized after oral administration. The principal metabolites are polar and conjugated products of oxidation and methylation, which are readily cleared. Conjugates with glucuronic acid and sulfate predominate, and major metabolites have been isolated and identified. Data indicate that the metabolites have no more than 1/50 the potency of the parent compound at inhibiting serotonin uptake. The metabolism of paroxetine is accomplished in part by cytochrome CYP2D6.

eared. Conjugates with glucuronic acid and sulfate predominate, and major metabolites have been isolated and identified. Data indicate that the metabolites have no more than 1/50 the potency of the parent compound at inhibiting serotonin uptake. The metabolism of paroxetine is accomplished in part by cytochrome CYP2D6. The role of this enzyme in paroxetine metabolism also suggests potential drug interactions [see Drug Interactions ( 7 )] . At steady state, when the CYP2D6 pathway is essentially saturated, paroxetine clearance is governed by alternative P450 isozymes, which, unlike CYP2D6, show no evidence of saturation. Excretion: Approximately 64% of a 30 mg oral solution of another paroxetine product (four times the recommended paroxetine capsules dosage) was excreted in the urine with 2% as the parent compound and 62% as metabolites over a 10-day post-dosing period. About 36% of the dose was excreted in the feces (probably via the bile), mostly as metabolites and less than 1% as the parent compound over the 10-day post-dosing period. Specific Populations Patients with Renal and Hepatic Impairment: Increased plasma concentrations of paroxetine occur in subjects with renal and hepatic impairment. The mean plasma concentration in patients with creatinine clearance below 30 mL/min was approximately 4 times greater than seen in normal volunteers. Patients with creatinine clearance of 30 to 60 mL/min and patients with hepatic impairment had about a 2-fold increase in plasma concentrations (AUC, C max ) [see Use in Specific Populations ( 8.6 , 8.7 )]. Geriatric Patients: In a multiple-dose study in geriatric patients with another paroxetine product at doses of 20, 30, and 40 mg (1.7, 4, and 5.3, times the maximum recommended paroxetine capsules dosage, respectively), C min concentrations were about 70% to 80% greater than the respective C min concentrations in younger adult subjects [see Use in Specific Populations ( 8.5 )]. Drug Interaction Studies Potential Effect of Paroxetine Capsules on Other Drugs • Drugs Metabolized by CYP3A4: An in vivo drug interaction study involving the concomitant use of paroxetine and terfenadine, a substrate for cytochrome CYP3A4, under steady-state conditions revealed no effect of paroxetine on terfenadine pharmacokinetics. In vitro studies have shown ketoconazole, a potent CYP3A4 inhibitor, to be at least 100 times more potent than paroxetine as an inhibitor of the metabolism of several substrates for CYP3A4, including astemizole, triazolam, and cyclosporine. Based on the assumption that the relationship between paroxetine’s in vitro Ki and its lack of effect on terfenadine’s in vivo clearance predicts its effect on other CYP3A4 substrates, paroxetine’s extent of CYP3A4 inhibition is not likely to be of clinical significance. • Drugs Metabolized by CYP2D6: Many drugs are metabolized by the cytochrome P450 isozyme CYP2D6. Like other agents that are metabolized by CYP2D6, paroxetine may significantly inhibit the activity of this isozyme. In most patients (> 90%), this CYP2D6 isozyme is saturated early during paroxetine dosing. Specific studies investigating the effect of paroxetine on drugs metabolized by CYP2D6 are listed below: o Pimozide: In a controlled study of healthy volunteers, after another paroxetine product was titrated to 60 mg daily (8 times the maximum recommended paroxetine capsules dosage), concomitant use of paroxetine with a single 2 mg dose of pimozide was associated with mean increases in pimozide AUC of 151% and C max of 62%, compared to pimozide administered alone [see Drug Interactions ( 7.1 )] .

etine product was titrated to 60 mg daily (8 times the maximum recommended paroxetine capsules dosage), concomitant use of paroxetine with a single 2 mg dose of pimozide was associated with mean increases in pimozide AUC of 151% and C max of 62%, compared to pimozide administered alone [see Drug Interactions ( 7.1 )] . o Desipramine: In one study, daily dosing of another paroxetine product (20 mg once daily) (2.7 times the recommended paroxetine capsules dosage) under steady-state conditions with a concomitant single dose of desipramine (100 mg) increased desipramine C max , AUC, and T ½ by an average of approximately 2-, 5-, and 3-fold, respectively [see Drug Interactions ( 7.1 )] . o Risperidone: Daily dosing of another paroxetine product at 20 mg in patients stabilized on risperidone (4 to 8 mg/day), a CYP2D6 substrate, increased mean plasma risperidone concentrations approximately 4-fold, decreased 9hydroxyrisperidone concentrations approximately 10%, and increased concentrations of the active moiety (the sum of risperidone plus 9-hydroxyrisperidone) approximately 1.4-fold [see Drug Interactions ( 7.1 )] . o Atomoxetine: The effect of paroxetine on the pharmacokinetics of atomoxetine has been evaluated when both drugs were at steady state. In healthy volunteers who were extensive metabolizers of CYP2D6, 20 mg daily of another paroxetine product was given in combination with 20 mg atomoxetine every 12 hours resulting in increases in steady-state atomoxetine AUC values that were 6-to 8-fold greater and in atomoxetine C max values that were 3-to 4-fold greater than when atomoxetine was given alone [see Drug Interactions ( 7.1 )] . o Digoxin: Mean digoxin AUC at steady state decreased by 15% in the presence of paroxetine [see Drug Interactions ( 7.1 )] . o Beta Blockers: In a study in which propranolol (80 mg twice daily) was dosed orally for 18 days, the steady-state plasma concentrations of propranolol were unaltered during concomitant use with another paroxetine product (30 mg once daily) (4 times the recommended paroxetine capsules dosage) for the final 10 days. The effects of propranolol on paroxetine have not been evaluated. Potential Effect of Other Drugs on Paroxetine Capsules Concomitant use of paroxetine with other drugs that alter CYP enzymes activities including CYP2D6 may affect the plasma concentrations of paroxetine. Specific studies investigating the effect of other drugs on paroxetine are listed below: o Cimetidine: Cimetidine inhibits many cytochrome P450 enzymes. In a study in which another paroxetine product was dosed orally at 30 mg once daily (4 times the recommended paroxetine capsules dosage) for 4 weeks, steady-state plasma concentrations of paroxetine were increased by approximately 50% during concomitant use with oral cimetidine (300 mg three times daily) for the final week [see Drug Interactions ( 7.2 )] . o Phenobarbital: Phenobarbital induces many cytochrome P450 enzymes. When a single oral 30 mg dose of another paroxetine product (4 times the recommended paroxetine capsules dosage) was administered at phenobarbital steady state (100 mg once daily for 14 days), paroxetine AUC and T ½ were reduced (by an average of 25% and 38%, respectively) compared to paroxetine administered alone. The effect of paroxetine on phenobarbital pharmacokinetics was not studied. Because paroxetine exhibits nonlinear pharmacokinetics, the results of this study may not address the case where the two drugs are both being chronically dosed [see Drug Interactions ( 7.2 )] .

tively) compared to paroxetine administered alone. The effect of paroxetine on phenobarbital pharmacokinetics was not studied. Because paroxetine exhibits nonlinear pharmacokinetics, the results of this study may not address the case where the two drugs are both being chronically dosed [see Drug Interactions ( 7.2 )] . o Phenytoin: When a single oral 30 mg dose of another paroxetine product (4 times the recommended paroxetine capsules dosage) was administered at phenytoin steady state (300 mg once daily for 14 days), paroxetine AUC and T ½ were reduced (by an average of 50% and 35%, respectively) compared to paroxetine administered alone. In a separate study, when a single oral 300 mg dose of phenytoin was administered with another paroxetine product (30 mg once daily for 14 days) at paroxetine steady state, phenytoin AUC was slightly reduced (12% on average) compared to phenytoin administered alone. Because both drugs exhibit nonlinear pharmacokinetics, the above studies may not address the case where the two drugs are both being chronically dosed [see Drug Interactions ( 7.2 )] . o Digoxin: A clinical drug interaction study showed that concurrent use of digoxin did not affect paroxetine exposure. Diazepam: A clinical drug interaction study showed that concurrent use of diazepam did not affect paroxetine exposure.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Two-year carcinogenicity studies were conducted in rodents given paroxetine in the diet at 1, 5, and 25 mg/kg/day (mice) and 1, 5, and 20 mg/kg/day (rats). The doses used in these carcinogenicity studies were approximately 16 (mouse) and 26 (rat) times the MHRD for paroxetine for the treatment of moderate to severe VMS associated with menopause. There was a significantly greater number of male rats in the high-dose group with reticulum cell sarcomas (1/100, 0/50, 0/50, and 4/50 for control, low-, middle-, and high-dose groups, respectively) and a significantly increased linear trend across groups for the occurrence of lymphoreticular tumors in male rats. Female rats were not affected. Although there was a dose-related increase in the number of tumors in mice, there was no paroxetine -related increase in the number of mice with tumors. The relevance of these findings to humans is unknown. Mutagenesis Paroxetine produced no genotoxic effect in a battery of 5 in vitro and 2 in vivo assays that included the following: bacterial mutation assay, mouse lymphoma mutation assay, unscheduled DNA synthesis assay, and tests for cytogenetic aberrations in vivo in mouse bone marrow and in vitro in human lymphocytes and in a dominant lethal test in rats.

14 CLINICAL STUDIES The effectiveness of paroxetine capsules as a treatment for moderate to severe vasomotor symptoms (VMS) associated with menopause was established in two Phase 3 randomized, double-blind, placebo-controlled clinical trials in 1,174 postmenopausal females. In these trials, patients must have had a minimum of 7-8 moderate to severe VMS per day at baseline (≥ 50 per week) for 30 days prior to receiving study drug. Patients were randomized to paroxetine capsules 7.5 mg orally once daily or daily placebo: • Trial 1 was a 12-week trial with a total of 606 postmenopausal females (average age 55 years; 65% White, 33% Black or African American, and 2% other races; 10.6% were Hispanic/Latina and 89.4% were not Hispanic/Latina; 18% surgically menopausal and 82% naturally menopausal). • Trial 2 was a 24-week trial with a total of 568 postmenopausal females (average age 54 years; 76% White, 22% Black or African American, and 2% other races; 6.5% were Hispanic/Latina and 93.5% were not Hispanic/Latina; 20% surgically menopausal and 81% naturally menopausal). The co-primary efficacy endpoints for both trials were the reduction from baseline in VMS frequency and VMS severity at Weeks 4 and 12. • Data from Trial 1 showed a statistically significant reduction from baseline in the frequency of moderate to severe VMS at Week 4 and Week 12 and a statistically significant reduction in the severity of moderate to severe VMS at Week 4 in the paroxetine capsules group compared to the placebo group (Table 4). • Data from Trial 2 showed a statistically significant reduction from baseline in the frequency and severity of moderate to severe VMS at Week 4 and Week 12 in the paroxetine capsules group compared to placebo group (Table 5). Table 4: Trial 1: Changes in the Daily Frequency and Daily Severity of VMS at Weeks 4 and 12 in Postmenopausal Females with Moderate to Severe VMS (MITT Population) Frequency Severity Paroxetine Capsules Placebo Paroxetine Capsules Placebo Baseline n 301 305 301 305 Median 10.4 10.4 2.5 2.5 Change from baseline at Week 4 n 289 293 281 289 Median -4.3 -3.1 -0.05 0.00 Treatment Difference * -1.2 -0.05 P -value # <0.01 <0.01 Change from baseline at Week 12 n 264 274 236 253 Median -5.9 -5.0 -0.06 -0.02 Treatment Difference * -0.9 -0.04 P -value # <0.01 0.17 MITT population: all consented and randomized patients with valid baseline daily hot flash diary data who had taken at least 1 dose of study drug and had at least 1 day of on-treatment daily hot flash diary data. * Treatment Difference: the difference between the median changes from baseline. # P -value was obtained from rank-ANCOVA model. Table 5: Trial 2: Changes in the Daily Frequency and Daily Severity of VMS at Weeks 4 and 12 in Postmenopausal Females with Moderate to Severe VMS (MITT Population) Frequency Severity Paroxetine Capsules Placebo Paroxetine Capsules Placebo Baseline n 284 284 284 284 Median 9.9 9.6 2.5 2.5 Change from baseline at Week 4 n 276 274 268 271 Median -3.8 -2.5 -0.04 -0.01 Treatment Difference * -1.3 -0.03 P -value # <0.01 0.04 Change from baseline at Week 12 n 257 244 245 236 Median -5.6 -3.9 -0.05 0.00 Treatment Difference * -1.7 -0.05 P -value # <0.01 <0.01 MITT population: all consented and randomized patients with valid baseline daily hot flash diary data who had taken at least 1 dose of study drug and had at least 1 day of on-treatment daily hot flash diary data.

k 12 n 257 244 245 236 Median -5.6 -3.9 -0.05 0.00 Treatment Difference * -1.7 -0.05 P -value # <0.01 <0.01 MITT population: all consented and randomized patients with valid baseline daily hot flash diary data who had taken at least 1 dose of study drug and had at least 1 day of on-treatment daily hot flash diary data. * Treatment Difference: the difference between the median changes from baseline. # P -value is obtained from rank-ANCOVA model. Persistence of benefit at 24 weeks in Trial 2 was evaluated with a responder analysis where responders were defined as those patients who achieved ≥ 50% reduction from baseline in the frequency of moderate to severe VMS at Week 24. The proportion of patients who achieved a ≥ 50% reduction in the frequency of moderate to severe VMS from baseline to Week 24 was 48% in the paroxetine capsules group and 36% in the placebo group at Week 24.

<table width="98%"><col width="22%"/><col width="21%"/><col width="13%"/><col width="21%"/><col width="24%"/><tbody><tr styleCode="Toprule"><td styleCode="Toprule " valign="top"/><td align="center" colspan="2" styleCode="Toprule " valign="top"><paragraph><content styleCode="bold">Frequency</content></paragraph></td><td align="center" colspan="2" styleCode="Toprule " valign="top"><paragraph><content styleCode="bold">Severity</content></paragraph></td></tr><tr><td styleCode="Botrule " valign="top"/><td align="center" styleCode="Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Paroxetine Capsules</content></paragraph></td><td align="center" styleCode="Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Placebo</content></paragraph></td><td align="center" styleCode="Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Paroxetine Capsules</content></paragraph></td><td align="center" styleCode="Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Placebo</content></paragraph></td></tr><tr><td colspan="5" valign="top"><paragraph><content styleCode="bold">Baseline</content></paragraph></td></tr><tr><td valign="top"><paragraph>n</paragraph></td><td align="center" valign="top"><paragraph>301</paragraph></td><td align="center" valign="top"><paragraph>305</paragraph></td><td align="center" valign="top"><paragraph>301</paragraph></td><td align="center" valign="top"><paragraph>305</paragraph></td></tr><tr><td valign="top"><paragraph>Median</paragraph></td><td align="center" valign="top"><paragraph>10.4</paragraph></td><td align="center" valign="top"><paragraph>10.4</paragraph></td><td align="center" valign="top"><paragraph>2.5</paragraph></td><td align="center" valign="top"><paragraph>2.5</paragraph></td></tr><tr><td colspan="5" valign="top"><paragraph><content styleCode="bold"><content styleCode="italics">Change from baseline at Week 4</content></content></paragraph></td></tr><tr><td valign="top"><paragraph>n</paragraph></td><td align="center" valign="top"><paragraph>289</paragraph></td><td align="center" valign="top"><paragraph>293</paragraph></td><td align="center" valign="top"><paragraph>281</paragraph></td><td align="center" valign="top"><paragraph>289</paragraph></td></tr><tr><td valign="top"><paragraph>Median</paragraph></td><td align="center" valign="top"><paragraph>-4.3</paragraph></td><td align="center" valign="top"><paragraph>-3.1</paragraph></td><td align="center" valign="top"><paragraph>-0.05</paragraph></td><td align="center" valign="top"><paragraph>0.00</paragraph></td></tr><tr><td valign="top"><paragraph>Treatment Difference^*</paragraph></td><td align="center" valign="top"><paragraph>-1.2</paragraph></td><td valign="top"/><td align="center" valign="top"><paragraph>-0.05</paragraph></td><td valign="top"/></tr><tr><td valign="top"><paragraph><content styleCode="italics">P</content>-value^#</paragraph></td><td align="center" valign="top"><paragraph>&lt;0.01</paragraph></td><td valign="top"/><td align="center" valign="top"><paragraph>&lt;0.01</paragraph></td><td valign="top"/></tr><tr><td colspan="5" valign="top"><paragraph><content styleCode="bold"><content styleCode="italics">Change from baseline at Week 12</content></content></paragraph></td></tr><tr><td valign="top"><paragraph>n</paragraph></td><td align="center" valign="top"><paragraph>264</paragraph></td><td align="center" valign="top"><paragraph>274</paragraph></td><td align="center" valign="top">

de="bold"><content styleCode="italics">Change from baseline at Week 12</content></content></paragraph></td></tr><tr><td valign="top"><paragraph>n</paragraph></td><td align="center" valign="top"><paragraph>264</paragraph></td><td align="center" valign="top"><paragraph>274</paragraph></td><td align="center" valign="top"> <paragraph>236</paragraph></td><td align="center" valign="top"><paragraph>253</paragraph></td></tr><tr><td valign="top"><paragraph>Median</paragraph></td><td align="center" valign="top"><paragraph>-5.9</paragraph></td><td align="center" valign="top"><paragraph>-5.0</paragraph></td><td align="center" valign="top"><paragraph>-0.06</paragraph></td><td align="center" valign="top"><paragraph>-0.02</paragraph></td></tr><tr><td valign="top"><paragraph>Treatment Difference^*</paragraph></td><td align="center" valign="top"><paragraph>-0.9</paragraph></td><td valign="top"/><td align="center" valign="top"><paragraph>-0.04</paragraph></td><td valign="top"/></tr><tr><td styleCode="Botrule " valign="top"><paragraph><content styleCode="italics">P</content>-value^#</paragraph></td><td align="center" styleCode="Botrule " valign="top"><paragraph>&lt;0.01</paragraph></td><td styleCode="Botrule " valign="top"/><td align="center" styleCode="Botrule " valign="top"><paragraph>0.17</paragraph></td><td styleCode="Botrule " valign="top"/></tr><tr><td colspan="5" styleCode="Toprule " valign="top"><list listType="unordered"><item><caption> </caption>MITT population: all consented and randomized patients with valid baseline daily hot flash diary data who had taken at least 1 dose of study drug and had at least 1 day of on-treatment daily hot flash diary data. </item></list></td></tr><tr><td colspan="5" valign="top"><paragraph>^* Treatment Difference: the difference between the median changes from baseline.</paragraph></td></tr><tr><td colspan="5" styleCode="Botrule " valign="top"><paragraph><content styleCode="italics">^# P</content>-value was obtained from rank-ANCOVA model. </paragraph></td></tr></tbody></table>

agraph>^* Treatment Difference: the difference between the median changes from baseline.</paragraph></td></tr><tr><td colspan="5" styleCode="Botrule " valign="top"><paragraph><content styleCode="italics">^# P</content>-value was obtained from rank-ANCOVA model. </paragraph></td></tr></tbody></table> <table width="545.4pt"><col width="24%"/><col width="20%"/><col width="12%"/><col width="20%"/><col width="25%"/><tbody><tr><td styleCode="Toprule " valign="top"/><td align="center" colspan="2" styleCode="Toprule " valign="top"><paragraph><content styleCode="bold">Frequency</content></paragraph></td><td align="center" colspan="2" styleCode="Toprule " valign="top"><paragraph><content styleCode="bold">Severity</content></paragraph></td></tr><tr><td styleCode="Botrule " valign="top"/><td align="center" styleCode="Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Paroxetine Capsules</content></paragraph></td><td align="center" styleCode="Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Placebo</content></paragraph></td><td align="center" styleCode="Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Paroxetine Capsules</content></paragraph></td><td align="center" styleCode="Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Placebo</content></paragraph></td></tr><tr><td colspan="5" valign="top"><paragraph><content styleCode="bold">Baseline</content></paragraph></td></tr><tr><td valign="top"><paragraph>n</paragraph></td><td align="center" valign="top"><paragraph>284</paragraph></td><td align="center" valign="top"><paragraph>284</paragraph></td><td align="center" valign="top"><paragraph>284</paragraph></td><td align="center" valign="top"><paragraph>284</paragraph></td></tr><tr><td valign="top"><paragraph>Median</paragraph></td><td align="center" valign="top"><paragraph>9.9</paragraph></td><td align="center" valign="top"><paragraph>9.6</paragraph></td><td align="center" valign="top"><paragraph>2.5</paragraph></td><td align="center" valign="top"><paragraph>2.5</paragraph></td></tr><tr><td colspan="5" valign="top"><paragraph><content styleCode="bold"><content styleCode="italics">Change from baseline at Week 4</content></content></paragraph></td></tr><tr><td valign="top"><paragraph>n</paragraph></td><td align="center" valign="top"><paragraph>276</paragraph></td><td align="center" valign="top"><paragraph>274</paragraph></td><td align="center" valign="top"><paragraph>268</paragraph></td><td align="center" valign="top"><paragraph>271</paragraph></td></tr><tr><td valign="top"><paragraph>Median</paragraph></td><td align="center" valign="top"><paragraph>-3.8</paragraph></td><td align="center" valign="top"><paragraph>-2.5</paragraph></td><td align="center" valign="top"><paragraph>-0.04</paragraph></td><td align="center" valign="top"><paragraph>-0.01</paragraph></td></tr><tr><td valign="top"><paragraph>Treatment Difference^*</paragraph></td><td align="center" valign="top"><paragraph>-1.3</paragraph></td><td valign="top"/><td align="center" valign="top"><paragraph>-0.03</paragraph></td><td valign="top"/></tr><tr><td valign="top"><paragraph><content styleCode="italics">P</content>-value^#</paragraph></td><td align="center" valign="top"><paragraph>&lt;0.01</paragraph></td><td valign="top"/><td align="center" valign="top"><paragraph>0.04</paragraph></td><td valign="top"/></tr><tr><td colspan="5" valign="top"><paragraph><content styleCode="bold"><content styleCode="italics">Change from baseline at Week 12</content></content></paragraph></td></tr><tr><td valign="top"><paragraph>n</paragraph></td><td align="center" valign="top"><paragraph>257</paragraph></td><td align="center" valign="top"><paragraph>244</paragraph></td><td align="center" valign="top"><paragraph>245</parag

yleCode="italics">Change from baseline at Week 12</content></content></paragraph></td></tr><tr><td valign="top"><paragraph>n</paragraph></td><td align="center" valign="top"><paragraph>257</paragraph></td><td align="center" valign="top"><paragraph>244</paragraph></td><td align="center" valign="top"><paragraph>245</parag raph></td><td align="center" valign="top"><paragraph>236</paragraph></td></tr><tr><td valign="top"><paragraph>Median</paragraph></td><td align="center" valign="top"><paragraph>-5.6</paragraph></td><td align="center" valign="top"><paragraph>-3.9</paragraph></td><td align="center" valign="top"><paragraph>-0.05</paragraph></td><td align="center" valign="top"><paragraph>0.00</paragraph></td></tr><tr><td valign="top"><paragraph>Treatment Difference^*</paragraph></td><td align="center" valign="top"><paragraph>-1.7</paragraph></td><td valign="top"/><td align="center" valign="top"><paragraph>-0.05</paragraph></td><td valign="top"/></tr><tr><td styleCode="Botrule " valign="top"><paragraph><content styleCode="italics">P</content>-value^#</paragraph></td><td align="center" styleCode="Botrule " valign="top"><paragraph>&lt;0.01</paragraph></td><td styleCode="Botrule " valign="top"/><td align="center" styleCode="Botrule " valign="top"><paragraph>&lt;0.01</paragraph></td><td styleCode="Botrule " valign="top"/></tr><tr><td colspan="5" styleCode="Toprule " valign="top"><list listType="unordered"><item><caption> </caption>MITT population: all consented and randomized patients with valid baseline daily hot flash diary data who had taken at least 1 dose of study drug and had at least 1 day of on-treatment daily hot flash diary data. </item></list></td></tr><tr><td colspan="5" valign="top"><paragraph>^* Treatment Difference: the difference between the median changes from baseline.</paragraph></td></tr><tr><td colspan="5" styleCode="Botrule " valign="top"><paragraph><content styleCode="italics">^# P</content>-value is obtained from rank-ANCOVA model. </paragraph></td></tr></tbody></table>

16 HOW SUPPLIED/STORAGE AND HANDLING Paroxetine capsules are available as 7.5 mg white opaque capsules printed with “544” in black ink on the cap and “7.5 mg” in black ink on the body. NDC 43547-409-03, bottle of 30 Store at 20 o C to 25 o C (68 o F to 77 o F); excursions permitted to 15 o C to 30 o C (59 o F to 86 o F) [See USP Controlled Room Temperature]. Protect from light and humidity.

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Instruct patients to read the Medication Guide before starting therapy with paroxetine capsules and to reread it each time the prescription is renewed. Suicidal Thoughts and Behaviors Advise patients, their families, and their caregivers to look for the emergence of suicidal thoughts and behaviors, especially early during treatment and to alert the health care provider if such changes occur [see Boxed Warning and Warnings and Precautions ( 5.1 )] . Serotonin Syndrome Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of paroxetine capsules with triptans, tricyclic antidepressants, opioids, linezolid, tramadol, amphetamines, St. John’s Wort, lithium, tryptophan supplements, other serotonergic agents, or antipsychotic drugs. Instruct patients to contact their health care provider, or report to the emergency room, should they experience signs or symptoms of serotonin syndrome [see Warnings and Precautions ( 5.2 ) and Drug Interactions ( 7.3 )] . Potential Impact on Tamoxifen Efficacy Caution patients that efficacy of tamoxifen may be reduced when administered concomitantly and counsel them about the likely benefit of paroxetine for treating VMS vs. the risk of possible decreased tamoxifen effectiveness [see Warnings and Precautions ( 5.3 )] . Increased Risk of Bleeding Caution patients about the concomitant use of paroxetine capsules and NSAIDs, aspirin, warfarin, and other anticoagulants because combined use of drugs that interfere with serotonin reuptake has been associated with an increased risk of bleeding [see Warnings and Precautions ( 5.4 )] . Angle-Closure Claucoma Advise patients that taking paroxetine capsules can cause mild pupillary dilation, which in susceptible individuals, can lead to an episode of angle-closure glaucoma existing [See Warnings and Precautions ( 5.5 )] . Hyponatremia Caution patients about the risk of hyponatremia, particularly elderly patients and those who are taking diuretics or are volume-depleted [see Warnings and Precautions ( 5.6 )] . Bone Fracture Inform patients that there is the possibility for an increased risk of fracture [see Warnings and Precautions ( 5.7 )] . Screening Patients for Bipolar Disorder and Monitoring for Mania/Hypomania Advise patients, their families, and their caregivers to observe for signs of activation of mania/hypomania [see Warnings and Precautions ( 5.8 )] . Pregnancy Advise patients to notify their physician if they become pregnant during therapy [see Contraindications ( 4.5 ) and Use in Specific Populations ( 8.1 )] . Drug Interactions Advise patients to inform their healthcare provider if they are taking, or plan to take, any prescription or over-the-counter drugs, including herbal supplements, because there is a potential for interaction with paroxetine [see Drug Interactions ( 7 )] . Sexual Dysfunction Advise patients that use of paroxetine capsules may cause symptoms of sexual dysfunction in female patients. Inform patients that they should discuss any changes in sexual function and potential management strategies with their healthcare provider [see Warnings and Precautions ( 5.10 )]. Allergic Reactions Advise patients to seek medical attention if they develop an allergic reaction such as rash, hives, swelling, or difficulty breathing [see Adverse Reactions ( 6.2 )] .

hanges in sexual function and potential management strategies with their healthcare provider [see Warnings and Precautions ( 5.10 )]. Allergic Reactions Advise patients to seek medical attention if they develop an allergic reaction such as rash, hives, swelling, or difficulty breathing [see Adverse Reactions ( 6.2 )] . Distributed by: Solco Healthcare US, LLC Somerset, NJ 08873, USA Manufactured by: Zhejiang Huahai Pharmaceutical Co., Ltd. Xunqiao, Linhai, Zhejiang, 317024, China Revised: 12/2025 200468-04

MEDICATION GUIDE MEDICATION GUIDE Paroxetine Capsules (PA-rox-eh-tine) Read this Medication Guide that comes with paroxetine capsules before you start taking it and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. Talk with your healthcare provider if there is something you do not understand or want to learn more about. What is the most important information I should know about paroxetine capsules? Paroxetine capsules may cause serious side effects, including: • Increased risk of suicidal thoughts or actions. Paroxetine capsules and related antidepressant medicines may increase suicidal thoughts or actions within the first few months of treatment. o Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions. o Watch for these changes and call your healthcare provider right away if you notice: ▪ New or sudden changes in mood, behavior, actions, thoughts, or feelings, especially if severe. ▪ Pay close attention to any changes when paroxetine capsules are started. o Keep all follow-up visits with your healthcare provider and call between visits if you are worried about symptoms. Call your healthcare provider right away or go to the nearest emergency room if you have any of the following symptoms, especially if they are new, worse, or worry you: o attempts to commit suicide o acting on dangerous impulses o acting aggressive or violent o thoughts about suicide or dying o new or worse depression o new or worse anxiety or panic attacks o feeling agitated, restless, angry or irritable o trouble sleeping o an increase in activity or talking more than what is normal for you o other unusual changes in behavior or mood. What are paroxetine capsules? • Paroxetine capsules are prescription medicine used to treat moderate to severe hot flashes associated with menopause. • Paroxetine capsules are not any for psychiatric problems such as depression, obsessive compulsive disorder, panic disorder, generalized anxiety disorder, social anxiety disorder, and post-traumatic stress disorder. • Paroxetine capsules are not for use in children. Who should not take paroxetine capsules? Do not take paroxetine capsules if you: • take a Monoamine Oxidase Inhibitor (MAOI). Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid or the intravenous methylene blue. o Do not take an MAOI within 14 days of stopping paroxetine capsules unless directed to do so by your healthcare provider. o Do not start paroxetine capsules if you stopped taking an MAOI in the last 14 days unless directed to do so by your healthcare provider. o People who take paroxetine capsules close in time to an MAOI may have a serious or life-threatening side effect called serotonin syndrome. Get medical help right away if you have any of these symptoms: ▪ high fever ▪ uncontrolled muscle spasms ▪ stiff muscles ▪ rapid changes in heart rate or blood pressure ▪ confusion ▪ loss of consciousness (pass out) ▪ nausea, vomiting, or diarrhea • take thioridazine. Do not take thioridazine together with paroxetine capsules because this can cause serious heart rhythm problems or sudden death. • take the antipsychotic medicine pimozide. Do not take pimozide together with paroxetine capsules because this can cause serious heart problems.

a, vomiting, or diarrhea • take thioridazine. Do not take thioridazine together with paroxetine capsules because this can cause serious heart rhythm problems or sudden death. • take the antipsychotic medicine pimozide. Do not take pimozide together with paroxetine capsules because this can cause serious heart problems. • are allergic to paroxetine or any of the ingredients in paroxetine capsules. See the end of this Medication Guide for a complete list of ingredients in paroxetine capsules. • are pregnant or become pregnant. Paroxetine capsules can harm your unborn baby. Call your healthcare provider if you become pregnant while taking paroxetine capsules. What should I tell my healthcare provider before taking paroxetine capsules? Before taking paroxetine capsules, tell your healthcare provider about all of your medical conditions, including if you: • have liver problems • have kidney problems • have or had seizures or convulsions • have or have a family history of bipolar disorder, mania or hypomania • have low sodium levels in your blood • have or had bleeding problems • have glaucoma (high pressure in the eye) • have bone problems Tell your healthcare provider about all the medicines that you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements. Paroxetine capsules and some medicines may interact with each other, may not work as well, or may cause serious side effects when taken together. If you take paroxetine capsules, you should not take any other medicines that contain paroxetine, including Paxil, Paxil CR and Pexeva. Especially tell your healthcare provider if you take: • triptans used to treat migraine headache • medicines used to treat mood, anxiety, psychotic or thought disorders, including MAOIs, SSRIs, tricyclics, lithium, buspirone, or antipsychotics • tramadol, fentanyl, meperidine, methadone, or other opioids • over-the-counter supplements such as tryptophan or St. John’s Wort • amphetamines • thioridazine • pimozide • tamoxifen • atomoxetine • cimetidine • digoxin • theophylline • medicines to treat irregular heart rate (like propafenone, flecainide, and encainide) • medicines used to treat schizophrenia • certain medicines used to treat HIV infection • the blood thinner warfarin • nonsteroidal anti-inflammatory drugs (NSAIDs) (like ibuprofen, naproxen, or aspirin) • certain medicines used to treat seizures (like phenobarbital and phenytoin) • other drugs containing paroxetine, the medicine in paroxetine capsules. Ask your healthcare provider if you are not sure if you are taking any of these medications. Your healthcare provider or pharmacist can tell you if it is safe to take paroxetine capsules with your other medicines. Do not start or stop any medicine while taking paroxetine capsules without talking to your healthcare provider first. How should I take paroxetine capsules? • Take paroxetine capsules exactly as your healthcare provider tells you to take it. • Take paroxetine capsules 1 time each day at bedtime. • Paroxetine capsules may be taken with or without food. • If you take too many paroxetine capsules, call your healthcare provider or Poison Help line right away, or go to the nearest emergency room right away. What are the possible side effects of paroxetine capsules? Paroxetine capsules may cause serious side effects, including: • See “What is the most important information I should know about paroxetine capsules?” • Serotonin syndrome. This condition can be life-threatening and can happen when you take paroxetine capsules with certain other medicines.

fects of paroxetine capsules? Paroxetine capsules may cause serious side effects, including: • See “What is the most important information I should know about paroxetine capsules?” • Serotonin syndrome. This condition can be life-threatening and can happen when you take paroxetine capsules with certain other medicines. Call your healthcare provider or go to the nearest hospital emergency room right away if you have any of the following symptoms of serotonin syndrome: o agitation (nervousness), hallucinations, coma or other changes in mental status o coordination problems or muscle twitching (small movements of the muscles that you cannot control) o racing heartbeat, high or low blood pressure o sweating or fever o nausea, vomiting, or diarrhea o muscle rigidity o dizziness o flushing o tremors o seizures • Reduced effectiveness of tamoxifen. Tamoxifen (a medicine used to treat breast cancer) may not work as well if it is taken while you take paroxetine capsules. If you are taking tamoxifen, tell your healthcare provider before starting paroxetine capsules. • Abnormal bleeding. Paroxetine capsules may increase your risk of bleeding or bruising, especially if you take the blood thinner warfarin or non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, naproxen, or aspirin. • Visual problems (angle-closure glaucoma). Paroxetine capsules may cause a visual problem called angle-closure glaucoma. Symptoms may include: o eye pain o changes in vision o swelling or redness in or around the eye Only some people are at risk for these problems. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are. • Low salt (sodium) levels in the blood . Elderly people and those taking diuretics or are dehydrated are at greater risk of experiencing low salt levels in their blood. Symptoms may include: o headache o weakness or feeling unsteady o confusion, problems concentrating or thinking or memory problems o seeing or hearing things that are not there (hallucinations) o fainting (syncope) o seizures o stopping breathing (respiratory arrest) • Bone fractures. Women who take paroxetine capsules may have a higher risk of bone fractures. Contact your healthcare provider if you have pain in a bone. • Manic episodes. Manic episodes may happen in people with bipolar disorder who take paroxetine capsules. Symptoms may include: o greatly increased energy o severe trouble sleeping o racing thoughts o reckless behavior o unusually grand ideas o excessive happiness or irritability o talking more or faster than usual • Seizures • Sexual problems (dysfunction). Taking selective serotonin reuptake inhibitors (SSRIs), including paroxetine capsules, may cause symptoms of sexual problems. Symptoms in females may include: o decreased sexual drive o delayed or inability to have an orgasm The most common side effects of paroxetine capsules include: • headache • tiredness • nausea and vomiting Tell your healthcare provider if you have any side effect that bothers you or does not go away. These are not all the possible side effects of paroxetine capsules. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store paroxetine capsules? • Store paroxetine capsules at room temperature between 68℉ to 77℉ (20℃ to 25℃). • Keep paroxetine capsules out of the light. • Keep paroxetine capsules dry. Keep paroxetine capsules and all medicines out of the reach of children. General information about the safe and effective use of paroxetine capsules. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide.

Keep paroxetine capsules out of the light. • Keep paroxetine capsules dry. Keep paroxetine capsules and all medicines out of the reach of children. General information about the safe and effective use of paroxetine capsules. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use paroxetine capsules for a condition for which it was not prescribed. Do not give paroxetine capsules to other people, even if they have the same condition. It may harm them. You may ask your healthcare provider or pharmacist for information about paroxetine capsules that are written for healthcare professionals. What are the ingredients in paroxetine capsules? Active ingredient: paroxetine Inactive ingredients: anhydrous dibasic calcium phosphate, black iron oxide, gelatin, magnesium stearate, potassium hydroxide, propylene glycol, shellac, sodium starch glycolate, and titanium dioxide. Distributed by: Solco Healthcare US, LLC Somerset, NJ 08873, USA Manufactured by: Zhejiang Huahai Pharmaceutical Co., Ltd. Xunqiao, Linhai, Zhejiang, 317024, China For more information about paroxetine capsules, call Solco Healthcare US, LLC at 1-866-257-2597. This Medication Guide has been approved by the U.S. Food and Drug Administration Revised: 12/2025

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors [see Warnings and Precautions (5.1) ]. Paroxetine is not approved for use in pediatric patients [see Use in Specific Populations (8.4) ]. WARNING: SUICIDAL THOUGHTS AND BEHAVIORS See full prescribing information for complete boxed warning. Increased risk of suicidal thoughts and behavior in pediatric and young adult patients taking antidepressants. Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors. Paroxetine is not approved for use in pediatric patients. (5.1 , 8.4)

1 INDICATIONS AND USAGE Paroxetine tablets are indicated in adults for the treatment of: Major depressive disorder (MDD) Obsessive compulsive disorder (OCD) Panic disorder (PD) Social anxiety disorder (SAD) Generalized anxiety disorder (GAD) Posttraumatic stress disorder (PTSD) Paroxetine is a selective serotonin reuptake inhibitor (SSRI) indicated in adults for the treatment of (1) : Major Depressive Disorder (MDD) Obsessive Compulsive Disorder (OCD) Panic Disorder (PD) Social Anxiety Disorder (SAD) Generalized Anxiety Disorder (GAD) Posttraumatic Stress Disorder (PTSD)

2 DOSAGE AND ADMINISTRATION Recommended starting and maximum daily dosage for MDD, OCD, PD, and PTSD: (2.2) Indication Starting Daily Dose Maximum Daily Dose MDD 20 mg 50 mg OCD 20 mg 60 mg PD 10 mg 60 mg PTSD 20 mg 50 mg Recommended starting dosage for SAD and GAD is 20 mg daily. (2.3) Elderly patients, patients with severe renal impairment or severe hepatic impairment: Starting dosage is 10 mg daily. Maximum dosage is 40 mg daily. (2.4) When discontinuing paroxetine tablets, reduce dosage gradually. (2.6 , 5.7) 2.1 Administration Information Administer paroxetine tablets as a single daily dose in the morning, with or without food. 2.2 Recommended Dosage for MDD, OCD, PD, and PTSD The recommended starting dosages and maximum dosages of paroxetine tablets in patients with MDD, OCD, PD, and PTSD are presented in Table 1. In patients with an inadequate response, increase dosage in increments of 10 mg per day at intervals of at least 1 week, depending on tolerability. Table 1 Recommended Daily Dosage of Paroxetine Tablets in Patients with MDD, OCD, PD, and PTSD Indication Starting Dose Maximum Dose MDD 20 mg 50 mg OCD 20 mg 60 mg PD 10 mg 60 mg PTSD 20 mg 50 mg 2.3 Recommended Dosage for SAD and GAD SAD The starting and recommended dosage in patients with SAD is 20 mg daily. In clinical trials the effectiveness of paroxetine tablets was demonstrated in patients dosed in a range of 20 mg to 60 mg daily. While the safety of paroxetine tablets has been evaluated in patients with SAD at doses up to 60 mg daily, available information does not suggest any additional benefit for doses above 20 mg daily [see Clinical Studies (14.4) ]. GAD The starting and recommended dosage in patients with GAD is 20 mg daily. In clinical trials the effectiveness of paroxetine tablets in GAD was demonstrated in patients dosed in a range of 20 mg to 50 mg daily. There is not sufficient evidence to suggest a greater benefit to doses higher than 20 mg daily [see Clinical Studies (14.5) ]. In patients with an inadequate response, increase dosage in increments of 10 mg per day at intervals of at least 1 week, depending on tolerability. 2.4 Screen for Bipolar Disorder Prior to Starting Paroxetine Tablets Prior to initiating treatment with paroxetine tablets or another antidepressant, screen patients for a personal or family history of bipolar disorder, mania, or hypomania [see Warnings and Precautions (5.6) ]. 2.5 Recommended Dosage for Elderly Patients, Patients with Severe Renal Impairment, and Patients with Severe Hepatic Impairment The recommended initial dosage is 10 mg per day for elderly patients, patients with severe renal impairment, and patients with severe hepatic impairment. Dosage should not exceed 40 mg/day. 2.6 Switching Patients to or From a Monoamine Oxidase Inhibitor (MAOI) At least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI and initiation of paroxetine tablets. In addition, at least 14 days must elapse after stopping paroxetine before starting an MAOI antidepressant [see Contraindications (4) , Warnings and Precautions (5.2) ]. 2.7 Discontinuation of Treatment With Paroxetine Tablets Adverse reactions may occur upon discontinuation of paroxetine tablets [see Warnings and Precautions (5.7) ]. Gradually reduce the dosage rather than stopping paroxetine abruptly whenever possible.

3 DOSAGE FORMS AND STRENGTHS Paroxetine tablets, USP are available as: 10 mg: White to off-white, round-shaped, biconvex, film-coated tablets debossed with the logo of 'ZC, 15 and bisect' on one side and plain on other side 20 mg: White to off-white, round-shaped, biconvex, film-coated tablets debossed with the logo of 'ZC, 16 and bisect' on one side and plain on other side 30 mg: White to off-white, round-shaped, biconvex, film-coated tablets debossed with the logo of 'ZC17' on one side and plain on other side 40 mg: White to off-white, round-shaped, biconvex, film-coated tablets debossed with the logo of 'ZC18' on one side and plain on other side Tablets: 10 mg, scored; 20 mg, scored; 30 mg; and 40 mg tablets. (3)

4 CONTRAINDICATIONS Paroxetine tablets are contraindicated in patients: Taking, or within 14 days of stopping, MAOIs (including the MAOIs linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [see Warnings and Precautions (5.2) , Drug Interactions (7) ]. Taking thioridazine because of risk of QT prolongation [see Warnings and Precautions (5.3) and Drug Interactions (7) ]. Taking pimozide because of risk of QT prolongation [see Warnings and Precautions (5.3) , Drug Interactions (7) ]. With known hypersensitivity (e.g., anaphylaxis, angioedema, Stevens-Johnson syndrome) to paroxetine or any of the inactive ingredients in paroxetine tablets [see Adverse Reactions (6.1) , (6.2) ]. Concomitant use of monoamine oxidase inhibitors (MAOIs) or use within 14 days of discontinuing a MAOI. (4 , 5.3 , 7) Concomitant use of pimozide or thioridazine. (4 , 5.3 , 7) Known hypersensitivity to paroxetine or to any of the inactive ingredients in paroxetine tablets. (4)

5 WARNINGS AND PRECAUTIONS Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents, but also when taken alone. If occurs, discontinue paroxetine and serotonergic agents and initiate supportive measures. (5.2) Embryofetal Toxicity: May cause fetal harm. Meta-analyses of epidemiological studies have shown increased risk (less than 2-fold) of cardiovascular malformations with exposure during the first trimester. (5.4 , 8.1) Increased Risk of Bleeding: Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, other antiplatelet drugs, warfarin, and other anticoagulant drugs may increase risk. (5.5) Activation of Mania/Hypomania: Screen patients for bipolar disorder. (5.6) Seizures: Use with caution in patients with seizure disorders. (5.8) Angle-Closure Glaucoma: Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants. (5.9) Sexual Dysfunction: paroxetine may cause symptoms of sexual dysfunction. (5.13) 5.1 Suicidal Thoughts and Behaviors in Adolescents and Young Adults In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater than in placebo-treated patients. There was considerable variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied. There were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with MDD. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1,000 patients treated are provided in Table 2. Table 2 Risk Differences of the Number of Patients with Suicidal Thoughts and Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients Age Range Drug-Placebo Difference in Number of Patients with Suicidal Thoughts and Behaviors per 1,000 Patients Treated Increases Compared to Placebo < 18 years old 14 additional cases 18 years to 24 years old 5 additional cases Decreases Compared to Placebo 25 years to 64 years old 1 fewer case ≥ 65 years old 6 fewer cases Paroxetine is not approved for use in pediatric patients. It is unknown whether the risk of suicidal thoughts and behaviors in children, adolescents, and young adults extends to longer-term use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with MDD that antidepressants delay the recurrence of depression and that depression itself is a risk factor for suicidal thoughts and behaviors. Monitor all antidepressant-treated patients for any indication for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy, and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing paroxetine, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.

l family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing paroxetine, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors. 5.2 Serotonin Syndrome SSRIs, including paroxetine, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines and St. John's Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [see Contraindications (4) , Drug Interactions (7) ]. Serotonin syndrome can also occur when these drugs are used alone. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The concomitant use of paroxetine with MAOIs is contraindicated. In addition, do not initiate paroxetine in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection) or at lower doses. If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking paroxetine discontinue paroxetine before initiating treatment with the MAOI [see Contraindications (4) , Drug Interactions (7) ]. Monitor all patients taking paroxetine for the emergence of serotonin syndrome. Discontinue treatment with paroxetine and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of paroxetine with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms. 5.3 Drug Interactions Leading to QT Prolongation The CYP2D6 inhibitory properties of paroxetine can elevate plasma levels of thioridazine and pimozide. Since thioridazine and pimozide given alone produce prolongation of the QTc interval and increase the risk of serious ventricular arrhythmias, the use of paroxetine is contraindicated in combination with thioridazine and pimozide [see Contraindications (4) , Drug Interactions (7) , Clinical Pharmacology (12.3) ]. 5.4 Embryofetal Toxicity Based on meta-analyses of epidemiological studies, exposure to paroxetine in the first trimester of pregnancy is associated with a less than 2-fold increase in the rate of cardiovascular malformations among infants. For women who intend to become pregnant or who are in their first trimester of pregnancy, paroxetine, should be initiated only after consideration of the other available treatment options [see Use in Specific Populations (8.1) ]. 5.5 Increased Risk of Bleeding Drugs that interfere with serotonin reuptake inhibition, including paroxetine, increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDS), other antiplatelet drugs, warfarin, and other anticoagulants may add to this risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding.

atory drugs (NSAIDS), other antiplatelet drugs, warfarin, and other anticoagulants may add to this risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Based on data from the published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Use in Specific Populations (8.1) ]. Bleeding events related to drugs that interfere with serotonin reuptake have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages. Inform patients about the increased risk of bleeding associated with the concomitant use of paroxetine and antiplatelet agents or anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio. 5.6 Activation of Mania or Hypomania In patients with bipolar disorder, treating a depressive episode with paroxetine or another antidepressant may precipitate a mixed/manic episode. During controlled clinical trials of paroxetine, hypomania or mania occurred in approximately 1% of paroxetine-treated unipolar patients compared to 1.1% of active-control and 0.3% of placebo-treated unipolar patients. Prior to initiating treatment with paroxetine, screen patients for any personal or family history of bipolar disorder, mania, or hypomania. 5.7 Discontinuation Syndrome Adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt discontinuation, include: nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia, such as electric shock sensations), tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible [see Dosage and Administration (2.7) ]. During clinical trials of GAD and PTSD, gradual decreases in the daily dose by 10 mg/day at weekly intervals followed by 1 week at 20 mg/day was used before treatment was discontinued. The following adverse reactions were reported at an incidence of 2% or greater for paroxetine and were at least twice that reported for placebo: Abnormal dreams, paresthesia, and dizziness. Adverse reactions have been reported upon discontinuation of treatment with paroxetine in pediatric patients. The safety and effectiveness of paroxetine in pediatric patients have not been established [see Boxed Warning , Warnings and Precautions (5.1) , Use in Specific Populations (8.4) ]. 5.8 Seizures Paroxetine tablets have not been systematically evaluated in patients with seizure disorders. Patients with history of seizures were excluded from clinical studies. During clinical studies, seizures occurred in 0.1% of patients treated with paroxetine. Paroxetine should be prescribed with caution in patients with a seizure disorder. Discontinue paroxetine in any patient who develops seizures. 5.9 Angle-Closure Glaucoma The pupillary dilation that occurs following use of many antidepressant drugs including paroxetine may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy. Cases of angle-closure glaucoma associated with use of paroxetine have been reported. Avoid use of antidepressants, including paroxetine in patients with untreated anatomically narrow angles. 5.10 Hyponatremia Hyponatremia may occur as a result of treatment with SSRIs, including paroxetine. Cases with serum sodium lower than 110 mmol/L have been reported.

iated with use of paroxetine have been reported. Avoid use of antidepressants, including paroxetine in patients with untreated anatomically narrow angles. 5.10 Hyponatremia Hyponatremia may occur as a result of treatment with SSRIs, including paroxetine. Cases with serum sodium lower than 110 mmol/L have been reported. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls. Signs and symptoms associated with more severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). In patients with symptomatic hyponatremia, discontinue paroxetine and institute appropriate medical intervention. Elderly patients, patients taking diuretics, and those who are volume-depleted may be at greater risk of developing hyponatremia with SSRIs [see Use in Specific Populations (8.5) ]. 5.11 Reduction of Efficacy of Tamoxifen Some studies have shown that the efficacy of tamoxifen, as measured by the risk of breast cancer relapse/mortality, may be reduced with concomitant use of paroxetine as a result of paroxetine's irreversible inhibition of CYP2D6 and lower blood levels of tamoxifen [see Drug Interactions (7) ]. One study suggests that the risk may increase with longer duration of co-administration. However, other studies have failed to demonstrate such a risk. When tamoxifen is used for the treatment or prevention of breast cancer, prescribers should consider using an alternative antidepressant with little or no CYP2D6 inhibition. 5.12 Bone Fracture Epidemiological studies on bone fracture risk during exposure to some antidepressants, including SSRIs, have reported an association between antidepressant treatment and fractures. There are multiple possible causes for this observation and it is unknown to what extent fracture risk is directly attributable to SSRI treatment. 5.13 Sexual Dysfunction Use of SSRIs, including paroxetine, may cause symptoms of sexual dysfunction [see Adverse Reactions (6.1) ]. In male patients, SSRI use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction. In female patients, SSRI use may result in decreased libido and delayed or absent orgasm. It is important for prescribers to inquire about sexual function prior to initiation of paroxetine and to inquire specifically about changes in sexual function during treatment, because sexual function may not be spontaneously reported. When evaluating changes in sexual function, obtaining a detailed history (including timing of symptom onset) is important because sexual symptoms may have other causes, including the underlying psychiatric disorder. Discuss potential management strategies to support patients in making informed decisions about treatment.

<table ID="_RefID622" width="100%"><caption>Table 2 Risk Differences of the Number of Patients with Suicidal Thoughts and Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients</caption><col width="35%"/><col width="65%"/><tbody><tr><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">Age Range</content></paragraph></td><td align="center" styleCode="Rrule Botrule Toprule " valign="middle"><paragraph><content styleCode="bold">Drug-Placebo Difference in Number of Patients with Suicidal Thoughts and Behaviors per 1,000 Patients Treated</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"/><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">Increases Compared to Placebo</content></paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>&lt; 18 years old</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>14 additional cases</paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>18 years to 24 years old</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>5 additional cases</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"/><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">Decreases Compared to Placebo</content></paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>25 years to 64 years old</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1 fewer case</paragraph></td></tr><tr><td align="center" styleCode="Rrule Botrule Lrule " valign="middle"><paragraph>&#x2265; 65 years old</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>6 fewer cases</paragraph></td></tr></tbody></table>

6 ADVERSE REACTIONS The following adverse reactions are included in more detail in other sections of the prescribing information: Hypersensitivity reactions to paroxetine [see Contraindications (4) ] Suicidal Thoughts and Behaviors [see Warnings and Precautions (5.1) ] Serotonin Syndrome [see Warnings and Precautions (5.2) ] Embryofetal Toxicity [see Warnings and Precautions (5.4) ] Increased Risk of Bleeding [see Warnings and Precautions (5.5) ] Activation of Mania/Hypomania [see Warnings and Precautions (5.6) ] Discontinuation Syndrome [see Warnings and Precautions (5.7) ] Seizures [see Warnings and Precautions (5.8) ] Angle-closure Glaucoma [see Warnings and Precautions (5.9) ] Hyponatremia [see Warnings and Precautions (5.10) ] Bone Fracture [see Warnings and Precautions (5.12) ] Sexual Dysfunction [see Warnings and Precautions (5.13) ] Most common adverse reactions (≥ 5% and at least twice placebo) are abnormal ejaculation, asthenia, constipation, decreased appetite, diarrhea, dizziness, dry mouth, female genital disorder, impotence, infection, insomnia, libido decreased, male genital disorder, nausea, nervousness, somnolence, sweating, tremor, yawn. (6) To report SUSPECTED ADVERSE REACTIONS, contact Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data for paroxetine are from: 6-week clinical trials in MDD patients who received paroxetine 20 mg to 50 mg once daily 12-week clinical trials in OCD patients who received paroxetine 20 mg to 60 mg once daily 10- to 12-week clinical trials in PD patients who received paroxetine 10 mg to 60 mg once daily 12-week clinical trials in SAD patients who received paroxetine 20 mg to 50 mg once daily 8-week clinical trials in GAD patients who received paroxetine 10 mg to 50 mg once daily 12-week clinical trials in PTSD patients who received paroxetine 20 mg to 50 mg once daily Adverse Reactions Leading to Discontinuation Twenty percent (1,199/6,145) of patients treated with paroxetine in clinical trials in MDD and 16.1% (84/522), 11.8% (64/542), 9.4% (44/469), 10.7% (79/735), and 11.7% (79/676) of patients treated with paroxetine in clinical trials in SAD, OCD, PD, GAD, and PTSD, respectively, discontinued treatment due to an adverse reaction. The most common adverse reactions (≥ 1%) associated with discontinuation (i.e., those adverse reactions associated with dropout at a rate approximately twice or greater for paroxetine compared to placebo) are presented in Table 3. Table 3 Adverse Reactions Reported as Leading to Discontinuation (≥ 1% of Paroxetine-Treated Patients and Greater than Placebo) in MDD, OCD, PD, SAD, GAD, and PTSD Trials Where numbers are not provided the incidence of the adverse reactions in patients treated with paroxetine was not > 1% or was not greater than or equal to 2 times the incidence of placebo.

eading to Discontinuation (≥ 1% of Paroxetine-Treated Patients and Greater than Placebo) in MDD, OCD, PD, SAD, GAD, and PTSD Trials Where numbers are not provided the incidence of the adverse reactions in patients treated with paroxetine was not > 1% or was not greater than or equal to 2 times the incidence of placebo. MDD OCD PD SAD GAD PTSD Paroxetine Placebo Paroxetine Placebo Paroxetine Placebo Paroxetine Placebo Paroxetine Placebo Paroxetine Placebo % % % % % % % % % % % % CNS Somnolence 2.3 0.7 - 1.9 0.3 3.4 0.3 2 0.2 2.8 0.6 Insomnia - - 1.7 0 1.3 0.3 3.1 0 - - Agitation 1.1 0.5 - - - Tremor 1.1 0.3 - 1.7 0 1 0.2 Anxiety - - - 1.1 0 - - Dizziness - - 1.5 0 1.9 0 1 0.2 - - Gastrointestinal Constipation - 1.1 0 - - Nausea 3.2 1.1 1.9 0 3.2 1.2 4 0.3 2 0.2 2.2 0.6 Diarrhea 1 0.3 - Dry Mouth 1 0.3 - - - Vomiting 1 0.3 - 1 0 - - Flatulence 1 0.3 - - Other Asthenia 1.6 0.4 1.9 0.4 2.5 0.6 1.8 0.2 1.6 0.2 Abnormal Ejaculation Incidence corrected for gender. 1.6 0 2.1 0 4.9 0.6 2.5 0.5 - - Sweating 1 0.3 - 1.1 0 1.1 0.2 - - Impotence - 1.5 0 - - Libido Decreased 1 0 - - Most Common Adverse Reactions The most commonly observed adverse reactions associated with the use of paroxetine (incidence of 5% or greater and at least twice that for placebo) were: MDD: Asthenia, sweating, nausea, decreased appetite, somnolence, dizziness, insomnia, tremor, nervousness, ejaculatory disturbance, and other male genital disorders. OCD: Nausea, dry mouth, decreased appetite, constipation, dizziness, somnolence, tremor, sweating, impotence, and abnormal ejaculation. PD: Asthenia, sweating, decreased appetite, libido decreased, tremor, abnormal ejaculation, female genital disorders, and impotence. SAD: Sweating, nausea, dry mouth, constipation, decreased appetite, somnolence, tremor, libido decreased, yawn, abnormal ejaculation, female genital disorders, and impotence. GAD: Asthenia, infection, constipation, decreased appetite, dry mouth, nausea, libido decreased, somnolence, tremor, sweating, and abnormal ejaculation. PTSD: Asthenia, sweating, nausea, dry mouth, diarrhea, decreased appetite, somnolence, libido decreased, abnormal ejaculation, female genital disorders, and impotence. Adverse Reactions in Patients with MDD Table 4 presents the adverse reactions that occurred at an incidence of 1% or more and greater than placebo in clinical trials of paroxetine-treated patients with MDD. Table 4 Adverse Reactions (≥ l% of Paroxetine-Treated Patients and Greater than Placebo) in 6-Week Clinical Trials for MDD Body System/Adverse Reaction Paroxetine (n = 421) % Placebo (n = 421) % Body as a Whole Headache 18 17 Asthenia 15 6 Cardiovascular Palpitation 3 1 Vasodilation 3 1 Dermatologic Sweating 11 2 Rash 2 1 Gastrointestinal Nausea 26 9 Dry Mouth 18 12 Constipation 14 9 Diarrhea 12 8 Decreased Appetite 6 2 Flatulence 4 2 Oropharynx Disorder Includes mostly "lump in throat" and "tightness in throat." 2 0 Dyspepsia 2 1 Musculoskeletal Myopathy 2 1 Myalgia 2 1 Myasthenia 1 0 Nervous System Somnolence 23 9 Dizziness 13 6 Insomnia 13 6 Tremor 8 2 Nervousness 5 3 Anxiety 5 3 Paresthesia 4 2 Libido Decreased 3 0 Drugged Feeling 2 1 Confusion 1 0 Respiration Yawn 4 0 Special Senses Blurred Vision 4 1 Taste Perversion 2 0 Urogenital System Ejaculatory Disturbance Percentage corrected for gender.

Nervous System Somnolence 23 9 Dizziness 13 6 Insomnia 13 6 Tremor 8 2 Nervousness 5 3 Anxiety 5 3 Paresthesia 4 2 Libido Decreased 3 0 Drugged Feeling 2 1 Confusion 1 0 Respiration Yawn 4 0 Special Senses Blurred Vision 4 1 Taste Perversion 2 0 Urogenital System Ejaculatory Disturbance Percentage corrected for gender. , Mostly "ejaculatory delay." 13 0 Other Male Genital Disorders , Includes "anorgasmia," "erectile difficulties," "delayed ejaculation/orgasm," and "sexual dysfunction," and "impotence." 10 0 Urinary Frequency 3 1 Urinary Disorder Includes mostly "difficulty with micturition" and "urinary hesitancy." 3 0 Female Genital Disorders , Includes mostly "anorgasmia" and "difficulty reaching climax/orgasm." 2 0 Adverse Reactions in Patients with OCD, PD, and SAD Table 5 presents adverse reactions that occurred at a frequency of 2% or more in clinical trials in patients with OCD, PD, and SAD. Table 5 Adverse Reactions (≥ 2% of Paroxetine-Treated Patients and Greater than Placebo) in 10 to 12-Week Clinical Trials for OCD, PD, and SAD Body System/Preferred Term Obsessive Compulsive Disorder Panic Disorder Social Anxiety Disorder Paroxetine Placebo Paroxetine Placebo Paroxetine Placebo (n = 542) (n = 265) (n = 469) (n = 324) (n = 425) (n = 339) % % % % % % Body as a Whole Asthenia 22 14 14 5 22 14 Abdominal Pain - - 4 3 - - Chest Pain 3 2 - - - - Back Pain - - 3 2 - - Chills 2 1 2 1 - - Trauma - - - - 3 1 Cardiovascular Vasodilation 4 1 - - - - Palpitation 2 0 - - - - Dermatologic Sweating 9 3 14 6 9 2 Rash 3 2 - - - - Gastrointestinal Nausea 23 10 23 17 25 7 Dry Mouth 18 9 18 11 9 3 Constipation 16 6 8 5 5 2 Diarrhea 10 10 12 7 9 6 Decreased Appetite 9 3 7 3 8 2 Dyspepsia - - - - 4 2 Flatulence - - - - 4 2 Increased Appetite 4 3 2 1 - - Vomiting - - - - 2 1 Musculoskeletal Myalgia - - - - 4 3 Nervous System Insomnia 24 13 18 10 21 16 Somnolence 24 7 19 11 22 5 Dizziness 12 6 14 10 11 7 Tremor 11 1 9 1 9 1 Nervousness 9 8 - - 8 7 Libido Decreased 7 4 9 1 12 1 Agitation - - 5 4 3 1 Anxiety - - 5 4 5 4 Abnormal Dreams 4 1 - - - - Concentration Impaired 3 2 - - 4 1 Depersonalization 3 0 - - - - Myoclonus 3 0 3 2 2 1 Amnesia 2 1 - - - - Respiratory System Rhinitis - - 3 0 - - Pharyngitis - - - - 4 2 Yawn - - - - 5 1 Special Senses Abnormal Vision 4 2 - - 4 1 Taste Perversion 2 0 - - - - Urogenital System Abnormal Ejaculation Percentage corrected for gender. 23 1 21 1 28 1 Dysmenorrhea - - - - 5 4 Female Genital Disorders 3 0 9 1 9 1 Impotence 8 1 5 0 5 1 Urinary Frequency 3 1 2 0 - - Urination Impaired 3 0 - - - - Urinary Tract Infection 2 1 2 1 - - Adverse Reactions in Patients with GAD and PTSD Table 6 presents adverse reactions that occurred at a frequency of 2% or more in clinical trials in patients with GAD and PTSD. Table 6 Adverse Reactions (≥ 2% of Paroxetine-Treated Patients and Greater than Placebo) in 8- to 12-Week Clinical Trials for GAD and PTSD Percentage corrected for gender.

ts with GAD and PTSD Table 6 presents adverse reactions that occurred at a frequency of 2% or more in clinical trials in patients with GAD and PTSD. Table 6 Adverse Reactions (≥ 2% of Paroxetine-Treated Patients and Greater than Placebo) in 8- to 12-Week Clinical Trials for GAD and PTSD Percentage corrected for gender. Body System/Preferred Term Generalized Anxiety Disorder Posttraumatic Stress Disorder Paroxetine Placebo Paroxetine Placebo (n = 735) (n = 529) (n = 676) (n = 504) % % % % Body as a Whole Asthenia 14 6 12 4 Headache 17 14 - - Infection 6 3 5 4 Abdominal Pain 4 3 Trauma 6 5 Cardiovascular Vasodilation 3 1 2 1 Dermatologic Sweating 6 2 5 1 Gastrointestinal Nausea 20 5 19 8 Dry Mouth 11 5 10 5 Constipation 10 2 5 3 Diarrhea 9 7 11 5 Decreased Appetite 5 1 6 3 Vomiting 3 2 3 2 Dyspepsia - - 5 3 Nervous System Insomnia 11 8 12 11 Somnolence 15 5 16 5 Dizziness 6 5 6 5 Tremor 5 1 4 1 Nervousness 4 3 - - Libido Decreased 9 2 5 2 Abnormal Dreams 3 Respiratory System Respiratory Disorder 7 5 - - Sinusitis 4 3 - - Yawn 4 - 2 < 1 Special Senses Abnormal Vision 2 1 3 1 Urogenital System Abnormal Ejaculation 25 2 13 2 Female Genital Disorder 4 1 5 1 Impotence 4 3 9 1 Dose Dependent Adverse Reactions MDD A comparison of adverse reaction rates in a fixed-dose study comparing paroxetine 10 mg, 20 mg, 30 mg, and 40 mg once daily with placebo in the treatment of MDD revealed dose dependent adverse reactions, as shown in Table 7. Table 7 Adverse Reactions (≥ 5% of Paroxetine-Treated Patients and ≥ Twice the Rate of Placebo) (in a Dose-Comparison Trial in the Treatment of MDD) Body System/Preferred Term Placebo Paroxetine n=51 10 mg n=102 20 mg n=104 30 mg n=101 40 mg n=102 % % % % % Body as a Whole Asthenia 0 2.9 10.6 13.9 12.7 Dermatology Sweating 2 1 6.7 8.9 11.8 Gastrointestinal Constipation 5.9 4.9 7.7 9.9 12.7 Decreased Appetite 2 2 5.8 4 4.9 Diarrhea 7.8 9.8 19.2 7.9 14.7 Dry Mouth 2 10.8 18.3 15.8 20.6 Nausea 13.7 14.7 26.9 34.7 36.3 Nervous System Anxiety 0 2 5.8 5.9 5.9 Dizziness 3.9 6.9 6.7 8.9 12.7 Nervousness 0 5.9 5.8 4 2.9 Paresthesia 0 2.9 1 5 5.9 Somnolence 7.8 12.7 18.3 20.8 21.6 Tremor 0 0 7.7 7.9 14.7 Special Senses Blurred Vision 2 2.9 2.9 2 7.8 Urogenital System Abnormal Ejaculation 0 5.8 6.5 10.6 13 Impotence 0 1.9 4.3 6.4 1.9 Male Genital Disorders 0 3.8 8.7 6.4 3.7 OCD In a fixed-dose study comparing placebo and paroxetine 20 mg, 40 mg, and 60 mg in the treatment of OCD, there was no clear relationship between adverse reactions and the dose of paroxetine to which patients were assigned. PD In a fixed-dose study comparing placebo and paroxetine 10 mg, 20 mg, and 40 mg in the treatment of PD, the following adverse reactions were shown to be dose-dependent: asthenia, dry mouth, anxiety, libido decreased, tremor, and abnormal ejaculation. SAD In a fixed-dose study comparing placebo and paroxetine 20 mg, 40 mg and 60 mg in the treatment of SAD, for most of the adverse reactions, there was no clear relationship between adverse reactions and the dose of paroxetine to which patients were assigned. GAD In a fixed-dose study comparing placebo and paroxetine 20 mg and 40 mg in the treatment of GAD, the following adverse reactions were shown to be dose-dependent: asthenia, constipation, and abnormal ejaculation. PTSD In a fixed-dose study comparing placebo and paroxetine 20 mg and 40 mg in the treatment of PTSD, the following adverse reactions were shown to be dose-dependent: impotence and abnormal ejaculation. Male and Female Sexual Dysfunction Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of SSRI treatment.

he following adverse reactions were shown to be dose-dependent: impotence and abnormal ejaculation. Male and Female Sexual Dysfunction Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of SSRI treatment. However, reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, however, in part because patients and healthcare providers may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in labeling may underestimate their actual incidence. The percentage of patients reporting symptoms of sexual dysfunction in males and females with MDD, OCD, PD, SAD, GAD, and PTSD are displayed in Table 8. Table 8 Adverse Reactions Related to Sexual Dysfunction in Patients Treated with Paroxetine in Clinical Trials of MDD, OCD, PD, SAD, GAD, and PTSD Paroxetine Placebo n (males) 1,446 1,042 % % Decreased Libido 6 to15 0 to 5 Ejaculatory Disturbance 13 to 28 0 to 2 Impotence 2 to 9 0 to 3 n (females) 1,822 1,340 % % Decreased Libido 0 to 9 0 to 2 Orgasmic Disturbance 2 to 9 0 to 1 Paroxetine treatment has been associated with several cases of priapism. In those cases with a known outcome, patients recovered without sequelae. Hallucinations In pooled clinical trials of paroxetine, hallucinations were observed in 0.2% of paroxetine-treated patients compared to 0.1% of patients receiving placebo. Less Common Adverse Reactions The following adverse reactions occurred during the clinical studies of paroxetine and are not included elsewhere in the labeling. Adverse reactions are categorized by body system and listed in order of decreasing frequency according to the following definitions: Frequent adverse reactions are those occurring on 1 or more occasions in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1,000 patients; rare adverse reactions are those occurring in fewer than 1/1,000 patients. Body as a Whole Infrequent: Allergic reaction, chills, face edema, malaise, neck pain; rare: Adrenergic syndrome, cellulitis, moniliasis, neck rigidity, pelvic pain, peritonitis, sepsis, ulcer. Cardiovascular System Frequent: Hypertension, tachycardia; infrequent: Bradycardia, hematoma, hypotension, migraine, postural hypotension, syncope; rare: Angina pectoris, arrhythmia nodal, atrial fibrillation, bundle branch block, cerebral ischemia, cerebrovascular accident, congestive heart failure, heart block, low cardiac output, myocardial infarct, myocardial ischemia, pallor, phlebitis, pulmonary embolus, supraventricular extrasystoles, thrombophlebitis, thrombosis, varicose vein, vascular headache, ventricular extrasystoles. Digestive System Infrequent: Bruxism, colitis, dysphagia, eructation, gastritis, gastroenteritis, gingivitis, glossitis, increased salivation, abnormal liver function tests, rectal hemorrhage, ulcerative stomatitis; rare: Aphthous stomatitis, bloody diarrhea, bulimia, cardiospasm, cholelithiasis, duodenitis, enteritis, esophagitis, fecal impactions, fecal incontinence, gum hemorrhage, hematemesis, hepatitis, ileitis, ileus, intestinal obstruction, jaundice, melena, mouth ulceration, peptic ulcer, salivary gland enlargement, sialadenitis, stomach ulcer, stomatitis, tongue discoloration, tongue edema, tooth caries. Endocrine System Rare: Diabetes mellitus, goiter, hyperthyroidism, hypothyroidism, thyroiditis.

sis, hepatitis, ileitis, ileus, intestinal obstruction, jaundice, melena, mouth ulceration, peptic ulcer, salivary gland enlargement, sialadenitis, stomach ulcer, stomatitis, tongue discoloration, tongue edema, tooth caries. Endocrine System Rare: Diabetes mellitus, goiter, hyperthyroidism, hypothyroidism, thyroiditis. Hemic and Lymphatic Systems Infrequent: Anemia, leukopenia, lymphadenopathy, purpura; rare: Abnormal erythrocytes, basophilia, bleeding time increased, eosinophilia, hypochromic anemia, iron deficiency anemia, leukocytosis, lymphedema, abnormal lymphocytes, lymphocytosis, microcytic anemia, monocytosis, normocytic anemia, thrombocythemia, thrombocytopenia. Metabolic and Nutritional Frequent: Weight gain; infrequent: Edema, peripheral edema, SGOT increased, SGPT increased, thirst, weight loss; rare: Alkaline phosphatase increased, bilirubinemia, BUN increased, creatinine phosphokinase increased, dehydration, gamma globulins increased, gout, hypercalcemia, hypercholesteremia, hyperglycemia, hyperkalemia, hyperphosphatemia, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, ketosis, lactic dehydrogenase increased, non-protein nitrogen (NPN) increased. Musculoskeletal System Frequent: Arthralgia; infrequent: Arthritis, arthrosis; rare: Bursitis, myositis, osteoporosis, generalized spasm, tenosynovitis, tetany. Nervous System Frequent: Emotional lability, vertigo; infrequent: Abnormal thinking, alcohol abuse, ataxia, dystonia, dyskinesia, euphoria, hostility, hypertonia, hypesthesia, hypokinesia, incoordination, lack of emotion, libido increased, manic reaction, neurosis, paralysis, paranoid reaction; rare: Abnormal gait, akinesia, antisocial reaction, aphasia, choreoathetosis, circumoral paresthesias, convulsion, delirium, delusions, diplopia, drug dependence, dysarthria, extrapyramidal syndrome, fasciculations, grand mal convulsion, hyperalgesia, hysteria, manic-depressive reaction, meningitis, myelitis, neuralgia, neuropathy, nystagmus, peripheral neuritis, psychotic depression, psychosis, reflexes decreased, reflexes increased, stupor, torticollis, trismus, withdrawal syndrome. Respiratory System Infrequent: Asthma, bronchitis, dyspnea, epistaxis, hyperventilation, pneumonia, respiratory flu; rare: Emphysema, hemoptysis, hiccups, lung fibrosis, pulmonary edema, sputum increased, stridor, voice alteration. Skin and Appendages Frequent: Pruritus; infrequent: Acne, alopecia, contact dermatitis, dry skin, ecchymosis, eczema, herpes simplex, photosensitivity, urticaria; rare: Angioedema, erythema nodosum, erythema multiforme, exfoliative dermatitis, fungal dermatitis, furunculosis; herpes zoster, hirsutism, maculopapular rash, seborrhea, skin discoloration, skin hypertrophy, skin ulcer, sweating decreased, vesiculobullous rash. Special Senses Frequent: Tinnitus; infrequent: Abnormality of accommodation, conjunctivitis, ear pain, eye pain, keratoconjunctivitis, mydriasis, otitis media; rare: Amblyopia, anisocoria, blepharitis, cataract, conjunctival edema, corneal ulcer, deafness, exophthalmos, eye hemorrhage, glaucoma, hyperacusis, night blindness, otitis externa, parosmia, photophobia, ptosis, retinal hemorrhage, taste loss, visual field defect. Urogenital System Infrequent: Amenorrhea, breast pain, cystitis, dysuria, hematuria, menorrhagia, nocturia, polyuria, pyuria, urinary incontinence, urinary retention, urinary urgency, vaginitis; rare: Abortion, breast atrophy, breast enlargement, endometrial disorder, epididymitis, female lactation, fibrocystic breast, kidney calculus, kidney pain, leukorrhea, mastitis, metrorrhagia, nephritis, oliguria, salpingitis, urethritis, urinary casts, uterine spasm, urolith, vaginal hemorrhage, vaginal moniliasis.

is; rare: Abortion, breast atrophy, breast enlargement, endometrial disorder, epididymitis, female lactation, fibrocystic breast, kidney calculus, kidney pain, leukorrhea, mastitis, metrorrhagia, nephritis, oliguria, salpingitis, urethritis, urinary casts, uterine spasm, urolith, vaginal hemorrhage, vaginal moniliasis. 6.2 Postmarketing Experience The following reactions have been identified during post approval use of paroxetine. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Acute pancreatitis, elevated liver function tests (the most severe cases were deaths due to liver necrosis, and grossly elevated transaminases associated with severe liver dysfunction), Guillain-Barré syndrome, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), syndrome of inappropriate ADH secretion, prolactinemia and galactorrhea; extrapyramidal symptoms which have included akathisia, bradykinesia, cogwheel rigidity, oculogyric crisis which has been associated with concomitant use of pimozide; status epilepticus, acute renal failure, pulmonary hypertension, allergic alveolitis, anosmia, hyposmia, anaphylaxis, eclampsia, laryngismus, optic neuritis, porphyria, restless legs syndrome (RLS), ventricular fibrillation, ventricular tachycardia (including torsade de pointes), hemolytic anemia, events related to impaired hematopoiesis (including aplastic anemia, pancytopenia, bone marrow aplasia, and agranulocytosis), vasculitic syndromes (such as Henoch-Schönlein purpura), and premature births in pregnant women. There has been a case report of severe hypotension when paroxetine was added to chronic metoprolol treatment.

<table width="100%" ID="_RefID655"><caption>Table 3 Adverse Reactions Reported as Leading to Discontinuation (&#x2265; 1% of Paroxetine-Treated Patients and Greater than Placebo) in MDD, OCD, PD, SAD, GAD, and PTSD Trials</caption><colgroup><col width="11%"/><col width="8%"/><col width="7%"/><col width="8%"/><col width="7%"/><col width="8%"/><col width="7%"/><col width="8%"/><col width="7%"/><col width="8%"/><col width="7%"/><col width="8%"/><col width="7%"/></colgroup><tfoot><tr><td align="left" colspan="13" valign="top">Where numbers are not provided the incidence of the adverse reactions in patients treated with paroxetine was not &gt; 1% or was not greater than or equal to 2 times the incidence of placebo.</td></tr></tfoot><tbody><tr><td styleCode="Rrule Lrule Toprule " valign="middle"/><td align="center" colspan="2" styleCode="Rrule Botrule Toprule " valign="middle"><paragraph><content styleCode="bold">MDD</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Toprule " valign="middle"><paragraph><content styleCode="bold">OCD</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Toprule " valign="middle"><paragraph><content styleCode="bold">PD</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Toprule " valign="middle"><paragraph><content styleCode="bold">SAD</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Toprule " valign="middle"><paragraph><content styleCode="bold">GAD</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Toprule " valign="middle"><paragraph><content styleCode="bold">PTSD</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"/><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">Paroxetine</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">Placebo</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">Paroxetine</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">Placebo</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">Paroxetine</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">Placebo</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">Paroxetine</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">Placebo</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">Paroxetine</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">Placebo</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">Paroxetine</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">Placebo</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"/><td align="center" styleCode="Rrule Botrule " valign="middle"><p

ntent styleCode="bold">Paroxetine</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">Placebo</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"/><td align="center" styleCode="Rrule Botrule " valign="middle"><p aragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">CNS</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Somnolence</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2.3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0.7</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td styleCode="Rrule " valign="middle"/><td align="center" styleCode="Rrule " valign="middle"><paragraph>1.9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0.3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3.4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0.3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0.2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2.8</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0.6</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Insomnia</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1.7</paragraph></td><td align="center" styleCode="Rru

paragraph> Insomnia</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1.7</paragraph></td><td align="center" styleCode="Rru le " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1.3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0.3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3.1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Agitation</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1.1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0.5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Tremor</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1.1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0.3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td align="center" styleCode="Rrule " valign="middle"><paragraph>1.7</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0.2</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Anxiety</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td align="center" styleCode="Rrule " valign="middle"><paragraph>1.1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Dizziness</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrul

><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Dizziness</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrul e " valign="middle"><paragraph>1.5</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0</paragraph></td><td styleCode="Rrule Botrule " valign="middle"/><td styleCode="Rrule Botrule " valign="middle"/><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1.9</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0.2</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Gastrointestinal</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Constipation</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td styleCode="Rrule " valign="middle"/><td align="center" styleCode="Rrule " valign="middle"><paragraph>1.1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Nausea</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3.2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1.1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1.9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3.2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1.2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0.3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0.2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2.2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0.6</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Diarrhea</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode=

><paragraph>2.2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0.6</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Diarrhea</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode= "Rrule " valign="middle"><paragraph>0.3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Dry Mouth</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0.3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Vomiting</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0.3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Flatulence</paragraph></td><td styleCode="Rrule Botrule " valign="middle"/><td styleCode="Rrule Botrule " valign="middle"/><td styleCode="Rrule Botrule " valign="middle"/><td styleCode="Rrule Botrule " valign="middle"/><td styleCode="Rrule Botrule " valign="middle"/><td styleCode="Rrule Botrule " valign="middle"/><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0.3</paragraph></td><td styleCode="Rrule Botrule " valign="middle"/><td styleCode="Rrule Botrule " valign="middle"/><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Other</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td

styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Asthenia</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1.6</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0.4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1.9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0.4</paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td align="center" styleCode="Rrule " valign="middle"><paragraph>2.5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0.6</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1.8</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0.2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1.6</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0.2</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Abnormal Ejaculation <footnote ID="_Ref90305258">Incidence corrected for gender.</footnote></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1.6</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2.1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td align="center" styleCode="Rrule " valign="middle"><paragraph>4.9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0.6</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2.5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0.5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Sweating</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0.3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td align="center" styleCode="Rrule " valign="middle"><paragraph>1.1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1.1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0.2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Impotence <footnoteRef IDREF="_Ref90305258"/></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td styleCode="Rrule " valign="middle"/><td align="center" styleCode="Rrule " valign="midd

>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Impotence <footnoteRef IDREF="_Ref90305258"/></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td styleCode="Rrule " valign="middle"/><td align="center" styleCode="Rrule " valign="midd le"><paragraph>1.5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="middle"><paragraph> Libido Decreased</paragraph></td><td styleCode="Rrule Botrule " valign="middle"/><td styleCode="Rrule Botrule " valign="middle"/><td styleCode="Rrule Botrule " valign="middle"/><td styleCode="Rrule Botrule " valign="middle"/><td styleCode="Rrule Botrule " valign="middle"/><td styleCode="Rrule Botrule " valign="middle"/><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0</paragraph></td><td styleCode="Rrule Botrule " valign="middle"/><td styleCode="Rrule Botrule " valign="middle"/><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td></tr></tbody></table>

ph>0</paragraph></td><td styleCode="Rrule Botrule " valign="middle"/><td styleCode="Rrule Botrule " valign="middle"/><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td></tr></tbody></table> <table width="100%" ID="_RefID657"><caption>Table 4 Adverse Reactions (&#x2265; l% of Paroxetine-Treated Patients and Greater than Placebo) in 6-Week Clinical Trials for MDD</caption><colgroup><col width="35%"/><col width="33%"/><col width="32%"/></colgroup><tbody><tr><td styleCode="Rrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">Body System/Adverse Reaction</content></paragraph></td><td align="center" styleCode="Rrule Toprule " valign="middle"><paragraph><content styleCode="bold">Paroxetine</content></paragraph><paragraph><content styleCode="bold">(n = 421)</content></paragraph><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Toprule " valign="middle"><paragraph><content styleCode="bold">Placebo</content></paragraph><paragraph><content styleCode="bold">(n = 421)</content></paragraph><paragraph><content styleCode="bold">%</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Body as a Whole</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Headache</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>18</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>17</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Asthenia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>15</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>6</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Cardiovascular</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Palpitation</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Vasodilation</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Dermatologic</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Sweating</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>11</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Rash</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Gastrointestinal</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Nausea</paragraph></td><t

paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Gastrointestinal</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Nausea</paragraph></td><t d align="center" styleCode="Rrule " valign="middle"><paragraph>26</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>9</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Dry Mouth</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>18</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>12</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Constipation</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>9</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Diarrhea</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>12</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>8</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Decreased Appetite</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>6</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Flatulence</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Oropharynx Disorder <footnote ID="_Ref90313104">Includes mostly &quot;lump in throat&quot; and &quot;tightness in throat.&quot;</footnote></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Dyspepsia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Musculoskeletal</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Myopathy</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Myalgia</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Myasthenia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Nervous System</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Somnolence</paragraph></td><td align="center" styleCode="Rrule " valign="

rule " valign="middle"><paragraph><content styleCode="bold">Nervous System</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Somnolence</paragraph></td><td align="center" styleCode="Rrule " valign=" middle"><paragraph>23</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>9</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Dizziness</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>13</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>6</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Insomnia</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>13</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>6</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Tremor</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>8</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Nervousness</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Anxiety</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Paresthesia</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Libido Decreased</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Drugged Feeling</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Confusion</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Respiration</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Yawn</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Special Senses</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Blurred Vision</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middl

tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Blurred Vision</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middl e"><paragraph> Taste Perversion</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Urogenital System</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Ejaculatory Disturbance <footnote ID="_Ref90306099">Percentage corrected for gender.</footnote>^,<footnote ID="_Ref90306108">Mostly &quot;ejaculatory delay.&quot;</footnote></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>13</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Other Male Genital Disorders <footnoteRef IDREF="_Ref90306099"/>^,<footnote ID="_Ref90313119">Includes &quot;anorgasmia,&quot; &quot;erectile difficulties,&quot; &quot;delayed ejaculation/orgasm,&quot; and &quot;sexual dysfunction,&quot; and &quot;impotence.&quot;</footnote></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>10</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Urinary Frequency</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Urinary Disorder <footnote ID="_Ref90313129">Includes mostly &quot;difficulty with micturition&quot; and &quot;urinary hesitancy.&quot;</footnote></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="middle"><paragraph> Female Genital Disorders <footnoteRef IDREF="_Ref90306099"/>^,<footnote ID="_Ref90313151">Includes mostly &quot;anorgasmia&quot; and &quot;difficulty reaching climax/orgasm.&quot;</footnote></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0</paragraph></td></tr></tbody></table>

Includes mostly &quot;anorgasmia&quot; and &quot;difficulty reaching climax/orgasm.&quot;</footnote></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0</paragraph></td></tr></tbody></table> <table width="100%" ID="_RefID659"><caption>Table 5 Adverse Reactions (&#x2265; 2% of Paroxetine-Treated Patients and Greater than Placebo) in 10 to 12-Week Clinical Trials for OCD, PD, and SAD</caption><colgroup><col width="21%"/><col width="14%"/><col width="12%"/><col width="14%"/><col width="12%"/><col width="14%"/><col width="12%"/></colgroup><tbody><tr><td rowspan="3" styleCode="Rrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">Body System/Preferred Term</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Toprule " valign="middle"><paragraph><content styleCode="bold">Obsessive Compulsive Disorder</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Toprule " valign="middle"><paragraph><content styleCode="bold">Panic Disorder</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Toprule " valign="middle"><paragraph><content styleCode="bold">Social Anxiety Disorder</content></paragraph></td></tr><tr><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">Paroxetine</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">Placebo</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">Paroxetine</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">Placebo</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">Paroxetine</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">Placebo</content></paragraph></td></tr><tr><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">(n = 542)</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">(n = 265)</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">(n = 469)</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">(n = 324)</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">(n = 425)</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">(n = 339)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"/><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Body as a Whole</content>

gn="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Body as a Whole</content> </paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold"> </content>Asthenia </paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>22</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>22</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>14</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Abdominal Pain</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Chest Pain</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Back Pain</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Chills</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Trauma</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"

enter" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Trauma</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle" ><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Cardiovascular</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Vasodilation</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Palpitation</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Dermatologic</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Sweating</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>6</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Rash</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-

e="Rrule Botrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>- </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Gastrointestinal</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Nausea</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>23</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>10</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>23</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>17</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>25</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>7</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Dry Mouth</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>18</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>18</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>11</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Constipation</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>16</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>6</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>8</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Diarrhea</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>10</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>10</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>12</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>7</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>6</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Decreased Appetite</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>7</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>8</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="mi

raph>7</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>8</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="mi ddle"><paragraph> Dyspepsia</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Flatulence</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Increased Appetite</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Vomiting</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Musculoskeletal</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Myalgia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>3</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Nervous System<

e"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>3</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Nervous System< /content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Insomnia</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>24</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>13</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>18</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>10</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>21</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>16</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Somnolence</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>24</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>7</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>19</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>11</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>22</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Dizziness</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>12</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>6</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>10</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>11</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>7</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Tremor</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>11</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Nervousness</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>8</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>8</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>7</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Libido Decreased</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>7</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td a

le " valign="middle"><paragraph>7</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Libido Decreased</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>7</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td a lign="center" styleCode="Rrule " valign="middle"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>12</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Agitation</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Anxiety</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Abnormal Dreams</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Concentration Impaired</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Depersonalization</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Myoclonus</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" sty

n="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Myoclonus</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" sty leCode="Rrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Amnesia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Respiratory System</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Rhinitis</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Pharyngitis</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Yawn</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Special Senses</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode

Botrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Special Senses</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode ="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Abnormal Vision</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Taste Perversion</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Urogenital System</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Abnormal Ejaculation <footnote ID="_Ref90306863">Percentage corrected for gender.</footnote></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>23</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>21</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>28</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Dysmenorrhea</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Female Genital Disorders <footnoteRef IDREF="_Ref90306863"/></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleC

valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleC ode="Rrule " valign="middle"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Impotence <footnoteRef IDREF="_Ref90306863"/></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>8</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Urinary Frequency</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Urination Impaired</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="middle"><paragraph> Urinary Tract Infection</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td></tr></tbody></table>

ragraph>2</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td></tr></tbody></table> <table width="100%" ID="_RefID661"><caption>Table 6 Adverse Reactions (&#x2265; 2% of Paroxetine-Treated Patients and Greater than Placebo) in 8- to 12-Week Clinical Trials for GAD and PTSD <footnote ID="_Ref90307464">Percentage corrected for gender.</footnote></caption><colgroup><col width="26%"/><col width="20%"/><col width="18%"/><col width="20%"/><col width="18%"/></colgroup><tbody><tr><td rowspan="4" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">Body System/Preferred Term</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Toprule " valign="middle"><paragraph><content styleCode="bold">Generalized Anxiety Disorder</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Toprule " valign="middle"><paragraph><content styleCode="bold">Posttraumatic Stress Disorder</content></paragraph></td></tr><tr><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">Paroxetine</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">Placebo</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">Paroxetine</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">Placebo</content></paragraph></td></tr><tr><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">(n = 735)</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">(n = 529)</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">(n = 676)</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">(n = 504)</content></paragraph></td></tr><tr><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Body as a Whole</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Asthenia</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>6</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>12</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Headache</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>17</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</p

><td styleCode="Rrule Lrule " valign="middle"><paragraph> Headache</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>17</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</p aragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Infection</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>6</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Abdominal Pain</paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Trauma</paragraph></td><td styleCode="Rrule Botrule " valign="middle"/><td styleCode="Rrule Botrule " valign="middle"/><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>6</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>5</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Cardiovascular</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Vasodilation</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Dermatologic</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Sweating</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>6</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Gastrointestinal</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Nausea</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>20</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>19</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>8</paragraph></td></tr><tr><td styleCode="Rrule Lr

middle"><paragraph>20</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>19</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>8</paragraph></td></tr><tr><td styleCode="Rrule Lr ule " valign="middle"><paragraph> Dry Mouth</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>11</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>10</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Constipation</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>10</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Diarrhea</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>7</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>11</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Decreased Appetite</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>6</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Vomiting</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Dyspepsia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>3</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Nervous System</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Insomnia</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>11</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>8</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>12</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>11</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Somnolence</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>15</paragraph></td><td align="center" styleCode="Rrule " v

>12</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>11</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Somnolence</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>15</paragraph></td><td align="center" styleCode="Rrule " v align="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>16</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Dizziness</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>6</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>6</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Tremor</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Nervousness</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Libido Decreased</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Abnormal Dreams</paragraph></td><td styleCode="Rrule Botrule " valign="middle"/><td styleCode="Rrule Botrule " valign="middle"/><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>3</paragraph></td><td styleCode="Rrule Botrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Respiratory System</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Respiratory Disorder</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>7</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Sinusitis</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Yawn</paragraph><

tyleCode="Rrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>-</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Yawn</paragraph>< /td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>-</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>&lt; 1</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Special Senses</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Abnormal Vision</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Urogenital System</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Abnormal Ejaculation <footnoteRef IDREF="_Ref90307464"/></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>25</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>13</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Female Genital Disorder <footnoteRef IDREF="_Ref90307464"/></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="middle"><paragraph> Impotence <footnoteRef IDREF="_Ref90307464"/></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1</paragraph></td></tr></tbody></table>

ragraph>4</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>3</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>9</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1</paragraph></td></tr></tbody></table> <table width="100%" ID="_RefID663"><caption>Table 7 Adverse Reactions (&#x2265; 5% of Paroxetine-Treated Patients and &#x2265; Twice the Rate of Placebo) (in a Dose-Comparison Trial in the Treatment of MDD)</caption><colgroup><col width="22%"/><col width="22%"/><col width="14%"/><col width="14%"/><col width="14%"/><col width="14%"/></colgroup><tbody><tr><td rowspan="2" styleCode="Rrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">Body System/Preferred Term</content></paragraph></td><td align="center" styleCode="Rrule Toprule " valign="middle"><paragraph><content styleCode="bold">Placebo</content></paragraph></td><td align="center" colspan="4" styleCode="Rrule Botrule Toprule " valign="middle"><paragraph><content styleCode="bold">Paroxetine</content></paragraph></td></tr><tr><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">n=51</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">10 mg</content> <content styleCode="bold">n=102</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">20 mg</content> <content styleCode="bold">n=104</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">30 mg</content> <content styleCode="bold">n=101</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">40 mg</content> <content styleCode="bold">n=102</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"/><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Body as a Whole</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Asthenia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2.9</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>10.6</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>13.9</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>12.7</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Dermatology</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " v

h></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Dermatology</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " v align="middle"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Sweating</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>6.7</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>8.9</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>11.8</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Gastrointestinal</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Constipation</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5.9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4.9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>7.7</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>9.9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>12.7</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Decreased Appetite</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5.8</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4.9</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Diarrhea</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>7.8</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>9.8</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>19.2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>7.9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>14.7</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Dry Mouth</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>10.8</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>18.3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>15.8</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>20.6</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Nausea</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>13.7</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>14.7</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>26.9</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>34.7</paragraph></td><td align="center" styleCode="Rrule Bo

<td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>14.7</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>26.9</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>34.7</paragraph></td><td align="center" styleCode="Rrule Bo trule " valign="middle"><paragraph>36.3</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Nervous System</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Anxiety</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5.8</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5.9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5.9</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Dizziness</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>3.9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>6.9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>6.7</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>8.9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>12.7</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Nervousness</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5.9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5.8</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2.9</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Paresthesia</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>2.9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5.9</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Somnolence</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>7.8</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>12.7</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>18.3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>20.8</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>21.6</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Tremor</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>7.7</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>7.9</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><parag

ode="Rrule Botrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>7.7</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>7.9</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><parag raph>14.7</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Special Senses</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Blurred Vision</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2.9</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2.9</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>7.8</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">Urogenital System</content></paragraph></td><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/><td styleCode="Rrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Abnormal Ejaculation</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>5.8</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>6.5</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>10.6</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>13</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph> Impotence</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1.9</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>4.3</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>6.4</paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph>1.9</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="middle"><paragraph> Male Genital Disorders</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>3.8</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>8.7</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>6.4</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>3.7</paragraph></td></tr></tbody></table>

3.8</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>8.7</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>6.4</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>3.7</paragraph></td></tr></tbody></table> <table width="100%" ID="_RefID665"><caption>Table 8 Adverse Reactions Related to Sexual Dysfunction in Patients Treated with Paroxetine in Clinical Trials of MDD, OCD, PD, SAD, GAD, and PTSD</caption><colgroup><col width="34%"/><col width="34%"/><col width="33%"/></colgroup><tbody><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="middle"/><td align="center" styleCode="Rrule Botrule Toprule " valign="middle"><paragraph><content styleCode="bold">Paroxetine</content></paragraph></td><td align="center" styleCode="Rrule Botrule Toprule " valign="middle"><paragraph><content styleCode="bold">Placebo</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">n (males)</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">1,446</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">1,042</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"/><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Decreased Libido</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>6 to15</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0 to 5</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Ejaculatory Disturbance</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>13 to 28</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0 to 2</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Impotence</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2 to 9</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0 to 3</paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"><paragraph><content styleCode="bold">n (females)</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">1,822</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">1,340</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"/><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Decreased Libido</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0 to 9</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0 to 2</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="middle"><paragraph> Orgasmic Disturbance</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2 to 9</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0 to 1<

paragraph>0 to 2</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="middle"><paragraph> Orgasmic Disturbance</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2 to 9</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>0 to 1< /paragraph></td></tr></tbody></table>

7 DRUG INTERACTIONS Table 9 presents clinically significant drug interactions with paroxetine. Table 9 Clinically Significant Drug Interactions with Paroxetine Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact The concomitant use of SSRIs, including paroxetine, and MAOIs increases the risk of serotonin syndrome. Intervention Paroxetine is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [see Dosage and Administration (2.5) , Contraindications (4) , Warnings and Precautions (5.2) ]. Examples selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue Pimozide and Thioridazine Clinical Impact Increased plasma concentrations of pimozide and thioridazine, drugs with a narrow therapeutic index, may increase the risk of QTc prolongation and ventricular arrhythmias. Intervention Paroxetine is contraindicated in patients taking pimozide or thioridazine [see Contraindications (4) ]. Other Serotonergic Drugs Clinical Impact The concomitant use of serotonergic drugs with paroxetine increases the risk of serotonin syndrome. Intervention Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of paroxetine and/or concomitant serotonergic drugs [see Warnings and Precautions (5.2) ]. Examples other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, and St. John's Wort Drugs that Interfere with Hemostasis (antiplatelet agents and anticoagulants) Clinical Impact The concurrent use of an antiplatelet agent or anticoagulant with paroxetine may potentiate the risk of bleeding. Intervention Inform patients of the increased risk of bleeding associated with the concomitant use of paroxetine and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio [see Warnings and Precautions (5.5) ]. Examples aspirin, clopidogrel, heparin, warfarin Drugs Highly Bound to Plasma Protein Clinical Impact Paroxetine is highly bound to plasma protein. The concomitant use of paroxetine with another drug that is highly bound to plasma protein may increase free concentrations of paroxetine or other tightly-bound drugs in plasma. Intervention Monitor for adverse reactions and reduce dosage of paroxetine or other protein-bound drugs as warranted. Examples warfarin Drugs Metabolized by CYP2D6 Clinical Impact Paroxetine is a CYP2D6 inhibitor [see Clinical Pharmacology (12.3) ]. The concomitant use of paroxetine with a CYP2D6 substrate may increase the exposure of the CYP2D6 substrate. Intervention Decrease the dosage of a CYP2D6 substrate if needed with concomitant paroxetine use. Conversely, an increase in dosage of a CYP2D6 substrate may be needed if paroxetine is discontinued. Examples propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, venlafaxine, risperidone. Tamoxifen Clinical Impact Concomitant use of tamoxifen with paroxetine may lead to reduced plasma concentrations of the active metabolite (endoxifen) and reduced efficacy of tamoxifen Intervention Consider use of an alternative antidepressant with little or no CYP2D6 inhibition [see Warnings and Precautions (5.11) ].

. Tamoxifen Clinical Impact Concomitant use of tamoxifen with paroxetine may lead to reduced plasma concentrations of the active metabolite (endoxifen) and reduced efficacy of tamoxifen Intervention Consider use of an alternative antidepressant with little or no CYP2D6 inhibition [see Warnings and Precautions (5.11) ]. Fosamprenavir/Ritonavir Clinical Impact Co-administration of fosamprenavir/ritonavir with paroxetine significantly decreased plasma levels of paroxetine. Intervention Any dose adjustment should be guided by clinical effect (tolerability and efficacy). Drugs Highly Bound to Plasma Protein: Monitor for adverse reactions and reduce dosage of paroxetine or other protein-bound drugs (e.g., warfarin) as warranted. (7) Drugs Metabolized by CYP2D6: Reduce dosage of drugs metabolized by CYP2D6 as warranted. (7) Concomitant use with tamoxifen: Consider use of an alternative antidepressant with little or no CYP2D6 inhibition. (5.11 , 7)

<table ID="_RefID747" width="100%"><caption>Table 9 Clinically Significant Drug Interactions with Paroxetine</caption><col width="25%"/><col width="75%"/><tbody><tr><td colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Monoamine Oxidase Inhibitors (MAOIs)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="italics">Clinical Impact</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph>The concomitant use of SSRIs, including paroxetine, and MAOIs increases the risk of serotonin syndrome.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="italics">Intervention</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph>Paroxetine is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue <content styleCode="italics">[see <linkHtml href="#ID599">Dosage and Administration (2.5)</linkHtml>, <linkHtml href="#ID614">Contraindications (4)</linkHtml>, <linkHtml href="#ID624">Warnings and Precautions (5.2)</linkHtml>]. </content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="italics">Examples</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph>selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue</paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Pimozide and Thioridazine</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="italics">Clinical Impact</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph>Increased plasma concentrations of pimozide and thioridazine, drugs with a narrow therapeutic index, may increase the risk of QTc prolongation and ventricular arrhythmias.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="italics">Intervention</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph>Paroxetine is contraindicated in patients taking pimozide or thioridazine <content styleCode="italics">[see <linkHtml href="#ID614">Contraindications (4)</linkHtml>]. </content></paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Other Serotonergic Drugs</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="italics">Clinical Impact</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph>The concomitant use of serotonergic drugs with paroxetine increases the risk of serotonin syndrome.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="italics">Intervention</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph>Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of paroxetine and/or concomitant serotonergic drugs <content styleCode="italics">[see <linkHtml href="#ID624">Warnings and Precautions (5.2)</linkHtml>].

ts for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of paroxetine and/or concomitant serotonergic drugs <content styleCode="italics">[see <linkHtml href="#ID624">Warnings and Precautions (5.2)</linkHtml>]. </content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="italics">Examples</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph>other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, and St. John&apos;s Wort</paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Drugs that Interfere with Hemostasis (antiplatelet agents and anticoagulants)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="italics">Clinical Impact</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph>The concurrent use of an antiplatelet agent or anticoagulant with paroxetine may potentiate the risk of bleeding.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="italics">Intervention</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph>Inform patients of the increased risk of bleeding associated with the concomitant use of paroxetine and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio <content styleCode="italics">[see <linkHtml href="#ID630">Warnings and Precautions (5.5)</linkHtml>]. </content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="italics">Examples</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph>aspirin, clopidogrel, heparin, warfarin</paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Drugs Highly Bound to Plasma Protein</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="italics">Clinical Impact</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph>Paroxetine is highly bound to plasma protein. The concomitant use of paroxetine with another drug that is highly bound to plasma protein may increase free concentrations of paroxetine or other tightly-bound drugs in plasma.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="italics">Intervention</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph>Monitor for adverse reactions and reduce dosage of paroxetine or other protein-bound drugs as warranted.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="italics">Examples</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph>warfarin</paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Drugs Metabolized by CYP2D6</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="italics">Clinical Impact</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph>Paroxetine is a CYP2D6 inhibitor <content styleCode="italics">[see <linkHtml href="#ID702">Clinical Pharmacology (12.3)</linkHtml>]. </content>The concomitant use of paroxetine with a CYP2D6 substrate may increase the exposure of the CYP2D6 substrate.

aragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph>Paroxetine is a CYP2D6 inhibitor <content styleCode="italics">[see <linkHtml href="#ID702">Clinical Pharmacology (12.3)</linkHtml>]. </content>The concomitant use of paroxetine with a CYP2D6 substrate may increase the exposure of the CYP2D6 substrate. </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="italics">Intervention</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph>Decrease the dosage of a CYP2D6 substrate if needed with concomitant paroxetine use. Conversely, an increase in dosage of a CYP2D6 substrate may be needed if paroxetine is discontinued.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="italics">Examples</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph>propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, venlafaxine, risperidone.</paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Tamoxifen</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="italics">Clinical Impact</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph>Concomitant use of tamoxifen with paroxetine may lead to reduced plasma concentrations of the active metabolite (endoxifen) and reduced efficacy of tamoxifen</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="italics">Intervention</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph>Consider use of an alternative antidepressant with little or no CYP2D6 inhibition <content styleCode="italics">[see <linkHtml href="#ID642">Warnings and Precautions (5.11)</linkHtml>]. </content></paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Fosamprenavir/Ritonavir</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="italics">Clinical Impact</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph>Co-administration of fosamprenavir/ritonavir with paroxetine significantly decreased plasma levels of paroxetine.</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="top"><paragraph><content styleCode="italics">Intervention</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph>Any dose adjustment should be guided by clinical effect (tolerability and efficacy).</paragraph></td></tr></tbody></table>

8 USE IN SPECIFIC POPULATIONS Pregnancy: SSRI use, particularly later in pregnancy, may increase the risk for persistent pulmonary hypertension and symptoms of poor adaptation (respiratory distress, temperature instability, feeding difficulty, hypotonia, irritability) in the neonate. (8.1) 8.1 Pregnancy Risk Summary Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions (5.5) and Clinical Considerations]. Paroxetine is associated with a less than 2-fold increase in cardiovascular malformations when administered to a pregnant woman during the first trimester. While individual epidemiological studies on the association between paroxetine use and cardiac malformations have reported inconsistent findings, some meta-analyses of epidemiological studies have identified an increased risk of cardiovascular malformations (see Data) . There are risks of persistent pulmonary hypertension of the newborn (PPHN) (see Data) and/or poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (SSRIs), including paroxetine during pregnancy. There also are risks associated with untreated depression in pregnancy (see Clinical Considerations) . For women who intend to become pregnant or who are in their first trimester of pregnancy, paroxetine should be initiated only after consideration of the other available treatment options. No evidence of treatment related malformations was observed in animal reproduction studies, when paroxetine was administered during the period of organogenesis at doses up to 50 mg/kg/day in rats and 6 mg/kg/day in rabbits. These doses are approximately 8 (rat) and less than 2 (rabbit) times the maximum recommended human dose (MRHD – 60 mg) on an mg/m 2 basis. When paroxetine was administered to female rats during the last trimester of gestation and continued through lactation, there was an increase in the number of pup deaths during the first four days of lactation. This effect occurred at a dose of 1 mg/kg/day which is less than the MRHD on an mg/m 2 basis (See Data) . The background risks of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryofetal risk Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants. This finding is from a prospective, longitudinal study of 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and the postpartum. Maternal Adverse Reactions Use of paroxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions (5.5) ] .

he risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and the postpartum. Maternal Adverse Reactions Use of paroxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions (5.5) ] . Fetal/Neonatal adverse reactions Neonates exposed to paroxetine and other SSRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremors, jitteriness, irritability and constant crying. These findings are consistent with either a direct toxic effect of SSRIs or possibly a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see Warnings and Precautions (5.2) ] . Data Human Data Published epidemiological studies on the association between first trimester paroxetine use and cardiovascular malformations have reported inconsistent results; however, meta-analyses of population-based cohort studies published between 1996 – 2017 indicate a less than 2-fold increased risk for overall cardiovascular malformations. Specific cardiac malformations identified in two meta-analyses include an approximately 2 to 2.5-fold increased risk for right ventricular outflow tract defects. One meta-analysis also identified an increased risk (less than 2-fold) for bulbus cordis anomalies and anomalies of cardiac septal closure, and an increased risk for atrial septal defect (pooled OR 2.38, 95% CI 1.14-4.97). Important limitations of the studies included in these meta-analyses include potential confounding by indication, depression severity and potential exposure misclassification. Exposure to SSRIs, particularly later in pregnancy, may have an increased risk for PPHN. PPHN occurs in 1-2 per 1000 live births in the general population and is associated with substantial neonatal morbidity and mortality. Animal Data Reproduction studies were performed at doses up to 50 mg/kg/day in rats and 6 mg/kg/day in rabbits administered during organogenesis. These doses are approximately 8 (rat) and less than 2 (rabbit) times the maximum recommended human dose (MRHD – 60 mg) on an mg/m2 basis. These studies have revealed no evidence of developmental effects. However, in rats, there was an increase in pup deaths during the first 4 days of lactation when dosing occurred during the last trimester of gestation and continued throughout lactation. This effect occurred at a dose of 1 mg/kg/day which is less than the MRHD on an mg/m2 basis. The no-effect dose for rat pup mortality was not determined. The cause of these deaths is not known. 8.2 Lactation Risk Summary Data from the published literature report the presence of paroxetine in human milk (see Data) . There are reports of agitation, irritability, poor feeding and poor weight gain in infants exposed to paroxetine through breast milk (see Clinical Considerations) . There are no data on the effect of paroxetine on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Paxil and any potential adverse effects on the breastfed child from paroxetine or from underlying maternal condition. Clinical Considerations Infants exposed to paroxetine should be monitored for agitation, irritability, poor feeding and poor weight gain.

g should be considered along with the mother’s clinical need for Paxil and any potential adverse effects on the breastfed child from paroxetine or from underlying maternal condition. Clinical Considerations Infants exposed to paroxetine should be monitored for agitation, irritability, poor feeding and poor weight gain. Data Published literature suggests the presence of paroxetine in human milk with relative infant doses ranging between 0.4% to 2.2%, and a milk/plasma ratio of <1. No significant amounts were detected in the plasma of infants after breastfeeding. 8.3 Females and Males of Reproductive Potential Infertility Male Based on findings from clinical studies, paroxetine may affect sperm quality which may impair fertility; it is not known if this effect is reversible [see Nonclinical Toxicology (13.1) ] . 8.4 Pediatric Use The safety and effectiveness of paroxetine in pediatric patients have not been established [see Box Warning ]. Effectiveness was not demonstrated in three placebo-controlled trials in 752 paroxetine-treated pediatric patients with MDD. Antidepressants increase the risk of suicidal thoughts and behaviors in pediatric patients [see Boxed Warning , Warnings and Precautions (5.1) ]. Decreased appetite and weight loss have been observed in association with the use of SSRIs. In placebo-controlled clinical trials conducted with pediatric patients, the following adverse reactions were reported in at least 2% of pediatric patients treated with paroxetine and occurred at a rate at least twice that for pediatric patients receiving placebo: emotional lability (including self-harm, suicidal thoughts, attempted suicide, crying, and mood fluctuations), hostility, decreased appetite, tremor, sweating, hyperkinesia, and agitation. Adverse reactions upon discontinuation of treatment with paroxetine in the pediatric clinical trials that included a taper phase regimen, which occurred in at least 2% of patients and at a rate at least twice that of placebo, were: emotional lability (including suicidal ideation, suicide attempt, mood changes, and tearfulness), nervousness, dizziness, nausea, and abdominal pain. 8.5 Geriatric Use In premarketing clinical trials with paroxetine, 17% of patients treated with paroxetine (approximately 700) were 65 years of age or older. Pharmacokinetic studies revealed a decreased clearance in the elderly, and a lower starting dose is recommended; however, no overall differences in safety or effectiveness were observed between elderly and younger patients [see Dosage and Administration (2.4) , Clinical Pharmacology (12.3) ]. SSRIs including paroxetine, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [see Warnings and Precautions (5.7) ]. 8.6 Renal and Hepatic Impairment Increased plasma concentrations of paroxetine occur in patients with renal and hepatic impairment. The initial dosage of paroxetine should be reduced in patients with severe renal impairment and in patients with severe hepatic impairment [see Dosage and Administration (2.4) , Clinical Pharmacology (12.3) ].

8.1 Pregnancy Risk Summary Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions (5.5) and Clinical Considerations]. Paroxetine is associated with a less than 2-fold increase in cardiovascular malformations when administered to a pregnant woman during the first trimester. While individual epidemiological studies on the association between paroxetine use and cardiac malformations have reported inconsistent findings, some meta-analyses of epidemiological studies have identified an increased risk of cardiovascular malformations (see Data) . There are risks of persistent pulmonary hypertension of the newborn (PPHN) (see Data) and/or poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (SSRIs), including paroxetine during pregnancy. There also are risks associated with untreated depression in pregnancy (see Clinical Considerations) . For women who intend to become pregnant or who are in their first trimester of pregnancy, paroxetine should be initiated only after consideration of the other available treatment options. No evidence of treatment related malformations was observed in animal reproduction studies, when paroxetine was administered during the period of organogenesis at doses up to 50 mg/kg/day in rats and 6 mg/kg/day in rabbits. These doses are approximately 8 (rat) and less than 2 (rabbit) times the maximum recommended human dose (MRHD – 60 mg) on an mg/m 2 basis. When paroxetine was administered to female rats during the last trimester of gestation and continued through lactation, there was an increase in the number of pup deaths during the first four days of lactation. This effect occurred at a dose of 1 mg/kg/day which is less than the MRHD on an mg/m 2 basis (See Data) . The background risks of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryofetal risk Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants. This finding is from a prospective, longitudinal study of 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and the postpartum. Maternal Adverse Reactions Use of paroxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions (5.5) ] . Fetal/Neonatal adverse reactions Neonates exposed to paroxetine and other SSRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support and tube feeding. Such complications can arise immediately upon delivery.

m hemorrhage [see Warnings and Precautions (5.5) ] . Fetal/Neonatal adverse reactions Neonates exposed to paroxetine and other SSRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremors, jitteriness, irritability and constant crying. These findings are consistent with either a direct toxic effect of SSRIs or possibly a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see Warnings and Precautions (5.2) ] . Data Human Data Published epidemiological studies on the association between first trimester paroxetine use and cardiovascular malformations have reported inconsistent results; however, meta-analyses of population-based cohort studies published between 1996 – 2017 indicate a less than 2-fold increased risk for overall cardiovascular malformations. Specific cardiac malformations identified in two meta-analyses include an approximately 2 to 2.5-fold increased risk for right ventricular outflow tract defects. One meta-analysis also identified an increased risk (less than 2-fold) for bulbus cordis anomalies and anomalies of cardiac septal closure, and an increased risk for atrial septal defect (pooled OR 2.38, 95% CI 1.14-4.97). Important limitations of the studies included in these meta-analyses include potential confounding by indication, depression severity and potential exposure misclassification. Exposure to SSRIs, particularly later in pregnancy, may have an increased risk for PPHN. PPHN occurs in 1-2 per 1000 live births in the general population and is associated with substantial neonatal morbidity and mortality. Animal Data Reproduction studies were performed at doses up to 50 mg/kg/day in rats and 6 mg/kg/day in rabbits administered during organogenesis. These doses are approximately 8 (rat) and less than 2 (rabbit) times the maximum recommended human dose (MRHD – 60 mg) on an mg/m2 basis. These studies have revealed no evidence of developmental effects. However, in rats, there was an increase in pup deaths during the first 4 days of lactation when dosing occurred during the last trimester of gestation and continued throughout lactation. This effect occurred at a dose of 1 mg/kg/day which is less than the MRHD on an mg/m2 basis. The no-effect dose for rat pup mortality was not determined. The cause of these deaths is not known.

8.4 Pediatric Use The safety and effectiveness of paroxetine in pediatric patients have not been established [see Box Warning ]. Effectiveness was not demonstrated in three placebo-controlled trials in 752 paroxetine-treated pediatric patients with MDD. Antidepressants increase the risk of suicidal thoughts and behaviors in pediatric patients [see Boxed Warning , Warnings and Precautions (5.1) ]. Decreased appetite and weight loss have been observed in association with the use of SSRIs. In placebo-controlled clinical trials conducted with pediatric patients, the following adverse reactions were reported in at least 2% of pediatric patients treated with paroxetine and occurred at a rate at least twice that for pediatric patients receiving placebo: emotional lability (including self-harm, suicidal thoughts, attempted suicide, crying, and mood fluctuations), hostility, decreased appetite, tremor, sweating, hyperkinesia, and agitation. Adverse reactions upon discontinuation of treatment with paroxetine in the pediatric clinical trials that included a taper phase regimen, which occurred in at least 2% of patients and at a rate at least twice that of placebo, were: emotional lability (including suicidal ideation, suicide attempt, mood changes, and tearfulness), nervousness, dizziness, nausea, and abdominal pain.

8.5 Geriatric Use In premarketing clinical trials with paroxetine, 17% of patients treated with paroxetine (approximately 700) were 65 years of age or older. Pharmacokinetic studies revealed a decreased clearance in the elderly, and a lower starting dose is recommended; however, no overall differences in safety or effectiveness were observed between elderly and younger patients [see Dosage and Administration (2.4) , Clinical Pharmacology (12.3) ]. SSRIs including paroxetine, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [see Warnings and Precautions (5.7) ].

10 OVERDOSAGE The following have been reported with paroxetine tablet overdosage: Seizures, which may be delayed, and altered mental status including coma. Cardiovascular toxicity, which may be delayed, including QRS and QTc interval prolongation. Hypertension most commonly seen, but rarely can see hypotension alone or with co-ingestants including alcohol. Serotonin syndrome (patients with a multiple drug overdosage with other proserotonergic drugs may have a higher risk). Gastrointestinal decontamination with activated charcoal should be considered in patients who present early after a paroxetine overdose. Consider contacting a Poison Center (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations.

11 DESCRIPTION Paroxetine tablets, USP contains paroxetine hydrochloride, an SSRI. It is the hydrochloride salt of a phenylpiperidine compound identified chemically as (-)- trans -4 R -(4'-fluorophenyl)-3 S -[(3',4'- methylenedioxyphenoxy) methyl] piperidine hydrochloride hemihydrate and has the molecular formula of C 19 H 20 FNO 3 •HCl•1/2H 2 O. The molecular weight is 374.8 (329.4 as free base). The structural formula of paroxetine hydrochloride is: Paroxetine hydrochloride, USP is an odorless, white to off-white crystalline powder, having a melting point range of 120°C to 138°C. It is freely soluble in methanol, soluble in ethanol, sparingly soluble in dichloromethane and slightly soluble in water. Paroxetine tablets are for oral administration. Each film-coated tablet contains 10 mg, 20 mg, 30 mg, or 40 mg of paroxetine equivalent to 11.1 mg, 22.2 mg, 33.3 mg or 44.4 mg of paroxetine hydrochloride, respectively. In addition, each tablet contains the following inactive ingredients: dibasic calcium phosphate anhydrous, hypromellose 6 cP, lactose anhydrous, magnesium stearate, polyethylene glycol 6000, povidone, sodium starch glycolate, talc, and titanium dioxide. Structural Formula

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The mechanism of action of paroxetine in the treatment of MDD, SAD, OCD\, PD, GAD, and PTSD is unknown, but is presumed to be linked to potentiation of serotonergic activity in the central nervous system resulting from inhibition of neuronal reuptake of serotonin (5-hydroxy-tryptamine, 5-HT). 12.2 Pharmacodynamics Studies at clinically relevant doses in humans have demonstrated that paroxetine blocks the uptake of serotonin into human platelets. In vitro studies in animals also suggest that paroxetine is a potent and highly selective inhibitor of neuronal serotonin reuptake (SSRI) and has only very weak effects on norepinephrine and dopamine neuronal reuptake. 12.3 Pharmacokinetics Nonlinearity in pharmacokinetics is observed with increasing doses of paroxetine. In a meta-analysis of paroxetine from 4 studies done in healthy volunteers following multiple dosing of 20 mg/day to 40 mg/day, males did not exhibit a significantly lower C max or AUC than females. Absorption Paroxetine hydrochloride is completely absorbed after oral dosing of a solution of the hydrochloride salt. In a study in which normal male subjects (n = 15) received 30 mg tablets daily for 30 days, steady-state paroxetine concentrations were achieved by approximately 10 days for most subjects, although it may take substantially longer in an occasional patient. At steady state, mean values of C max , T max , C min , and T ½ were 61.7 ng/mL (CV 45%), 5.2 hr. (CV 10%), 30.7 ng/mL (CV 67%), and 21.0 hours (CV 32%), respectively. The steady-state C max and C min values were about 6 and 14 times what would be predicted from single-dose studies. Steady-state drug exposure based on AUC 0-24 was about 8 times greater than would have been predicted from single-dose data in these subjects. The excess accumulation is a consequence of the fact that 1 of the enzymes that metabolizes paroxetine is readily saturable. Paroxetine is equally bioavailable from the oral suspension and tablet. Effect of Food The effects of food on the bioavailability of paroxetine were studied in subjects administered a single dose with and without food. AUC was only slightly increased (6%) when drug was administered with food but the C max was 29% greater, while the time to reach peak plasma concentration decreased from 6.4 hours post-dosing to 4.9 hours. Distribution Paroxetine distributes throughout the body, including the CNS, with only 1% remaining in the plasma. Approximately 95% and 93% of paroxetine is bound to plasma protein at 100 ng/mL and 400 ng/mL, respectively. Under clinical conditions, paroxetine concentrations would normally be less than 400 ng/mL. Paroxetine does not alter the in vitro protein binding of phenytoin or warfarin. Elimination Metabolism The mean elimination half-life is approximately 21 hours (CV 32%) after oral dosing of 30 mg tablets daily for 30 days of paroxetine. In steady-state dose proportionality studies involving elderly and nonelderly patients, at doses of 20 mg to 40 mg daily for the elderly and 20 mg to 50 mg daily for the nonelderly, some nonlinearity was observed in both populations, again reflecting a saturable metabolic pathway. In comparison to C min values after 20 mg daily, values after 40 mg daily were only about 2 to 3 times greater than doubled. Paroxetine is extensively metabolized after oral administration.

0 mg daily for the nonelderly, some nonlinearity was observed in both populations, again reflecting a saturable metabolic pathway. In comparison to C min values after 20 mg daily, values after 40 mg daily were only about 2 to 3 times greater than doubled. Paroxetine is extensively metabolized after oral administration. The principal metabolites are polar and conjugated products of oxidation and methylation, which are readily cleared. Conjugates with glucuronic acid and sulfate predominate, and major metabolites have been isolated and identified. Data indicate that the metabolites have no more than 1/50 the potency of the parent compound at inhibiting serotonin uptake. The metabolism of paroxetine is accomplished in part by CYP2D6. Saturation of this enzyme at clinical doses appears to account for the nonlinearity of paroxetine kinetics with increasing dose and increasing duration of treatment. The role of this enzyme in paroxetine metabolism also suggests potential drug-drug interactions [see Drug Interactions (7) ]. Pharmacokinetic behavior of paroxetine has not been evaluated in subjects who are deficient in CYP2D6 (poor metabolizers). Excretion Approximately 64% of a 30-mg oral solution dose of paroxetine was excreted in the urine with 2% as the parent compound and 62% as metabolites over a 10-day post-dosing period. About 36% was excreted in the feces (probably via the bile), mostly as metabolites and less than 1% as the parent compound over the 10-day post-dosing period. Drug Interaction Studies There are clinically significant, known drug interactions between paroxetine and other drugs [see Drug Interactions (7) ]. Figure 1 Impact of Paroxetine on the Pharmacokinetics of Co-Administered Drugs (log scale) Figure 2 Impact of Co-Administered Drugs on the Pharmacokinetics of Paroxetine Theophylline: Reports of elevated theophylline levels associated with paroxetine treatment have been reported. While this interaction has not been formally studied, it is recommended that theophylline levels be monitored when these drugs are concurrently administered. Drugs Metabolized by Cytochrome CYP3A4 An in vivo interaction study involving the co-administration under steady-state conditions of paroxetine and terfenadine, a substrate for CYP3A4, revealed no effect of paroxetine on terfenadine pharmacokinetics. In addition, in vitro studies have shown ketoconazole, a potent inhibitor of CYP3A4 activity, to be at least 100 times more potent than paroxetine as an inhibitor of the metabolism of several substrates for this enzyme, including terfenadine, triazolam, and cyclosporine. Paroxetine's extent of inhibition of CYP3A4 activity is not expected to be of clinical significance. Specific Populations The impact of specific populations on the pharmacokinetics of paroxetine are shown in Figure 3. The recommended starting dosage and maximum dosage of paroxetine is reduced in elderly patients, patients with severe renal impairment, and patients with severe hepatic impairment [see Dosage and Administration (2.4) ]. Figure 3 Impact of Specific Population on the Pharmacokinetics of Paroxetine (log scale) Figure 1 Impact of Paroxetine on the Pharmacokinetics of Co-Administered Drugs (log scale) Figure 2 Impact of Co-Administered Drugs on the Pharmacokinetics of Paroxetine Figure 3 Impact of Specific Population on the Pharmacokinetics of Paroxetine (log scale)

12.1 Mechanism of Action The mechanism of action of paroxetine in the treatment of MDD, SAD, OCD\, PD, GAD, and PTSD is unknown, but is presumed to be linked to potentiation of serotonergic activity in the central nervous system resulting from inhibition of neuronal reuptake of serotonin (5-hydroxy-tryptamine, 5-HT).

12.2 Pharmacodynamics Studies at clinically relevant doses in humans have demonstrated that paroxetine blocks the uptake of serotonin into human platelets. In vitro studies in animals also suggest that paroxetine is a potent and highly selective inhibitor of neuronal serotonin reuptake (SSRI) and has only very weak effects on norepinephrine and dopamine neuronal reuptake.

12.3 Pharmacokinetics Nonlinearity in pharmacokinetics is observed with increasing doses of paroxetine. In a meta-analysis of paroxetine from 4 studies done in healthy volunteers following multiple dosing of 20 mg/day to 40 mg/day, males did not exhibit a significantly lower C max or AUC than females. Absorption Paroxetine hydrochloride is completely absorbed after oral dosing of a solution of the hydrochloride salt. In a study in which normal male subjects (n = 15) received 30 mg tablets daily for 30 days, steady-state paroxetine concentrations were achieved by approximately 10 days for most subjects, although it may take substantially longer in an occasional patient. At steady state, mean values of C max , T max , C min , and T ½ were 61.7 ng/mL (CV 45%), 5.2 hr. (CV 10%), 30.7 ng/mL (CV 67%), and 21.0 hours (CV 32%), respectively. The steady-state C max and C min values were about 6 and 14 times what would be predicted from single-dose studies. Steady-state drug exposure based on AUC 0-24 was about 8 times greater than would have been predicted from single-dose data in these subjects. The excess accumulation is a consequence of the fact that 1 of the enzymes that metabolizes paroxetine is readily saturable. Paroxetine is equally bioavailable from the oral suspension and tablet. Effect of Food The effects of food on the bioavailability of paroxetine were studied in subjects administered a single dose with and without food. AUC was only slightly increased (6%) when drug was administered with food but the C max was 29% greater, while the time to reach peak plasma concentration decreased from 6.4 hours post-dosing to 4.9 hours. Distribution Paroxetine distributes throughout the body, including the CNS, with only 1% remaining in the plasma. Approximately 95% and 93% of paroxetine is bound to plasma protein at 100 ng/mL and 400 ng/mL, respectively. Under clinical conditions, paroxetine concentrations would normally be less than 400 ng/mL. Paroxetine does not alter the in vitro protein binding of phenytoin or warfarin. Elimination Metabolism The mean elimination half-life is approximately 21 hours (CV 32%) after oral dosing of 30 mg tablets daily for 30 days of paroxetine. In steady-state dose proportionality studies involving elderly and nonelderly patients, at doses of 20 mg to 40 mg daily for the elderly and 20 mg to 50 mg daily for the nonelderly, some nonlinearity was observed in both populations, again reflecting a saturable metabolic pathway. In comparison to C min values after 20 mg daily, values after 40 mg daily were only about 2 to 3 times greater than doubled. Paroxetine is extensively metabolized after oral administration. The principal metabolites are polar and conjugated products of oxidation and methylation, which are readily cleared. Conjugates with glucuronic acid and sulfate predominate, and major metabolites have been isolated and identified. Data indicate that the metabolites have no more than 1/50 the potency of the parent compound at inhibiting serotonin uptake. The metabolism of paroxetine is accomplished in part by CYP2D6. Saturation of this enzyme at clinical doses appears to account for the nonlinearity of paroxetine kinetics with increasing dose and increasing duration of treatment. The role of this enzyme in paroxetine metabolism also suggests potential drug-drug interactions [see Drug Interactions (7) ].

omplished in part by CYP2D6. Saturation of this enzyme at clinical doses appears to account for the nonlinearity of paroxetine kinetics with increasing dose and increasing duration of treatment. The role of this enzyme in paroxetine metabolism also suggests potential drug-drug interactions [see Drug Interactions (7) ]. Pharmacokinetic behavior of paroxetine has not been evaluated in subjects who are deficient in CYP2D6 (poor metabolizers). Excretion Approximately 64% of a 30-mg oral solution dose of paroxetine was excreted in the urine with 2% as the parent compound and 62% as metabolites over a 10-day post-dosing period. About 36% was excreted in the feces (probably via the bile), mostly as metabolites and less than 1% as the parent compound over the 10-day post-dosing period. Drug Interaction Studies There are clinically significant, known drug interactions between paroxetine and other drugs [see Drug Interactions (7) ]. Figure 1 Impact of Paroxetine on the Pharmacokinetics of Co-Administered Drugs (log scale) Figure 2 Impact of Co-Administered Drugs on the Pharmacokinetics of Paroxetine Theophylline: Reports of elevated theophylline levels associated with paroxetine treatment have been reported. While this interaction has not been formally studied, it is recommended that theophylline levels be monitored when these drugs are concurrently administered. Drugs Metabolized by Cytochrome CYP3A4 An in vivo interaction study involving the co-administration under steady-state conditions of paroxetine and terfenadine, a substrate for CYP3A4, revealed no effect of paroxetine on terfenadine pharmacokinetics. In addition, in vitro studies have shown ketoconazole, a potent inhibitor of CYP3A4 activity, to be at least 100 times more potent than paroxetine as an inhibitor of the metabolism of several substrates for this enzyme, including terfenadine, triazolam, and cyclosporine. Paroxetine's extent of inhibition of CYP3A4 activity is not expected to be of clinical significance. Specific Populations The impact of specific populations on the pharmacokinetics of paroxetine are shown in Figure 3. The recommended starting dosage and maximum dosage of paroxetine is reduced in elderly patients, patients with severe renal impairment, and patients with severe hepatic impairment [see Dosage and Administration (2.4) ]. Figure 3 Impact of Specific Population on the Pharmacokinetics of Paroxetine (log scale) Figure 1 Impact of Paroxetine on the Pharmacokinetics of Co-Administered Drugs (log scale) Figure 2 Impact of Co-Administered Drugs on the Pharmacokinetics of Paroxetine Figure 3 Impact of Specific Population on the Pharmacokinetics of Paroxetine (log scale)

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Two-year carcinogenicity studies were conducted in rodents given paroxetine in the diet at 1 mg/kg/day, 5 mg/kg/day and 25 mg/kg/day (mice) and 1 mg/kg/day, 5 mg/kg/day and 20 mg/kg/day (rats). These doses are up to 2 (mouse) and 3 (rat) times the MRHD of 60 mg on a mg/m 2 basis. There was a significantly greater number of male rats in the high-dose group with reticulum cell sarcomas (1/100, 0/50, 0/50, and 4/50 for control, low-, middle-, and high-dose groups, respectively) and a significantly increased linear trend across dose groups for the occurrence of lymphoreticular tumors in male rats. Female rats were not affected. Although there was a dose-related increase in the number of tumors in mice, there was no drug-related increase in the number of mice with tumors. The relevance of these findings to humans is unknown. Mutagenesis Paroxetine produced no genotoxic effects in a battery of 5 in vitro and 2 in vivo assays that included the following: Bacterial mutation assay, mouse lymphoma mutation assay, unscheduled DNA synthesis assay, and tests for cytogenetic aberrations in vivo in mouse bone marrow and in vitro in human lymphocytes and in a dominant lethal test in rats. Impairment of Fertility A reduced pregnancy rate was found in reproduction studies in rats at a dose of paroxetine of 15 mg/kg/day, which is 2 times the MRHD of 60 mg on a mg/m 2 basis. Irreversible lesions occurred in the reproductive tract of male rats after dosing in toxicity studies for 2 weeks to 52 weeks. These lesions consisted of vacuolation of epididymal tubular epithelium at 50 mg/kg/day and atrophic changes in the seminiferous tubules of the testes with arrested spermatogenesis at 25 mg/kg/day (8 and 4 times the MRHD of 60 mg on a mg/m 2 basis).

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Two-year carcinogenicity studies were conducted in rodents given paroxetine in the diet at 1 mg/kg/day, 5 mg/kg/day and 25 mg/kg/day (mice) and 1 mg/kg/day, 5 mg/kg/day and 20 mg/kg/day (rats). These doses are up to 2 (mouse) and 3 (rat) times the MRHD of 60 mg on a mg/m 2 basis. There was a significantly greater number of male rats in the high-dose group with reticulum cell sarcomas (1/100, 0/50, 0/50, and 4/50 for control, low-, middle-, and high-dose groups, respectively) and a significantly increased linear trend across dose groups for the occurrence of lymphoreticular tumors in male rats. Female rats were not affected. Although there was a dose-related increase in the number of tumors in mice, there was no drug-related increase in the number of mice with tumors. The relevance of these findings to humans is unknown. Mutagenesis Paroxetine produced no genotoxic effects in a battery of 5 in vitro and 2 in vivo assays that included the following: Bacterial mutation assay, mouse lymphoma mutation assay, unscheduled DNA synthesis assay, and tests for cytogenetic aberrations in vivo in mouse bone marrow and in vitro in human lymphocytes and in a dominant lethal test in rats. Impairment of Fertility A reduced pregnancy rate was found in reproduction studies in rats at a dose of paroxetine of 15 mg/kg/day, which is 2 times the MRHD of 60 mg on a mg/m 2 basis. Irreversible lesions occurred in the reproductive tract of male rats after dosing in toxicity studies for 2 weeks to 52 weeks. These lesions consisted of vacuolation of epididymal tubular epithelium at 50 mg/kg/day and atrophic changes in the seminiferous tubules of the testes with arrested spermatogenesis at 25 mg/kg/day (8 and 4 times the MRHD of 60 mg on a mg/m 2 basis).

14 CLINICAL STUDIES 14.1 Major Depressive Disorder The efficacy of paroxetine as a treatment for major depressive disorder (MDD) has been established in 6 placebo-controlled studies of patients with MDD (aged 18 to 73). In these studies, paroxetine was shown to be statistically significantly more effective than placebo in treating MDD by at least 2 of the following measures: Hamilton Depression Rating Scale (HDRS), the Hamilton depressed mood item, and the Clinical Global Impression (CGI)-Severity of Illness. Paroxetine was statistically significantly better than placebo in improvement of the HDRS sub-factor scores, including the depressed mood item, sleep disturbance factor, and anxiety factor. Long-term efficacy of paroxetine for treatment of MDD in outpatients was demonstrated in a randomized withdrawal study. Patients who responded to paroxetine (HDRS total score < 8) during an initial 8-week open-label treatment phase were then randomized to continue paroxetine or placebo, for up to 1 year. Patients treated with paroxetine demonstrated a statistically significant lower relapse rate during the withdrawal phase (15%) compared to those on placebo (39%). Effectiveness was similar for male and female patients. 14.2 Obsessive Compulsive Disorder The effectiveness of paroxetine in the treatment of obsessive compulsive disorder (OCD) was demonstrated in two 12-week multicenter placebo-controlled studies of adult outpatients (Studies 1 and 2). Patients had moderate to severe OCD (DSM-IIIR) with mean baseline ratings on the Yale Brown Obsessive Compulsive Scale (YBOCS) total score ranging from 23 to 26. In study 1, a dose-range finding study, patients received fixed daily doses of paroxetine 20 mg, 40 mg, or 60 mg. Study 1 demonstrated that daily doses of paroxetine 40 mg and 60 mg are effective in the treatment of OCD. Patients receiving doses of paroxetine 40 mg and 60 mg experienced a mean reduction of approximately 6 and 7 points, respectively, on the YBOCS total score which was statistically significantly greater than the approximate 4-point reduction at 20 mg and a 3-point reduction in the placebo-treated patients. Study 2 was a flexible-dose study comparing paroxetine 20 mg to 60 mg daily with clomipramine 25 mg to 250 mg daily or placebo). In this study, patients receiving paroxetine experienced a mean reduction of approximately 7 points on the YBOCS total score, which was statistically significantly greater than the mean reduction of approximately 4 points in placebo-treated patients. The following table provides the outcome classification by treatment group on Global Improvement items of the Clinical Global Impression (CGI) scale for Study 1. Table 10 Outcome Classification (%) on CGI-Global Improvement Item for Completers in Study 1 in Patients with OCD Outcome Classification Placebo Paroxetine 20 mg Paroxetine 40 mg Paroxetine 60 mg (n = 74) (n = 75) (n = 66) (n = 66) % % % % Worse 14 7 7 3 No Change 44 35 22 19 Minimally Improved 24 33 29 34 Much Improved 11 18 22 24 Very Much Improved 7 7 20 20 Subgroup analyses did not indicate that there were any differences in treatment outcomes as a function of age or gender. The long-term efficacy of paroxetine for the treatment of OCD was established in a long-term extension to Study 1.

inimally Improved 24 33 29 34 Much Improved 11 18 22 24 Very Much Improved 7 7 20 20 Subgroup analyses did not indicate that there were any differences in treatment outcomes as a function of age or gender. The long-term efficacy of paroxetine for the treatment of OCD was established in a long-term extension to Study 1. Patients who responded to paroxetine during the 3-month double-blind phase and a 6-month extension on open-label paroxetine 20 mg to 60 mg daily were randomized to either paroxetine or placebo in a 6-month double-blind relapse prevention phase. Patients randomized to paroxetine were statistically significantly less likely to relapse than placebo-treated patients. 14.3 Panic Disorder The effectiveness of paroxetine in the treatment of panic disorder (PD) was demonstrated in three 10- to 12-week multicenter, placebo-controlled studies of adult outpatients (Studies 1, 2, and 3). Patients had PD (DSM-IIIR), with or without agoraphobia. In these studies, paroxetine was shown to be statistically significantly more effective than placebo in treating PD by at least 2 out of 3 measures of panic attack frequency and on the Clinical Global Impression Severity of Illness score. Study 1 was a 10-week dose-range finding study; patients received fixed doses of paroxetine 10 mg, 20 mg, or 40 mg daily or placebo. A statistically significant difference from placebo was observed only for the paroxetine 40 mg daily group. At endpoint, 76% of patients receiving paroxetine 40 mg daily were free of panic attacks, compared to 44% of placebo-treated patients. Study 2 was a 12-week flexible-dose study comparing paroxetine 10 mg to 60 mg daily and placebo. At endpoint, 51% of paroxetine-treated patients were free of panic attacks compared to 32% of placebo-treated patients. Study 3 was a 12-week flexible-dose study comparing paroxetine 10 mg to 60 mg daily to placebo in patients concurrently receiving standardized cognitive behavioral therapy. At endpoint, 33% of the paroxetine-treated patients showed a reduction to 0 or 1 panic attacks compared to 14% of placebo-treated patients. In Studies 2 and 3, the mean paroxetine dose for completers at endpoint was approximately 40 mg daily. Long-term efficacy of paroxetine in PD was demonstrated in an extension to Study 1. Patients who responded to paroxetine during the 10-week double-blind phase and during a 3-month double-blind extension phase were randomized to either paroxetine 10 mg, 20 mg, or 40 mg daily or placebo in a 3-month double-blind relapse prevention phase. Patients randomized to paroxetine were statistically significantly less likely to relapse than placebo-treated patients. Subgroup analyses did not indicate that there were any differences in treatment outcomes as a function of age or gender. 14.4 Social Anxiety Disorder The effectiveness of paroxetine in the treatment of social anxiety disorder (SAD) was demonstrated in three 12-week, multicenter, placebo-controlled studies (Studies 1, 2, and 3) of adult outpatients with SAD (DSM-IV). In these studies, the effectiveness of paroxetine compared to placebo was evaluated on the basis of (1) the proportion of responders, as defined by a Clinical Global Impression (CGI) Improvement score of 1 (very much improved) or 2 (much improved), and (2) change from baseline in the Liebowitz Social Anxiety Scale (LSAS). Studies 1 and 2 were flexible-dose studies comparing paroxetine 20 mg to 50 mg daily and placebo. Paroxetine demonstrated statistically significant superiority over placebo on both the CGI Improvement responder criterion and the Liebowitz Social Anxiety Scale (LSAS). In Study 1, for patients who completed to week 12, 69% of paroxetine-treated patients compared to 29% of placebo-treated patients were CGI Improvement responders.

emonstrated statistically significant superiority over placebo on both the CGI Improvement responder criterion and the Liebowitz Social Anxiety Scale (LSAS). In Study 1, for patients who completed to week 12, 69% of paroxetine-treated patients compared to 29% of placebo-treated patients were CGI Improvement responders. In Study 2, CGI Improvement responders were 77% and 42% for the paroxetine- and placebo-treated patients, respectively. Study 3 was a 12-week study comparing fixed doses of paroxetine 20 mg, 40 mg, or 60 mg daily with placebo. Paroxetine 20 mg was statistically significantly superior to placebo on both the LSAS Total Score and the CGI Improvement responder criterion; there were trends for superiority over placebo for the paroxetine 40 mg and 60 mg daily dose groups. There was no indication in this study of any additional benefit for doses higher than 20 mg daily. Subgroup analyses generally did not indicate differences in treatment outcomes as a function of age, race, or gender. 14.5 Generalized Anxiety Disorder The effectiveness of paroxetine in the treatment of generalized anxiety disorder (GAD) was demonstrated in two 8-week, multicenter, placebo-controlled studies (Studies 1 and 2) of adult outpatients with GAD (DSM-IV). Study 1 was an 8-week study comparing fixed doses of paroxetine 20 mg or 40 mg daily with placebo. Doses of paroxetine 20 mg or 40 mg were both demonstrated to be statistically significantly superior to placebo on the Hamilton Rating Scale for Anxiety (HAM-A) total score. There was not sufficient evidence in this study to suggest a greater benefit for the paroxetine 40 mg daily dose compared to the 20 mg daily dose. Study 2 was a flexible-dose study comparing paroxetine 20 mg to 50 mg daily and placebo. Paroxetine demonstrated statistically significant superiority over placebo on the Hamilton Rating Scale for Anxiety (HAM-A) total score. A third study, a flexible-dose study comparing paroxetine 20 mg to 50 mg daily to placebo, did not demonstrate statistically significant superiority of paroxetine over placebo on the Hamilton Rating Scale for Anxiety (HAM-A) total score, the primary outcome. Subgroup analyses did not indicate differences in treatment outcomes as a function of race or gender. There were insufficient elderly patients to conduct subgroup analyses on the basis of age. In a long-term trial, 566 patients meeting DSM-IV criteria for GAD, who had responded during a single-blind, 8-week acute treatment phase with paroxetine 20 mg to 50 mg daily, were randomized to continuation of paroxetine at their same dose, or to placebo, for up to 24 weeks of observation for relapse. Response during the single-blind phase was defined by having a decrease of ≥ 2 points compared to baseline on the CGI-Severity of Illness scale, to a score of ≤ 3. Relapse during the double-blind phase was defined as an increase of ≥ 2 points compared to baseline on the CGI-Severity of Illness scale to a score of ≥ 4, or withdrawal due to lack of efficacy. Patients continuing to receive paroxetine experienced a statistically significantly lower relapse rate over the subsequent 24 weeks compared to those receiving placebo. 14.6 Posttraumatic Stress Disorder The effectiveness of paroxetine in the treatment of Posttraumatic Stress Disorder (PTSD) was demonstrated in two 12-week, multicenter, placebo-controlled studies (Studies 1 and 2) of adult outpatients who met DSM-IV criteria for PTSD. The mean duration of PTSD symptoms for the 2 studies combined was 13 years (ranging from 0.1 year to 57 years). The percentage of patients with secondary MDD or non-PTSD anxiety disorders in the combined 2 studies was 41% (356 out of 858 patients) and 40% (345 out of 858 patients), respectively.

M-IV criteria for PTSD. The mean duration of PTSD symptoms for the 2 studies combined was 13 years (ranging from 0.1 year to 57 years). The percentage of patients with secondary MDD or non-PTSD anxiety disorders in the combined 2 studies was 41% (356 out of 858 patients) and 40% (345 out of 858 patients), respectively. Study outcome was assessed by (1) the Clinician-Administered PTSD Scale Part 2 (CAPS-2) score and (2) the Clinical Global Impression-Global Improvement Scale (CGI-I). The CAPS-2 is a multi-item instrument that measures 3 aspects of PTSD with the following symptom clusters: Reexperiencing/intrusion, avoidance/numbing and hyperarousal. The 2 primary outcomes for each trial were (1) change from baseline to endpoint on the CAPS-2 total score (17 items), and (2) proportion of responders on the CGI-I, where responders were defined as patients having a score of 1 (very much improved) or 2 (much improved). Study 1 was a 12-week study comparing fixed doses of paroxetine 20 mg or 40 mg daily to placebo. Doses of paroxetine 20 mg and 40 mg were demonstrated to be statistically significantly superior to placebo on change from baseline for the CAPS-2 total score and on proportion of responders on the CGI-I. There was not sufficient evidence in this study to suggest a greater benefit for the 40 mg daily dose compared to the 20 mg daily dose. Study 2 was a 12-week flexible-dose study comparing paroxetine 20 mg to 50 mg daily to placebo. Paroxetine was demonstrated to be significantly superior to placebo on change from baseline for the CAPS-2 total score and on proportion of responders on the CGI-I. A third study, a flexible-dose study comparing paroxetine 20 mg to 50 mg daily to placebo, demonstrated paroxetine to be statistically significantly superior to placebo on change from baseline for CAPS-2 total score, but not on proportion of responders on the CGI-I. The majority of patients in these trials were women (68% women: 377 out of 551 subjects in Study 1 and 66% women: 202 out of 303 subjects in Study 2). Subgroup analyses did not indicate differences in treatment outcomes as a function of gender. There were an insufficient number of patients who were 65 years and older or were non-Caucasian to conduct subgroup analyses on the basis of age or race, respectively.

<table ID="_RefID717" width="100%"><caption>Table 10 Outcome Classification (%) on CGI-Global Improvement Item for Completers in Study 1 in Patients with OCD</caption><col width="28%"/><col width="18%"/><col width="18%"/><col width="18%"/><col width="18%"/><tbody><tr><td styleCode="Rrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">Outcome Classification</content></paragraph></td><td align="center" styleCode="Rrule Toprule " valign="middle"><paragraph><content styleCode="bold">Placebo</content></paragraph></td><td align="center" styleCode="Rrule Toprule " valign="middle"><paragraph><content styleCode="bold">Paroxetine 20 mg</content></paragraph></td><td align="center" styleCode="Rrule Toprule " valign="middle"><paragraph><content styleCode="bold">Paroxetine 40 mg</content></paragraph></td><td align="center" styleCode="Rrule Toprule " valign="middle"><paragraph><content styleCode="bold">Paroxetine 60 mg</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule " valign="middle"/><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">(n = 74)</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">(n = 75)</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">(n = 66)</content></paragraph></td><td align="center" styleCode="Rrule " valign="middle"><paragraph><content styleCode="bold">(n = 66)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"/><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph><content styleCode="bold">%</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Worse</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>7</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>7</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>3</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>No Change</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>44</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>35</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>22</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>19</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Minimally Improved</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>24</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>33</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>29</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>34</paragraph></td><

ign="middle"><paragraph>24</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>33</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>29</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>34</paragraph></td>< /tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Much Improved</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>11</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>18</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>22</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>24</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="middle"><paragraph>Very Much Improved</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>7</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>7</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>20</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>20</paragraph></td></tr></tbody></table>

16 HOW SUPPLIED/STORAGE AND HANDLING Paroxetine Tablets USP, 10 mg are white to off-white, round-shaped, biconvex, film-coated tablets debossed with the logo of 'ZC, 15 and bisect' on one side and plain on other side, and are supplied as follows: Unit dose packages of 50 (5 x 10) NDC 68084-044-65 Unit dose packages of 100 (10 x 10) NDC 68084-044-01 Paroxetine Tablets USP, 20 mg are white to off-white, round-shaped, biconvex, film-coated tablets debossed with the logo of 'ZC, 16 and bisect' on one side and plain on other side, and are supplied as follows: Unit dose packages of 100 (10 x 10) NDC 68084-045-01 Paroxetine Tablets USP, 30 mg are white to off-white, round-shaped, biconvex, film-coated tablets debossed with the logo of 'ZC17' on one side and plain on other side, and are supplied as follows: Unit dose packages of 100 (10 x 10) NDC 68084-046-01 Paroxetine Tablets USP, 40 mg are white to off-white, round-shaped, biconvex, film-coated tablets debossed with the logo of 'ZC18' on one side and plain on other side, and are supplied as follows: Unit dose packages of 100 (10 x 10) NDC 68084-047-01 Store at 20°C to 25°C (68°F to 77°F) [See USP Controlled Room Temperature]. FOR YOUR PROTECTION: Do not use if blister is torn or broken.

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Suicidal Thoughts and Behaviors Advise patients and caregivers to look for the emergence of suicidality, especially early during treatment and when the dosage is adjusted up or down, and instruct them to report such symptoms to the healthcare provider [see Boxed Warning and Warnings and Precautions (5.1) ]. Serotonin Syndrome Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of paroxetine with other serotonergic drugs including triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, St. John's Wort, and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid). Instruct patients to contact their health care provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome [see Warnings and Precautions (5.2) , Drug Interactions (7) ]. Concomitant Medications Advise patients to inform their physician if they are taking, or plan to take, any prescription or over-the-counter drugs, since there is a potential for drug-drug interactions [see Warning and Precautions (5.3) , Drug Interactions (7) ]. Increased Risk of Bleeding Inform patients about the concomitant use of paroxetine with aspirin, NSAIDs, other antiplatelet drugs, warfarin, or other anticoagulants because the combined use has been associated with an increased risk of bleeding. Advise patients to inform their health care providers if they are taking or planning to take any prescription or over-the-counter medications that increase the risk of bleeding [see Warnings and Precautions (5.5) ]. Activation of Mania/Hypomania Advise patients and their caregivers to observe for signs of activation of mania/hypomania and instruct them to report such symptoms to the healthcare provider [see Warnings and Precautions (5.6) ]. Discontinuation Syndrome Advise patients not to abruptly discontinue paroxetine and to discuss any tapering regimen with their healthcare provider. Inform patients that adverse reactions can occur when paroxetine is discontinued [see Warnings and Precautions (5.7) ]. Sexual Dysfunction Advise patients that use of paroxetine may cause symptoms of sexual dysfunction in both male and female patients. Inform patients that they should discuss any changes in sexual function and potential management strategies with their healthcare provider [see Warnings and Precautions (5.13) ]. Allergic Reactions Advise patients to notify their healthcare provider if they develop an allergic reaction such as rash, hives, swelling, or difficulty breathing [see Adverse Reactions (6.1 , 6.2) ]. Embryo-Fetal Toxicity Advise women to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with paroxetine. Advise women of risks associated with first trimester use of paroxetine and that use later in pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, tube feeding and/or persistent pulmonary hypertension of the newborn (PPHN) [see Warnings and Precautions (5.4) , Use in Specific Populations (8.1) ].

ster use of paroxetine and that use later in pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, tube feeding and/or persistent pulmonary hypertension of the newborn (PPHN) [see Warnings and Precautions (5.4) , Use in Specific Populations (8.1) ]. Advise women that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to paroxetine during pregnancy [see Warnings and Precautions (5.4) , Use in Specific Populations (8.1) ] . Lactation Advise breastfeeding women using paroxetine to monitor infants for agitation, irritability, poor feeding and poor weight gain and to seek medical care if they notice these signs [see Use in Specific Populations (8.2) ] . Females and Males of Reproductive Potential Advise men that paroxetine may affect sperm quality, which may impair fertility; it is not known if this effect is reversible [see Use in Specific Populations (8.3) ] . To order more Medication Guides call American Health Packaging at 1-800-707-4621. Distributed by: American Health Packaging Columbus, OH 43217 8004401/0226(F)

Medication Guide 8004401/0226(F) Paroxetine (pa rox’ e teen) Tablets, USP What is the most important information I should know about paroxetine tablets? Paroxetine tablets can cause serious side effects, including: • Increased risk of suicidal thoughts or actions. Paroxetine tablets and other antidepressant medicines may increase suicidal thoughts and actions in some people 24 years of age and younger, especially within the first few months of treatment or when the dose is changed. Paroxetine tablets are not for use in children. o Depression or other mental illnesses are the most important causes of suicidal thoughts and actions. How can I watch for and try to prevent suicidal thoughts and actions? o Pay close attention to any changes, especially sudden changes in mood, behavior, thoughts or feelings or if you develop suicidal thoughts or actions. This is very important when an antidepressant medicine is started or when the does is changed. o Call your healthcare provider right away to report new or sudden changes in mood, behavior, thoughts or feelings or if you develop suicidal thoughts or actions. o Keep all follow-up visits with your healthcare provider as scheduled. Call your healthcare provider between visits as needed, especially if you have concerns about symptoms. Call your healthcare provider or get emergency medical help right away if you have any of the following symptoms, especially if they are new, worse, or worry you: o attempts to commit suicide o acting on dangerous impulses o acting aggressive or violent o thoughts about suicide or dying o new or worse depression o new or worse anxiety or panic attacks o feeling agitated, restless, angry, or irritableotrouble sleeping o an increase in activity and talking more than what is normal for you o other unusual changes in behavior or mood What are paroxetine tablets? Paroxetine tablets are prescription medicine used in adults to treat: •A certain type of depression called Major Depressive Disorder (MDD) •Obsessive Compulsive Disorder (OCD) •Panic Disorder (PD) •Social Anxiety Disorder (SAD) •Generalized Anxiety Disorder (GAD) •Posttraumatic Stress Disorder (PTSD) Do not take paroxetine tablets if you: •take a monoamine oxidase inhibitor (MAOI) •have stopped taking an MAOI in the last 14 days •are being treated with the antibiotic linezolid or the intravenous methylene blue •are taking pimozide •are taking thioridazine •are allergic to paroxetine or any of the ingredients in paroxetine tablets. See the end of this Medication Guide for a complete list of ingredients in paroxetine tablets. Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI or one of these medicines, including the antibiotic linezolid or intravenous methylene blue. Do not start taking an MAOI for at least 14 days after you stop treatment with paroxetine tablets. Before taking paroxetine tablets, tell your healthcare provider about all your medical conditions, including if you: •have heart problems •have or had bleeding problems •have, or have a family history of, bipolar disorder, mania or hypomania •have or had seizures or convulsions •have glaucoma (high pressure in the eye) •have low sodium levels in your blood •have bone problems •have kidney or liver problems •are pregnant or plan to become pregnant. Paroxetine tablets may harm your unborn baby.

r have a family history of, bipolar disorder, mania or hypomania •have or had seizures or convulsions •have glaucoma (high pressure in the eye) •have low sodium levels in your blood •have bone problems •have kidney or liver problems •are pregnant or plan to become pregnant. Paroxetine tablets may harm your unborn baby. o Taking paroxetine during your first trimester of pregnancy may cause your baby to be at an increased risk of having a heart problem (cardiac malformations) at birth. o Taking paroxetine during your third trimester of pregnancy may cause your baby to have breathing, temperature and feeding problems, low muscle tone and irritability after birth and may cause your baby to be at an increased risk of a serious lung problem at birth. Talk to your healthcare provider about the risk to your unborn baby if you take paroxetine during pregnancy. o Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with paroxetine. o There is a pregnancy registry for females who are exposed to paroxetine during pregnancy. The purpose of the registry is to collect information about the health of females exposed to paroxetine and their baby. If you become pregnant during treatment with paroxetine talk to your healthcare provider. •are breastfeeding or plan to breastfeed. Paroxetine passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with paroxetine tablets. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Paroxetine tablets and some other medicines may affect each other causing possible serious side effects. Paroxetine tablets may affect the way other medicines work and other medicines may affect the way paroxetine tablet works. Especially tell your healthcare provider if you take: •medicines used to treat migraine headaches called triptans •tricyclic antidepressants •lithium •tramadol, fentanyl, meperidine, methadone, or other opioids •tryptophan •buspirone •amphetamines •St. John’s Wort •medicines that can affect blood clotting such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin •diuretics •tamoxifen •medicines used to treat mood, anxiety, psychotic, or thought disorders, including selective serotonin reuptake (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) Ask your healthcare provider if you are not sure if you are taking any of these medicines. Your healthcare provider can tell you if it is safe to take paroxetine tablets with your other medicines. Do not start or stop any other medicines during treatment with paroxetine tablets without talking to your healthcare provider first. Stopping paroxetine tablets suddenly may cause you to have serious side effects. See, “What are the possible side effects of paroxetine tablets?” Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine. How should I take paroxetine tablets? •Take paroxetine tablets exactly as prescribed. Your healthcare provider may need to change the dose of paroxetine tablets until it is the right dose for you. • Take paroxetine tablet 1 time each day in the morning. • Paroxetine tablets may be taken with or without food. •If you take too much paroxetine tablets, call your poison control center at 1-800-222-1222 or go to the nearest hospital emergency room right away. What are possible side effects of paroxetine tablets? Paroxetine tablets can cause serious side effects, including: •See, “What is the most important information I should know about paroxetine tablets?” • Serotonin syndrome.

oison control center at 1-800-222-1222 or go to the nearest hospital emergency room right away. What are possible side effects of paroxetine tablets? Paroxetine tablets can cause serious side effects, including: •See, “What is the most important information I should know about paroxetine tablets?” • Serotonin syndrome. A potentially life-threatening problem called serotonin syndrome can happen when you take paroxetine tablets with certain other medicines. See, “Who should not take paroxetine tablets?” Call your healthcare provider or go to the nearest hospital emergency room right away if you have any of the following signs and symptoms of serotonin syndrome: o agitation o sweating o seeing or hearing things that are not real (hallucinations) o flushing o confusion o high body temperature (hyperthermia) o coma o shaking (tremors), stiff muscles, or muscle twitching o fast heart beat o loss of coordination o changes in blood pressure o seizures o dizziness o nausea, vomiting, diarrhea • Eye problems (angle-closure glaucoma). Paroxetine tablets may cause a type of eye problem called angle-closure glaucoma in people with certain other eye conditions. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are. Call your healthcare provider if you have eye pain, changes in your vision, or swelling or redness in or around the eye. • Medicine interactions. Taking paroxetine tablets with certain other medicines including thioridazine and pimozide may increase the risk of developing a serious heart problem called QT prolongation. • Seizures (convulsions). • Manic episodes. Manic episodes may happen in people with bipolar disorder who take paroxetine tablets. Symptoms may include: o greatly increased energy o severe problems sleeping o racing thoughts o reckless behavior o unusually grand ideas o excessive happiness or irritability o talking more or faster than usual • Discontinuation syndrome. Suddenly stopping paroxetine tablets may cause you to have serious side effects. Your healthcare provider may want to decrease your dose slowly. Symptoms may include: o nausea o electric shock feeling (paresthesia) o tiredness o sweating o tremor o problems sleeping o changes in your moodoanxiety o hypomaniaoirritability and agitation o confusion o ringing in your ears (tinnitus) o dizziness o headache o seizures • Low sodium levels in your blood (hyponatremia). Low sodium levels in your blood that may be serious and may cause death, can happen during treatment with paroxetine tablets. Elderly people and people who take certain medicines may be at a greater risk for developing low sodium levels in your blood. Signs and symptoms may include: o headache o difficulty concentrating o memory changes o confusion o weakness and unsteadiness on your feet which can lead to falls In more severe or more sudden cases, signs and symptoms include: o seeing or hearing things that are not real (hallucinations) o fainting o seizures o coma o stopping breathing (respiratory arrest) • Abnormal bleeding. Taking paroxetine tablets with aspirin, NSAIDs, or blood thinners may increase this risk. Tell your healthcare provider about any unusual bleeding or bruising. • Bone fractures. • Sexual problems (dysfunction). Taking selective serotonin reuptake inhibitors (SSRIs), including paroxetine, may cause sexual problems.

ing. Taking paroxetine tablets with aspirin, NSAIDs, or blood thinners may increase this risk. Tell your healthcare provider about any unusual bleeding or bruising. • Bone fractures. • Sexual problems (dysfunction). Taking selective serotonin reuptake inhibitors (SSRIs), including paroxetine, may cause sexual problems. Symptoms in males may include: o Delayed ejaculation or inability to have an ejaculation o Decreased sex drive o Problems getting or keeping an erection Symptoms in females may include: o Decreased sex drive o Delayed orgasm or inability to have an orgasm Talk to your healthcare provider if you develop any changes in your sexual function or if you have any questions or concerns about sexual problems during treatment with paroxetine. There may be treatments your healthcare provider can suggest. The most common side effects of paroxetine tablets include: • male and female sexual function problems •weakness (asthenia) • constipation •decreased appetite •diarrhea • dizziness •dry mouth • infection •problems sleeping • nausea •nervousness •sleepiness •sweating • shaking (tremor) •yawning These are not all the possible side effects of paroxetine tablets. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store paroxetine tablets? • Store paroxetine tablets between 68°F to 77°F (20°C to 25°C). Keep paroxetine tablets and all medicines out of the reach of children. General information about the safe and effective use of paroxetine tablets. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not take paroxetine tablets for a condition for which it was not prescribed. Do not give paroxetine tablets to other people, even if they have the same symptoms that you have. It may harm them. You may ask your healthcare provider or pharmacist for information about paroxetine tablets that is written for healthcare professionals. What are the ingredients in paroxetine tablets? Active ingredient: paroxetine hydrochloride, USP Inactive ingredients: dibasic calcium phosphate anhydrous, hypromellose 6 cP, lactose anhydrous, magnesium stearate, polyethylene glycol 6000, povidone, sodium starch glycolate, talc, and titanium dioxide. To order more Medication Guides call American Health Packaging at 1-800-707-4621. Distributed by: American Health Packaging Columbus, OH 43217 8004401/0226(F)

BOXED WARNING WARNING: SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors [see Warnings and Precautions ( 5.1 )]. Paroxetine is not approved for use in pediatric patients [see Use in Specific Populations ( 8.4 )]. WARNING: SUICIDAL THOUGHTS AND BEHAVIORS See full prescribing information for complete boxed warning. Increased risk of suicidal thoughts and behavior in pediatric and young adult patients taking antidepressants. Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors. Paroxetine is not approved for use in pediatric patients. ( 5.1 , 8.4 )

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1 INDICATIONS AND USAGE Paroxetine tablets are indicated in adults for the treatment of: Major depressive disorder (MDD) Obsessive compulsive disorder (OCD) Panic disorder (PD) Social anxiety disorder (SAD) Generalized anxiety disorder (GAD) Posttraumatic stress disorder (PTSD) Paroxetine is a selective serotonin reuptake inhibitor (SSRI) indicated in adults for the treatment of ( 1 ): Major Depressive Disorder (MDD) Obsessive Compulsive Disorder (OCD) Panic Disorder (PD) Social Anxiety Disorder (SAD) Generalized Anxiety Disorder (GAD) Posttraumatic Stress Disorder (PTSD)

2 DOSAGE AND ADMINISTRATION Recommended starting and maximum daily dosage for MDD, OCD, PD, and PTSD: ( 2.2 ) Indication Starting Daily Dose Maximum Daily Dose MDD 20 mg 50 mg OCD 20 mg 60 mg PD 10 mg 60 mg PTSD 20 mg 50 mg Recommended starting dosage for SAD and GAD is 20 mg daily. ( 2.3 ) Elderly patients, patients with severe renal impairment or severe hepatic impairment: Starting dosage is 10 mg daily. Maximum dosage is 40 mg daily. ( 2.4 ) When discontinuing paroxetine tablets, reduce dosage gradually. ( 2.6 , 5.7 ) 2.1 Administration Information Administer paroxetine tablets as a single daily dose in the morning, with or without food. 2.2 Recommended Dosage for MDD, OCD, PD, and PTSD The recommended starting dosages and maximum dosages of paroxetine tablets in patients with MDD, OCD, PD, and PTSD are presented in Table 1. In patients with an inadequate response, increase dosage in increments of 10 mg per day at intervals of at least 1 week, depending on tolerability. Table 1 Recommended Daily Dosage of Paroxetine Tablets in Patients with MDD, OCD, PD, and PTSD Indication Starting Dose Maximum Dose MDD 20 mg 50 mg OCD 20 mg 60 mg PD 10 mg 60 mg PTSD 20 mg 50 mg 2.3 Recommended Dosage for SAD and GAD SAD The starting and recommended dosage in patients with SAD is 20 mg daily. In clinical trials the effectiveness of paroxetine tablets was demonstrated in patients dosed in a range of 20 mg to 60 mg daily. While the safety of paroxetine tablets has been evaluated in patients with SAD at doses up to 60 mg daily, available information does not suggest any additional benefit for doses above 20 mg daily [see Clinical Studies ( 14.4 )]. GAD The starting and recommended dosage in patients with GAD is 20 mg daily. In clinical trials the effectiveness of paroxetine tablets in GAD was demonstrated in patients dosed in a range of 20 mg to 50 mg daily. There is not sufficient evidence to suggest a greater benefit to doses higher than 20 mg daily [see Clinical Studies ( 14.5 )]. In patients with an inadequate response, increase dosage in increments of 10 mg per day at intervals of at least 1 week, depending on tolerability. 2.4 Screen for Bipolar Disorder Prior to Starting Paroxetine Tablets Prior to initiating treatment with paroxetine tablets or another antidepressant, screen patients for a personal or family history of bipolar disorder, mania, or hypomania [see Warnings and Precautions ( 5.6 )]. 2.5 Recommended Dosage for Elderly Patients, Patients with Severe Renal Impairment, and Patients with Severe Hepatic Impairment The recommended initial dosage is 10 mg per day for elderly patients, patients with severe renal impairment, and patients with severe hepatic impairment. Dosage should not exceed 40 mg/day. 2.6 Switching Patients to or From a Monoamine Oxidase Inhibitor (MAOI) At least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI and initiation of paroxetine tablets. In addition, at least 14 days must elapse after stopping paroxetine before starting an MAOI antidepressant [see Contraindications ( 4 ), Warnings and Precautions ( 5.2 )]. 2.7 Discontinuation of Treatment With Paroxetine Tablets Adverse reactions may occur upon discontinuation of paroxetine tablets [see Warnings and Precautions ( 5.7 )]. Gradually reduce the dosage rather than stopping paroxetine abruptly whenever possible.

3 DOSAGE FORMS AND STRENGTHS Paroxetine tablets, USP are available as: 20 mg: White to off-white, round-shaped, biconvex, film- coated tablets debossed with the logo of 'ZC, 16 and bisect' on one side and plain on other side Tablets: 20 mg, scored tablets. ( 3 )

4 CONTRAINDICATIONS Paroxetine tablets are contraindicated in patients: Taking, or within 14 days of stopping, MAOIs (including the MAOIs linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [see Warnings and Precautions ( 5.2 ), Drug Interactions ( 7) ]. Taking thioridazine because of risk of QT prolongation [see Warnings and Precautions ( 5.3 , Drug Interactions ( 7 )] Taking pimozide because of risk of QT prolongation [see Warnings and Precautions ( 5.3 ), Drug Interactions ( 7 )]. With known hypersensitivity (e.g., anaphylaxis, angioedema, Stevens-Johnson syndrome) to paroxetine or any of the inactive ingredients in paroxetine tablets [ see Adverse Reactions ( 6.1 ), ( 6.2 )]. Concomitant use of monoamine oxidase inhibitors (MAOIs) or use within 14 days of discontinuing a MAOI. ( 4 , 5.3 , 7 ) Concomitant use of pimozide or thioridazine. ( 4 , 5.3 , 7 ) Known hypersensitivity to paroxetine or to any of the inactive ingredients in paroxetine tablets. ( 4 )

5 WARNINGS AND PRECAUTIONS Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents, but also when taken alone. If occurs, discontinue paroxetine and serotonergic agents and initiate supportive measures. ( 5.2 ) Embryofetal Toxicity: May cause fetal harm. Meta-analyses of epidemiological studies have shown increased risk (less than 2-fold) of cardiovascular malformations with exposure during the first trimester. ( 5.4 , 8.1 ) Increased Risk of Bleeding: Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, other antiplatelet drugs, warfarin, and other anticoagulant drugs may increase risk. ( 5.5 ) Activation of Mania/Hypomania: Screen patients for bipolar disorder. ( 5.6 ) Seizures: Use with caution in patients with seizure disorders. ( 5.8 ) Angle-Closure Glaucoma: Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants. ( 5.9 ) Sexual Dysfunction: paroxetine may cause symptoms of sexual dysfunction. ( 5.13 ) 5.1 Suicidal Thoughts and Behaviors in Adolescents and Young Adults In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater than in placebo-treated patients. There was considerable variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied. There were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with MDD. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1,000 patients treated are provided in Table 2. Table 2 Risk Differences of the Number of Patients with Suicidal Thoughts and Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients Age Range Drug-Placebo Difference in Number of Patients with Suicidal Thoughts and Behaviors per 1,000 Patients Treated Increases Compared to Placebo < 18 years old 14 additional cases 18 years to 24 years old 5 additional cases Decreases Compared to Placebo 25 years to 64 years old 1 fewer case ≥ 65 years old 6 fewer cases Paroxetine is not approved for use in pediatric patients. It is unknown whether the risk of suicidal thoughts and behaviors in children, adolescents, and young adults extends to longer-term use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with MDD that antidepressants delay the recurrence of depression and that depression itself is a risk factor for suicidal thoughts and behaviors. Monitor all antidepressant-treated patients for any indication for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy, and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing paroxetine, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.

l family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing paroxetine, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors. 5.2 Serotonin Syndrome SSRIs, including paroxetine, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines and St. John's Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [see Contraindications ( 4 ), Drug Interactions ( 7.1 )]. Serotonin syndrome can also occur when these drugs are used alone. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The concomitant use of paroxetine with MAOIs is contraindicated. In addition, do not initiate paroxetine in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection) or at lower doses. If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking paroxetine discontinue paroxetine before initiating treatment with the MAOI [see Contraindications ( 4 ), Drug Interactions ( 7 )]. Monitor all patients taking paroxetine for the emergence of serotonin syndrome. Discontinue treatment with paroxetine and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of paroxetine with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms. 5.3 Drug Interactions Leading to QT Prolongation The CYP2D6 inhibitory properties of paroxetine can elevate plasma levels of thioridazine and pimozide. Since thioridazine and pimozide given alone produce prolongation of the QTc interval and increase the risk of serious ventricular arrhythmias, the use of paroxetine is contraindicated in combination with thioridazine and pimozide [see Contraindications ( 4 ), Drug Interactions ( 7 ), Clinical Pharmacology ( 12.3 )]. 5.4 Embryofetal Toxicity Based on meta-analyses of epidemiological studies, exposure to paroxetine in the first trimester of pregnancy is associated with a less than 2-fold increase in the rate of cardiovascular malformations among infants. For women who intend to become pregnant or who are in their first trimester of pregnancy, paroxetine, should be initiated only after consideration of the other available treatment options [see Use in Specific Populations ( 8.1 )]. 5.5 Increased Risk of Bleeding Drugs that interfere with serotonin reuptake inhibition, including paroxetine, increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDS), other antiplatelet drugs, warfarin, and other anticoagulants may add to this risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding.

atory drugs (NSAIDS), other antiplatelet drugs, warfarin, and other anticoagulants may add to this risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Based on data from the published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Use in Specific Populations ( 8.1 )]. Bleeding events related to drugs that interfere with serotonin reuptake have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages. Inform patients about the increased risk of bleeding associated with the concomitant use of paroxetine and antiplatelet agents or anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio. 5.6 Activation of Mania or Hypomania In patients with bipolar disorder, treating a depressive episode with paroxetine or another antidepressant may precipitate a mixed/manic episode. During controlled clinical trials of paroxetine, hypomania or mania occurred in approximately 1% of paroxetine-treated unipolar patients compared to 1.1% of active-control and 0.3% of placebo-treated unipolar patients. Prior to initiating treatment with paroxetine, screen patients for any personal or family history of bipolar disorder, mania, or hypomania. 5.7 Discontinuation Syndrome Adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt discontinuation, include: nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia, such as electric shock sensations), tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible [see Dosage and Administration ( 2.7 )]. During clinical trials of GAD and PTSD, gradual decreases in the daily dose by 10 mg/day at weekly intervals followed by 1 week at 20 mg/day was used before treatment was discontinued. The following adverse reactions were reported at an incidence of 2% or greater for paroxetine and were at least twice that reported for placebo: Abnormal dreams, paresthesia, and dizziness adverse reactions have been reported upon discontinuation of treatment with paroxetine in pediatric patients. The safety and effectiveness of paroxetine in pediatric patients have not been established [see Boxed Warning , Warnings and Precautions ( 5.1 ), Use in Specific Populations ( 8.4 )]. 5.8 Seizures Paroxetine tablets have not been systematically evaluated in patients with seizure disorders. Patients with history of seizures were excluded from clinical studies. During clinical studies, seizures occurred in 0.1% of patients treated with paroxetine. Paroxetine should be prescribed with caution in patients with a seizure disorder. Discontinue paroxetine in any patient who develops seizures. 5.9 Angle-Closure Glaucoma The pupillary dilation that occurs following use of many antidepressant drugs including paroxetine may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy. Cases of angle-closure glaucoma associated with use of paroxetine have been reported. Avoid use of antidepressants, including paroxetine in patients with untreated anatomically narrow angles. 5.10 Hyponatremia Hyponatremia may occur as a result of treatment with SSRIs, including paroxetine. Cases with serum sodium lower than 110 mmol/L have been reported.

iated with use of paroxetine have been reported. Avoid use of antidepressants, including paroxetine in patients with untreated anatomically narrow angles. 5.10 Hyponatremia Hyponatremia may occur as a result of treatment with SSRIs, including paroxetine. Cases with serum sodium lower than 110 mmol/L have been reported. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls. Signs and symptoms associated with more severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). In patients with symptomatic hyponatremia, discontinue paroxetine and institute appropriate medical intervention. Elderly patients, patients taking diuretics, and those who are volume-depleted may be at greater risk of developing hyponatremia with SSRIs [see Use in Specific Populations ( 8.5 )]. 5.11 Reduction of Efficacy of Tamoxifen Some studies have shown that the efficacy of tamoxifen, as measured by the risk of breast cancer relapse/mortality, may be reduced with concomitant use of paroxetine as a result of paroxetine's irreversible inhibition of CYP2D6 and lower blood levels of tamoxifen [see Drug Interactions ( 7 )]. One study suggests that the risk may increase with longer duration of co-administration. However, other studies have failed to demonstrate such a risk. When tamoxifen is used for the treatment or prevention of breast cancer, prescribers should consider using an alternative antidepressant with little or no CYP2D6 inhibition. 5.12 Bone Fracture Epidemiological studies on bone fracture risk during exposure to some antidepressants, including SSRIs, have reported an association between antidepressant treatment and fractures. There are multiple possible causes for this observation and it is unknown to what extent fracture risk is directly attributable to SSRI treatment. 5.13 Sexual Dysfunction Use of SSRIs, including paroxetine, may cause symptoms of sexual dysfunction [see Adverse Reactions ( 6.1 )]. In male patients, SSRI use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction. In female patients, SSRI use may result in decreased libido and delayed or absent orgasm. It is important for prescribers to inquire about sexual function prior to initiation of paroxetine and to inquire specifically about changes in sexual function during treatment, because sexual function may not be spontaneously reported. When evaluating changes in sexual function, obtaining a detailed history (including timing of symptom onset) is important because sexual symptoms may have other causes, including the underlying psychiatric disorder. Discuss potential management strategies to support patients in making informed decisions about treatment.

<table ID="ID622" width="423" styleCode="Noautorules"><caption>Table 2 Risk Differences of the Number of Patients with Suicidal Thoughts and Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients</caption><col width="146"/><col width="277"/><tbody><tr><td align="center" styleCode="Lrule Toprule Botrule Rrule" valign="top"><content styleCode="bold">Age Range</content> </td><td align="center" styleCode=" Toprule Botrule Rrule" valign="top"><content styleCode="bold">Drug-Placebo Difference in Number of Patients with Suicidal Thoughts and Behaviors per 1,000 Patients Treated</content> </td></tr><tr><td align="center" styleCode="Lrule Botrule Rrule" valign="top"> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">Increases Compared to Placebo</content> </td></tr><tr><td align="center" styleCode="Lrule Botrule Rrule" valign="top">&lt; 18 years old </td><td align="center" styleCode=" Botrule Rrule" valign="top">14 additional cases </td></tr><tr><td align="center" styleCode="Lrule Botrule Rrule" valign="top">18 years to 24 years old </td><td align="center" styleCode=" Botrule Rrule" valign="top">5 additional cases </td></tr><tr><td styleCode="Lrule Botrule Rrule" valign="top"/><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">Decreases Compared to Placebo</content> </td></tr><tr><td align="center" styleCode="Lrule Botrule Rrule" valign="top">25 years to 64 years old </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 fewer case </td></tr><tr><td align="center" styleCode="Lrule Botrule Rrule" valign="top">&#x2265; 65 years old </td><td align="center" styleCode=" Botrule Rrule" valign="top">6 fewer cases </td></tr></tbody></table>

6 ADVERSE REACTIONS The following adverse reactions are included in more detail in other sections of the prescribing information: Hypersensitivity reactions to paroxetine [see Contraindications ( 4 )] Suicidal Thoughts and Behaviors [see Warnings and Precautions ( 5.1 )] Serotonin Syndrome [see Warnings and Precautions ( 5.2 )] Embryofetal Toxicity [see Warnings and Precautions ( 5.4 )] Increased Risk of Bleeding [see Warnings and Precautions ( 5.5 )] Activation of Mania/Hypomania [see Warnings and Precautions ( 5.6 )] Discontinuation Syndrome [see Warnings and Precautions ( 5.7 )] Seizures [see Warnings and Precautions ( 5.8 )] Angle-closure Glaucoma [see Warnings and Precautions ( 5.9 )] Hyponatremia [see Warnings and Precautions ( 5.10 )] Bone Fracture [see Warnings and Precautions ( 5.12 )] Sexual Dysfunction [see Warnings and Precautions ( 5.13 )] Most common adverse reactions (≥ 5% and at least twice placebo) are abnormal ejaculation, asthenia, constipation, decreased appetite, diarrhea, dizziness, dry mouth, female genital disorder, impotence, infection, insomnia, libido decreased, male genital disorder, nausea, nervousness, somnolence, sweating, tremor, yawn. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data for paroxetine are from: 6-week clinical trials in MDD patients who received paroxetine 20 mg to 50 mg once daily 12-week clinical trials in OCD patients who received paroxetine 20 mg to 60 mg once daily 10- to 12-week clinical trials in PD patients who received paroxetine 10 mg to 60 mg once daily 12-week clinical trials in SAD patients who received paroxetine 20 mg to 50 mg once daily 8-week clinical trials in GAD patients who received paroxetine 10 mg to 50 mg once daily 12-week clinical trials in PTSD patients who received paroxetine 20 mg to 50 mg once daily Adverse Reactions Leading to Discontinuation Twenty percent (1,199/6,145) of patients treated with paroxetine in clinical trials in MDD and 16.1% (84/522), 11.8% (64/542), 9.4% (44/469), 10.7% (79/735), and 11.7% (79/676) of patients treated with paroxetine in clinical trials in SAD, OCD, PD, GAD, and PTSD, respectively, discontinued treatment due to an adverse reaction. The most common adverse reactions (≥ 1%) associated with discontinuation (i.e., those adverse reactions associated with dropout at a rate approximately twice or greater for paroxetine compared to placebo) are presented in Table 3. Table 3 Adverse Reactions Reported as Leading to Discontinuation (≥ 1% of Paroxetine-Treated Patients and Greater than Placebo) in MDD, OCD, PD, SAD, GAD, and PTSD Trials Where numbers are not provided the incidence of the adverse reactions in patients treated with paroxetine was not > 1% or was not greater than or equal to 2 times the incidence of placebo. a. Incidence corrected for gender.

Paroxetine-Treated Patients and Greater than Placebo) in MDD, OCD, PD, SAD, GAD, and PTSD Trials Where numbers are not provided the incidence of the adverse reactions in patients treated with paroxetine was not > 1% or was not greater than or equal to 2 times the incidence of placebo. a. Incidence corrected for gender. MDD OCD PD SAD GAD PTSD Paroxetine Placebo Paroxetine Placebo Paroxetine Placebo Paroxetine Placebo Paroxetine Placebo Paroxetine Placebo % % % % % % % % % % % % CNS Somnolence 2.3 0.7 - 1.9 0.3 3.4 0.3 2 0.2 2.8 0.6 Insomnia - - 1.7 0 1.3 0.3 3.1 0 - - Agitation 1.1 0.5 - - - Tremor 1.1 0.3 - 1.7 0 1 0.2 Anxiety - - - 1.1 0 - - Dizziness - - 1.5 0 1.9 0 1 0.2 - - Gastrointestinal Constipation - 1.1 0 - - Nausea 3.2 1.1 1.9 0 3.2 1.2 4 0.3 2 0.2 2.2 0.6 Diarrhea 1 0.3 - Dry Mouth 1 0.3 - - - Vomiting 1 0.3 - 1 0 - - Flatulence 1 0.3 - - Other Asthenia 1.6 0.4 1.9 0.4 2.5 0.6 1.8 0.2 1.6 0.2 Abnormal Ejaculation a 1.6 0 2.1 0 4.9 0.6 2.5 0.5 - - Sweating 1 0.3 - 1.1 0 1.1 0.2 - - Impotence a - 1.5 0 - - Libido Decreased 1 0 - - Most Common Adverse Reactions The most commonly observed adverse reactions associated with the use of paroxetine (incidence of 5% or greater and at least twice that for placebo) were: MDD: Asthenia, sweating, nausea, decreased appetite, somnolence, dizziness, insomnia, tremor, nervousness, ejaculatory disturbance, and other male genital disorders. OCD: Nausea, dry mouth, decreased appetite, constipation, dizziness, somnolence, tremor, sweating, impotence, and abnormal ejaculation. PD: Asthenia, sweating, decreased appetite, libido decreased, tremor, abnormal ejaculation, female genital disorders, and impotence. SAD: Sweating, nausea, dry mouth, constipation, decreased appetite, somnolence, tremor, libido decreased, yawn, abnormal ejaculation, female genital disorders, and impotence. GAD: Asthenia, infection, constipation, decreased appetite, dry mouth, nausea, libido decreased, somnolence, tremor, sweating, and abnormal ejaculation. PTSD: Asthenia, sweating, nausea, dry mouth, diarrhea, decreased appetite, somnolence, libido decreased, abnormal ejaculation, female genital disorders, and impotence. Adverse Reactions in Patients with MDD Table 4 presents the adverse reactions that occurred at an incidence of 1% or more and greater than placebo in clinical trials of paroxetine-treated patients with MDD. Table 4 Adverse Reactions (≥ l% of Paroxetine-Treated Patients and Greater than Placebo) in 6-Week Clinical Trials for MDD a Includes mostly "lump in throat" and "tightness in throat." b Percentage corrected for gender.

e of 1% or more and greater than placebo in clinical trials of paroxetine-treated patients with MDD. Table 4 Adverse Reactions (≥ l% of Paroxetine-Treated Patients and Greater than Placebo) in 6-Week Clinical Trials for MDD a Includes mostly "lump in throat" and "tightness in throat." b Percentage corrected for gender. c Mostly "ejaculatory delay." d Includes "anorgasmia," "erectile difficulties," "delayed ejaculation/orgasm," and "sexual dysfunction," and "impotence." e Includes mostly "difficulty with micturition" and "urinary hesitancy." f Includes mostly "anorgasmia" and "difficulty reaching climax/orgasm." Body System/ Adverse Reaction Paroxetine (n = 421) % Placebo (n = 421) % Body as a Whole Headache 18 17 Asthenia 15 6 Cardiovascular Palpitation 3 1 Vasodilation 3 1 Dermatologic Sweating 11 2 Rash 2 1 Gastrointestinal Nausea 26 9 Dry Mouth 18 12 Constipation 14 9 Diarrhea 12 8 Decreased Appetite 6 2 Flatulence 4 2 Oropharynx Disorder a 2 0 Dyspepsia 2 1 Musculoskeletal Myopathy 2 1 Myalgia 2 1 Myasthenia 1 0 Nervous System Somnolence 23 9 Dizziness 13 6 Insomnia 13 6 Tremor 8 2 Nervousness 5 3 Anxiety 5 3 Paresthesia 4 2 Libido Decreased 3 0 Drugged Feeling 2 1 Confusion 1 0 Respiration Yawn 4 0 Special Senses Blurred Vision 4 1 Taste Perversion 2 0 Urogenital System Ejaculatory Disturbance b,c 13 0 Other Male Genital Disorders b,d 10 0 Urinary Frequency 3 1 Urination Disorder e 3 0 Female Genital Disorders b,f 2 0 Adverse Reactions in Patients with OCD, PD, and SAD Table 5 presents adverse reactions that occurred at a frequency of 2% or more in clinical trials in patients with OCD, PD, and SAD. Table 5 Adverse Reactions (≥ 2% of Paroxetine-Treated Patients and Greater than Placebo) in 10 to 12-Week Clinical Trials for OCD, PD, and SAD a . Percentage corrected for gender. Body System/Preferred Term Obsessive Compulsive Disorder Panic Disorder Social Anxiety Disorder Paroxetine Placebo Paroxetine Placebo Paroxetine Placebo (n = 542) (n = 265) (n = 469) (n = 324) (n = 425) (n = 339) % % % % % % Body as a Whole Asthenia 22 14 14 5 22 14 Abdominal Pain - - 4 3 - - Chest Pain 3 2 - - - - Back Pain - - 3 2 - - Chills 2 1 2 1 - - Trauma - - - - 3 1 Cardiovascular Vasodilation 4 1 - - - - Palpitation 2 0 - - - - Dermatologic Sweating 9 3 14 6 9 2 Rash 3 2 - - - - Gastrointestinal Nausea 23 10 23 17 25 7 Dry Mouth 18 9 18 11 9 3 Constipation 16 6 8 5 5 2 Diarrhea 10 10 12 7 9 6 Decreased Appetite 9 3 7 3 8 2 Dyspepsia - - - - 4 2 Flatulence - - - - 4 2 Increased Appetite 4 3 2 1 - - Vomiting - - - - 2 1 Musculoskeletal Myalgia - - - - 4 3 Nervous System Insomnia 24 13 18 10 21 16 Somnolence 24 7 19 11 22 5 Dizziness 12 6 14 10 11 7 Tremor 11 1 9 1 9 1 Nervousness 9 8 - - 8 7 Libido Decreased 7 4 9 1 12 1 Agitation - - 5 4 3 1 Anxiety - - 5 4 5 4 Abnormal Dreams 4 1 - - - - Concentration Impaired 3 2 - - 4 1 Depersonalization 3 0 - - - - Myoclonus 3 0 3 2 2 1 Amnesia 2 1 - - - - Respiratory System Rhinitis - - 3 0 - - Pharyngitis - - - - 4 2 Yawn - - - - 5 1 Special Senses Abnormal Vision 4 2 - - 4 1 Taste Perversion 2 0 - - - - Urogenital System Abnormal Ejaculation a 23 1 21 1 28 1 Dysmenorrhea - - - - 5 4 Female Genital Disorders a 3 0 9 1 9 1 Impotence a 8 1 5 0 5 1 Urinary Frequency 3 1 2 0 - - Urination Impaired 3 0 - - - - Urinary Tract Infection 2 1 2 1 - - Adverse Reactions in Patients with GAD and PTSD Table 6 presents adverse reactions that occurred at a frequency of 2% or more in clinical trials in patients with GAD and PTSD. Table 6 Adverse Reactions (≥ 2% of Paroxetine-Treated Patients and Greater than Placebo) in 8- to 12-Week Clinical Trials for GAD and PTSD a a. Percentage corrected for gender.

th GAD and PTSD Table 6 presents adverse reactions that occurred at a frequency of 2% or more in clinical trials in patients with GAD and PTSD. Table 6 Adverse Reactions (≥ 2% of Paroxetine-Treated Patients and Greater than Placebo) in 8- to 12-Week Clinical Trials for GAD and PTSD a a. Percentage corrected for gender. Body System/Preferred Term Generalized Anxiety Disorder Posttraumatic Stress Disorder Paroxetine Placebo Paroxetine Placebo (n = 735) (n = 529) (n = 676) (n = 504) % % % % Body as a Whole Asthenia 14 6 12 4 Headache 17 14 - - Infection 6 3 5 4 Abdominal Pain 4 3 Trauma 6 5 Cardiovascular Vasodilation 3 1 2 1 Dermatologic Sweating 6 2 5 1 Gastrointestinal Nausea 20 5 19 8 Dry Mouth 11 5 10 5 Constipation 10 2 5 3 Diarrhea 9 7 11 5 Decreased Appetite 5 1 6 3 Vomiting 3 2 3 2 Dyspepsia - - 5 3 Nervous System Insomnia 11 8 12 11 Somnolence 15 5 16 5 Dizziness 6 5 6 5 Tremor 5 1 4 1 Nervousness 4 3 - - Libido Decreased 9 2 5 2 Abnormal Dreams 3 Respiratory System Respiratory Disorder 7 5 - - Sinusitis 4 3 - - Yawn 4 - 2 < 1 Special Senses Abnormal Vision 2 1 3 1 Urogenital System Abnormal Ejaculation a 25 2 13 2 Female Genital Disorder a 4 1 5 1 Impotence a 4 3 9 1 Dose Dependent Adverse Reactions MDD A comparison of adverse reaction rates in a fixed-dose study comparing paroxetine 10 mg, 20 mg, 30 mg, and 40 mg once daily with placebo in the treatment of MDD revealed dose dependent adverse reactions, as shown in Table 7. Table 7 Adverse Reactions (≥ 5% of Paroxetine-Treated Patients and ≥ Twice the Rate of Placebo) (in a Dose-Comparison Trial in the Treatment of MDD) Body System/Preferred Term Placebo Paroxetine n=51 10 mg n=102 20 mg n=104 30 mg n=101 40 mg n=102 % % % % % Body as a Whole Asthenia 0 2.9 10.6 13.9 12.7 Dermatology Sweating 2 1 6.7 8.9 11.8 Gastrointestinal Constipation 5.9 4.9 7.7 9.9 12.7 Decreased Appetite 2 2 5.8 4 4.9 Diarrhea 7.8 9.8 19.2 7.9 14.7 Dry Mouth 2 10.8 18.3 15.8 20.6 Nausea 13.7 14.7 26.9 34.7 36.3 Nervous System Anxiety 0 2 5.8 5.9 5.9 Dizziness 3.9 6.9 6.7 8.9 12.7 Nervousness 0 5.9 5.8 4 2.9 Paresthesia 0 2.9 1 5 5.9 Somnolence 7.8 12.7 18.3 20.8 21.6 Tremor 0 0 7.7 7.9 14.7 Special Senses Blurred Vision 2 2.9 2.9 2 7.8 Urogenital System Abnormal Ejaculation 0 5.8 6.5 10.6 13 Impotence 0 1.9 4.3 6.4 1.9 Male Genital Disorders 0 3.8 8.7 6.4 3.7 OCD In a fixed-dose study comparing placebo and paroxetine 20 mg, 40 mg, and 60 mg in the treatment of OCD, there was no clear relationship between adverse reactions and the dose of paroxetine to which patients were assigned. PD In a fixed-dose study comparing placebo and paroxetine 10 mg, 20 mg, and 40 mg in the treatment of PD, the following adverse reactions were shown to be dose-dependent: asthenia, dry mouth, anxiety, libido decreased, tremor, and abnormal ejaculation. SAD In a fixed-dose study comparing placebo and paroxetine 20 mg, 40 mg and 60 mg in the treatment of SAD, for most of the adverse reactions, there was no clear relationship between adverse reactions and the dose of paroxetine to which patients were assigned. GAD In a fixed-dose study comparing placebo and paroxetine 20 mg and 40 mg in the treatment of GAD, the following adverse reactions were shown to be dose-dependent: asthenia, constipation, and abnormal ejaculation. PTSD In a fixed-dose study comparing placebo and paroxetine 20 mg and 40 mg in the treatment of PTSD, the following adverse reactions were shown to be dose-dependent: impotence and abnormal ejaculation. Male and Female Sexual Dysfunction Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of SSRI treatment.

is; rare: Abortion, breast atrophy, breast enlargement, endometrial disorder, epididymitis, female lactation, fibrocystic breast, kidney calculus, kidney pain, leukorrhea, mastitis, metrorrhagia, nephritis, oliguria, salpingitis, urethritis, urinary casts, uterine spasm, urolith, vaginal hemorrhage, vaginal moniliasis. 6.2 Postmarketing Experience The following reactions have been identified during post approval use of paroxetine. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Acute pancreatitis, elevated liver function tests (the most severe cases were deaths due to liver necrosis, and grossly elevated transaminases associated with severe liver dysfunction), Guillain-Barr¡SR syndrome, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), syndrome of inappropriate ADH secretion, prolactinemia and galactorrhea; extrapyramidal symptoms which have included akathisia, bradykinesia, cogwheel rigidity, oculogyric crisis which has been associated with concomitant use of pimozide; status epilepticus, acute renal failure, pulmonary hypertension, allergic alveolitis, anosmia, hyposmia, anaphylaxis, eclampsia, laryngismus, optic neuritis, porphyria, restless legs syndrome (RLS), ventricular fibrillation, ventricular tachycardia (including torsade de pointes), hemolytic anemia, events related to impaired hematopoiesis (including aplastic anemia, pancytopenia, bone marrow aplasia, and agranulocytosis), vasculitic syndromes (such as Henoch-Schönlein purpura), and premature births in pregnant women. There has been a case report of severe hypotension when paroxetine was added to chronic metoprolol treatment.

<table ID="ID655" width="0" styleCode="Noautorules"><caption>Table 3 Adverse Reactions Reported as Leading to Discontinuation (&#x2265; 1% of Paroxetine-Treated Patients and Greater than Placebo) in MDD, OCD, PD, SAD, GAD, and PTSD Trials</caption><col width="110"/><col width="73"/><col width="53"/><col width="73"/><col width="53"/><col width="73"/><col width="53"/><col width="73"/><col width="53"/><col width="73"/><col width="53"/><col width="73"/><col width="53"/><tfoot><tr><td align="left" colspan="13"><paragraph styleCode="Footnote">Where numbers are not provided the incidence of the adverse reactions in patients treated with paroxetine was not &gt; 1% or was not greater than or equal to 2 times the incidence of placebo.</paragraph></td></tr><tr><td align="left" colspan="13"><paragraph styleCode="Footnote">^a.Incidence corrected for gender.

re numbers are not provided the incidence of the adverse reactions in patients treated with paroxetine was not &gt; 1% or was not greater than or equal to 2 times the incidence of placebo.</paragraph></td></tr><tr><td align="left" colspan="13"><paragraph styleCode="Footnote">^a.Incidence corrected for gender. </paragraph></td></tr></tfoot><tbody><tr><td styleCode="Lrule Toprule Rrule" valign="top"/><td colspan="2" align="center" styleCode=" Toprule Botrule Rrule" valign="top"><content styleCode="bold">MDD</content> </td><td colspan="2" align="center" styleCode=" Toprule Botrule Rrule" valign="top"><content styleCode="bold">OCD</content> </td><td colspan="2" align="center" styleCode=" Toprule Botrule Rrule" valign="top"><content styleCode="bold">PD</content> </td><td colspan="2" align="center" styleCode=" Toprule Botrule Rrule" valign="top"><content styleCode="bold">SAD</content> </td><td colspan="2" align="center" styleCode=" Toprule Botrule Rrule" valign="top"><content styleCode="bold">GAD</content> </td><td colspan="2" align="center" styleCode=" Toprule Botrule Rrule" valign="top"><content styleCode="bold">PTSD</content> </td></tr><tr><td styleCode="Lrule Botrule Rrule" valign="top"/><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">Paroxetine</content> </td><td align="center" styleCode=" Toprule Botrule Rrule" valign="top"><content styleCode="bold">Placebo</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">Paroxetine</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">Placebo</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">Paroxetine</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">Placebo</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">Paroxetine</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">Placebo</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">Paroxetine</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">Placebo</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">Paroxetine</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">Placebo</content> </td></tr><tr><td styleCode="Lrule Botrule Rrule" valign="top"/><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td></t

tent> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td></t r><tr><td align="left" styleCode=" Lrule Rrule"><content styleCode="bold">CNS</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode=" Lrule Rrule">Somnolence </td><td align="center" styleCode=" Rrule" valign="top">2.3 </td><td align="center" styleCode=" Rrule" valign="top">0.7 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td styleCode=" Rrule" valign="top"/><td align="center" styleCode=" Rrule" valign="top">1.9 </td><td align="center" styleCode=" Rrule" valign="top">0.3 </td><td align="center" styleCode=" Rrule" valign="top">3.4 </td><td align="center" styleCode=" Rrule" valign="top">0.3 </td><td align="center" styleCode=" Rrule" valign="top">2 </td><td align="center" styleCode=" Rrule" valign="top">0.2 </td><td align="center" styleCode=" Rrule" valign="top">2.8 </td><td align="center" styleCode=" Rrule" valign="top">0.6 </td></tr><tr><td align="left" styleCode=" Lrule Rrule">Insomnia </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">1.7 </td><td align="center" styleCode=" Rrule" valign="top">0 </td><td align="center" styleCode=" Rrule" valign="top">1.3 </td><td align="center" styleCode=" Rrule" valign="top">0.3 </td><td align="center" styleCode=" Rrule" valign="top">3.1 </td><td align="center" styleCode=" Rrule" valign="top">0 </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td></tr><tr><td align="left" styleCode=" Lrule Rrule">Agitation </td><td align="center" styleCode=" Rrule" valign="top">1.1 </td><td align="center" styleCode=" Rrule" valign="top">0.5 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td></tr><tr><td align="left" styleCode=" Lrule Rrule">Tremor </td><td align="center" styleCode=" Rrule" valign="top">1.1 </td><td align="center" styleCode=" Rrule" valign="top">0.3 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td align="center" styleCode=" Rrule" valign="top">1.7 </td><td align="center" styleCode=" Rrule" valign="top">0 </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">0.2 </td></tr><tr><td align="left" styleCode=" Lrule Rrule">Anxiety </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="cent

"top"/><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">0.2 </td></tr><tr><td align="left" styleCode=" Lrule Rrule">Anxiety </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="cent er" styleCode=" Rrule" valign="top">- </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td align="center" styleCode=" Rrule" valign="top">1.1 </td><td align="center" styleCode=" Rrule" valign="top">0 </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule">Dizziness </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">1.5 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td><td styleCode=" Botrule Rrule" valign="top"/><td styleCode=" Botrule Rrule" valign="top"/><td align="center" styleCode=" Botrule Rrule" valign="top">1.9 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td></tr><tr><td align="left" styleCode=" Lrule Rrule"><content styleCode="bold">Gastrointestinal</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode=" Lrule Rrule">Constipation </td><td align="center" styleCode=" Rrule" valign="top">- </td><td styleCode=" Rrule" valign="top"/><td align="center" styleCode=" Rrule" valign="top">1.1 </td><td align="center" styleCode=" Rrule" valign="top">0 </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td></tr><tr><td align="left" styleCode=" Lrule Rrule">Nausea </td><td align="center" styleCode=" Rrule" valign="top">3.2 </td><td align="center" styleCode=" Rrule" valign="top">1.1 </td><td align="center" styleCode=" Rrule" valign="top">1.9 </td><td align="center" styleCode=" Rrule" valign="top">0 </td><td align="center" styleCode=" Rrule" valign="top">3.2 </td><td align="center" styleCode=" Rrule" valign="top">1.2 </td><td align="center" styleCode=" Rrule" valign="top">4 </td><td align="center" styleCode=" Rrule" valign="top">0.3 </td><td align="center" styleCode=" Rrule" valign="top">2 </td><td align="center" styleCode=" Rrule" valign="top">0.2 </td><td align="center" styleCode=" Rrule" valign="top">2.2 </td><td align="center" styleCode=" Rrule" valign="top">0.6 </td></tr><tr><td align="left" styleCode=" Lrule Rrule">Diarrhea </td><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">0.3 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td styleCode=" Rr

><td align="center" styleCode=" Rrule" valign="top">0.6 </td></tr><tr><td align="left" styleCode=" Lrule Rrule">Diarrhea </td><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">0.3 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td styleCode=" Rr ule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode=" Lrule Rrule">Dry Mouth </td><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">0.3 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td></tr><tr><td align="left" styleCode=" Lrule Rrule">Vomiting </td><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">0.3 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">0 </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule">Flatulence </td><td styleCode=" Botrule Rrule" valign="top"/><td styleCode=" Botrule Rrule" valign="top"/><td styleCode=" Botrule Rrule" valign="top"/><td styleCode=" Botrule Rrule" valign="top"/><td styleCode=" Botrule Rrule" valign="top"/><td styleCode=" Botrule Rrule" valign="top"/><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.3 </td><td styleCode=" Botrule Rrule" valign="top"/><td styleCode=" Botrule Rrule" valign="top"/><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td></tr><tr><td align="left" styleCode=" Lrule Rrule"><content styleCode="bold">Other</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode=" Lrule Rrule">Asthenia </td><td align="center" styleCode=" Rrule" valign="top">1.6 </td><td align="center" styleCode=" Rrule" valign="top">0.4 </td><td align="center" styleCode=" Rrule" valign="top">1.9 </td><td align="center" styleCode=" Rrule" valign="top">0.4 </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td align="center" styleCode=" Rrule" valign="top">2.5 </td><td align="center" styleCode=" Rrule" valign="top">0.6 </td><td align="center" styleCode=" Rrule" valign="top">1.8 </td><td align="center" styleCode=" Rrule" valign="top">0.2 </td><td align="center" styleCode=" Rrule" valign="top

yleCode=" Rrule" valign="top"/><td align="center" styleCode=" Rrule" valign="top">2.5 </td><td align="center" styleCode=" Rrule" valign="top">0.6 </td><td align="center" styleCode=" Rrule" valign="top">1.8 </td><td align="center" styleCode=" Rrule" valign="top">0.2 </td><td align="center" styleCode=" Rrule" valign="top ">1.6 </td><td align="center" styleCode=" Rrule" valign="top">0.2 </td></tr><tr><td align="left" styleCode=" Lrule Rrule">Abnormal Ejaculation ^a </td><td align="center" styleCode=" Rrule" valign="top">1.6 </td><td align="center" styleCode=" Rrule" valign="top">0 </td><td align="center" styleCode=" Rrule" valign="top">2.1 </td><td align="center" styleCode=" Rrule" valign="top">0 </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td align="center" styleCode=" Rrule" valign="top">4.9 </td><td align="center" styleCode=" Rrule" valign="top">0.6 </td><td align="center" styleCode=" Rrule" valign="top">2.5 </td><td align="center" styleCode=" Rrule" valign="top">0.5 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Sweating </td><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">0.3 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td align="center" styleCode=" Rrule" valign="top">1.1 </td><td align="center" styleCode=" Rrule" valign="top">0 </td><td align="center" styleCode=" Rrule" valign="top">1.1 </td><td align="center" styleCode=" Rrule" valign="top">0.2 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td></tr><tr><td align="left" styleCode=" Lrule Rrule">Impotence ^a </td><td align="center" styleCode=" Rrule" valign="top">- </td><td styleCode=" Rrule" valign="top"/><td align="center" styleCode=" Rrule" valign="top">1.5 </td><td align="center" styleCode=" Rrule" valign="top">0 </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Libido Decreased </td><td styleCode=" Botrule Rrule" valign="top"/><td styleCode=" Botrule Rrule" valign="top"/><td styleCode=" Botrule Rrule" valign="top"/><td styleCode=" Botrule Rrule" valign="top"/><td styleCode=" Botrule Rrule" valign="top"/><td styleCode=" Botrule Rrule" valign="top"/><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td><td styleCode=" Botrule Rrule" valign="top"/><td styleCode=" Botrule Rrule" valign="top"/><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td></tr></tbody></table>

op">1 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td><td styleCode=" Botrule Rrule" valign="top"/><td styleCode=" Botrule Rrule" valign="top"/><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td></tr></tbody></table> <table ID="ID657" width="639" styleCode="Noautorules"><caption>Table 4 Adverse Reactions (&#x2265; l% of Paroxetine-Treated Patients and Greater than Placebo) in 6-Week Clinical Trials for MDD</caption><col width="213"/><col width="213"/><col width="213"/><tfoot><tr><td align="left" colspan="3"><paragraph styleCode="Footnote">^aIncludes mostly &quot;lump in throat&quot; and &quot;tightness in throat.&quot; </paragraph></td></tr><tr><td align="left" colspan="3"><paragraph styleCode="Footnote">^bPercentage corrected for gender.

"213"/><col width="213"/><tfoot><tr><td align="left" colspan="3"><paragraph styleCode="Footnote">^aIncludes mostly &quot;lump in throat&quot; and &quot;tightness in throat.&quot; </paragraph></td></tr><tr><td align="left" colspan="3"><paragraph styleCode="Footnote">^bPercentage corrected for gender. </paragraph></td></tr><tr><td align="left" colspan="3"><paragraph styleCode="Footnote">^cMostly &quot;ejaculatory delay.&quot; </paragraph></td></tr><tr><td align="left" colspan="3"><paragraph styleCode="Footnote">^dIncludes &quot;anorgasmia,&quot; &quot;erectile difficulties,&quot; &quot;delayed ejaculation/orgasm,&quot; and &quot;sexual dysfunction,&quot; and &quot;impotence.&quot; </paragraph></td></tr><tr><td align="left" colspan="3"><paragraph styleCode="Footnote">^eIncludes mostly &quot;difficulty with micturition&quot; and &quot;urinary hesitancy.&quot; </paragraph></td></tr><tr><td align="left" colspan="3"><paragraph styleCode="Footnote">^fIncludes mostly &quot;anorgasmia&quot; and &quot;difficulty reaching climax/orgasm.&quot; </paragraph></td></tr></tfoot><tbody><tr><td align="center" styleCode="Lrule Toprule Rrule" valign="top"><content styleCode="bold">Body System/</content> <content styleCode="bold">Adverse Reaction</content> </td><td align="center" styleCode=" Toprule Rrule" valign="top"><content styleCode="bold">Paroxetine</content> <content styleCode="bold">(n = 421)</content> <content styleCode="bold">%</content> </td><td align="center" styleCode=" Toprule Rrule" valign="top"><content styleCode="bold">Placebo</content> <content styleCode="bold">(n = 421)</content> <content styleCode="bold">%</content> </td></tr><tr><td align="left" styleCode="Lrule Toprule Rrule" valign="top"><content styleCode="bold">Body as a Whole</content> </td><td align="center" styleCode=" Toprule Rrule" valign="top"> </td><td align="center" styleCode=" Toprule Rrule" valign="top"> </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Headache </td><td align="center" styleCode=" Rrule" valign="top">18 </td><td align="center" styleCode=" Rrule" valign="top">17 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Asthenia </td><td align="center" styleCode=" Botrule Rrule" valign="top">15 </td><td align="center" styleCode=" Botrule Rrule" valign="top">6 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Cardiovascular</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Palpitation </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td align="center" styleCode=" Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Vasodilation </td><td align="center" styleCode=" Botrule Rrule" valign="top">3 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Dermatologic</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Sweating </td><td align="center" styleCode=" Rrule" valign="top">11 </td><td align="center" styleCode=" Rrule" valign="top">2 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Rash </td><td align="center" styleCode=" Botrule Rrule" valign="top">2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Gastrointestinal</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode

e" valign="top">2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Gastrointestinal</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode =" Lrule Rrule" valign="top">Nausea </td><td align="center" styleCode=" Rrule" valign="top">26 </td><td align="center" styleCode=" Rrule" valign="top">9 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Dry Mouth </td><td align="center" styleCode=" Rrule" valign="top">18 </td><td align="center" styleCode=" Rrule" valign="top">12 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Constipation </td><td align="center" styleCode=" Rrule" valign="top">14 </td><td align="center" styleCode=" Rrule" valign="top">9 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Diarrhea </td><td align="center" styleCode=" Rrule" valign="top">12 </td><td align="center" styleCode=" Rrule" valign="top">8 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Decreased Appetite </td><td align="center" styleCode=" Rrule" valign="top">6 </td><td align="center" styleCode=" Rrule" valign="top">2 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Flatulence </td><td align="center" styleCode=" Rrule" valign="top">4 </td><td align="center" styleCode=" Rrule" valign="top">2 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Oropharynx Disorder ^a </td><td align="center" styleCode=" Rrule" valign="top">2 </td><td align="center" styleCode=" Rrule" valign="top">0 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Dyspepsia </td><td align="center" styleCode=" Botrule Rrule" valign="top">2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Musculoskeletal</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Myopathy </td><td align="center" styleCode=" Rrule" valign="top">2 </td><td align="center" styleCode=" Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Myalgia </td><td align="center" styleCode=" Rrule" valign="top">2 </td><td align="center" styleCode=" Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Myasthenia </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Nervous System</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Somnolence </td><td align="center" styleCode=" Rrule" valign="top">23 </td><td align="center" styleCode=" Rrule" valign="top">9 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Dizziness </td><td align="center" styleCode=" Rrule" valign="top">13 </td><td align="center" styleCode=" Rrule" valign="top">6 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Insomnia </td><td align="center" styleCode=" Rrule" valign="top">13 </td><td align="center" styleCode=" Rrule" valign="top">6 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Tremor </td><td align="center" styleCode=" Rrule" valign="top">8 </td><td align="center" styleCode=" Rrule" valign="top">2 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Nervousness </td><td align="center" styleCode=" Rrule" valign="top">5 </td><

align="left" styleCode=" Lrule Rrule" valign="top">Tremor </td><td align="center" styleCode=" Rrule" valign="top">8 </td><td align="center" styleCode=" Rrule" valign="top">2 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Nervousness </td><td align="center" styleCode=" Rrule" valign="top">5 </td>< td align="center" styleCode=" Rrule" valign="top">3 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Anxiety </td><td align="center" styleCode=" Rrule" valign="top">5 </td><td align="center" styleCode=" Rrule" valign="top">3 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Paresthesia </td><td align="center" styleCode=" Rrule" valign="top">4 </td><td align="center" styleCode=" Rrule" valign="top">2 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Libido Decreased </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td align="center" styleCode=" Rrule" valign="top">0 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Drugged Feeling </td><td align="center" styleCode=" Rrule" valign="top">2 </td><td align="center" styleCode=" Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Confusion </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Respiration</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Yawn </td><td align="center" styleCode=" Botrule Rrule" valign="top">4 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Special Senses</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Blurred Vision </td><td align="center" styleCode=" Rrule" valign="top">4 </td><td align="center" styleCode=" Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Taste Perversion </td><td align="center" styleCode=" Botrule Rrule" valign="top">2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Urogenital System</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Ejaculatory Disturbance ^b,c </td><td align="center" styleCode=" Rrule" valign="top">13 </td><td align="center" styleCode=" Rrule" valign="top">0 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Other Male Genital Disorders ^b,d </td><td align="center" styleCode=" Rrule" valign="top">10 </td><td align="center" styleCode=" Rrule" valign="top">0 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Urinary Frequency </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td align="center" styleCode=" Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Urination Disorder ^e </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td align="center" styleCode=" Rrule" valign="top">0 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Female Genital Disorders ^b,f </td><td align="center" styleCode=" Botrule Rrule" valign="top">2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td></tr></tbody></table>

gn="center" styleCode=" Rrule" valign="top">0 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Female Genital Disorders ^b,f </td><td align="center" styleCode=" Botrule Rrule" valign="top">2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td></tr></tbody></table> <table ID="ID659" width="0" styleCode="Noautorules"><caption>Table 5 Adverse Reactions (&#x2265; 2% of Paroxetine-Treated Patients and Greater than Placebo) in 10 to 12-Week Clinical Trials for OCD, PD, and SAD</caption><col width="155"/><col width="88"/><col width="78"/><col width="88"/><col width="75"/><col width="88"/><col width="82"/><tfoot><tr><td align="left" colspan="7"><paragraph styleCode="Footnote">^a. Percentage corrected for gender.

ater than Placebo) in 10 to 12-Week Clinical Trials for OCD, PD, and SAD</caption><col width="155"/><col width="88"/><col width="78"/><col width="88"/><col width="75"/><col width="88"/><col width="82"/><tfoot><tr><td align="left" colspan="7"><paragraph styleCode="Footnote">^a. Percentage corrected for gender. </paragraph></td></tr></tfoot><tbody><tr><td rowspan="3" align="left" styleCode="Lrule Toprule Rrule" valign="top"><content styleCode="bold">Body</content> <content styleCode="bold">System/Preferred</content> <content styleCode="bold">Term</content> </td><td colspan="2" align="center" styleCode=" Toprule Botrule Rrule" valign="top"><content styleCode="bold">Obsessive Compulsive</content> <content styleCode="bold">Disorder</content> </td><td colspan="2" align="center" styleCode=" Toprule Botrule Rrule" valign="top"><content styleCode="bold">Panic Disorder</content> </td><td colspan="2" align="center" styleCode=" Toprule Botrule Rrule" valign="top"><content styleCode="bold">Social Anxiety</content> <content styleCode="bold">Disorder</content> </td></tr><tr><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">Paroxetine</content> </td><td align="center" styleCode=" Toprule Rrule" valign="top"><content styleCode="bold">Placebo</content> </td><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">Paroxetine</content> </td><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">Placebo</content> </td><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">Paroxetine</content> </td><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">Placebo</content> </td></tr><tr><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">(n = 542)</content> </td><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">(n = 265)</content> </td><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">(n = 469)</content> </td><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">(n = 324)</content> </td><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">(n = 425)</content> </td><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">(n = 339)</content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Body as a Whole</content> </td><td align="left" styleCode=" Rrule" valign="top"> </td><td align="left" styleCode=" Rrule" valign="top"> </td><td align="left" styleCode=" Rrule" valign="top"> </td><td align="left" styleCode=" Rrule" valign="top"> </td><td align="left" styleCode=" Rrule" valign="top"> </td><td align="left" styleCode=" Rrule" valign="top"> </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Asthenia </td><td align="center" styleCode=" Rrule" valign="top">22 </td><td align="center" styleCode=" Rrule" valign="top">14 </td><td align="center" styleCode=" Rrule" valign="top">14 </td><td align="center" styleCode=" Rrule" valign="top">5 </td><td align="center" styleCode=" Rrule" valign

Lrule Rrule" valign="top">Asthenia </td><td align="center" styleCode=" Rrule" valign="top">22 </td><td align="center" styleCode=" Rrule" valign="top">14 </td><td align="center" styleCode=" Rrule" valign="top">14 </td><td align="center" styleCode=" Rrule" valign="top">5 </td><td align="center" styleCode=" Rrule" valign ="top">22 </td><td align="center" styleCode=" Rrule" valign="top">14 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Abdominal Pain </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">4 </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Chest Pain </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td align="center" styleCode=" Rrule" valign="top">2 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Back Pain </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td align="center" styleCode=" Rrule" valign="top">2 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Chills </td><td align="center" styleCode=" Rrule" valign="top">2 </td><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">2 </td><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Trauma </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">3 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Cardiovascular</content> </td><td align="left" styleCode=" Rrule" valign="top"> </td><td align="left" styleCode=" Rrule" valign="top"> </td><td align="left" styleCode=" Rrule" valign="top"> </td><td align="left" styleCode=" Rrule" valign="top"> </td><td align="left" styleCode=" Rrule" valign="top"> </td><td align="left" styleCode=" Rrule" valign="top"> </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Vasodilation </td><td align="center" styleCode=" Rrule" valign="top">4 </td><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Palpitation </td><td align="center" styleCode=" Botrule Rrule" valign="top">2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td

"Lrule Botrule Rrule" valign="top">Palpitation </td><td align="center" styleCode=" Botrule Rrule" valign="top">2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Dermatologic</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Sweating </td><td align="center" styleCode=" Rrule" valign="top">9 </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td align="center" styleCode=" Rrule" valign="top">14 </td><td align="center" styleCode=" Rrule" valign="top">6 </td><td align="center" styleCode=" Rrule" valign="top">9 </td><td align="center" styleCode=" Rrule" valign="top">2 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Rash </td><td align="center" styleCode=" Botrule Rrule" valign="top">3 </td><td align="center" styleCode=" Botrule Rrule" valign="top">2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Gastrointestinal</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Nausea </td><td align="center" styleCode=" Rrule" valign="top">23 </td><td align="center" styleCode=" Rrule" valign="top">10 </td><td align="center" styleCode=" Rrule" valign="top">23 </td><td align="center" styleCode=" Rrule" valign="top">17 </td><td align="center" styleCode=" Rrule" valign="top">25 </td><td align="center" styleCode=" Rrule" valign="top">7 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Dry Mouth </td><td align="center" styleCode=" Rrule" valign="top">18 </td><td align="center" styleCode=" Rrule" valign="top">9 </td><td align="center" styleCode=" Rrule" valign="top">18 </td><td align="center" styleCode=" Rrule" valign="top">11 </td><td align="center" styleCode=" Rrule" valign="top">9 </td><td align="center" styleCode=" Rrule" valign="top">3 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Constipation </td><td align="center" styleCode=" Rrule" valign="top">16 </td><td align="center" styleCode=" Rrule" valign="top">6 </td><td align="center" styleCode=" Rrule" valign="top">8 </td><td align="center" styleCode=" Rrule" valign="top">5 </td><td align="center" styleCode=" Rrule" valign="top">5 </td><td align="center" styleCode=" Rrule" valign="top">2 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Diarrhea </td><td align="center" styleCode=" Rrule" valign="top">10 </td><td align="center" styleCode=" Rrule" valign="top">10 </td><td align="center" styleCode=" Rrule" valign="top">12 </td><td align="center" styleCode=" Rrule" valign="top">7 </td><td align="center" styleCode=" Rrule" valign="top">9 </td><td align="center" styleCode=" Rrule" valign="top">6 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">D

valign="top">10 </td><td align="center" styleCode=" Rrule" valign="top">12 </td><td align="center" styleCode=" Rrule" valign="top">7 </td><td align="center" styleCode=" Rrule" valign="top">9 </td><td align="center" styleCode=" Rrule" valign="top">6 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">D ecreased Appetite </td><td align="center" styleCode=" Rrule" valign="top">9 </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td align="center" styleCode=" Rrule" valign="top">7 </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td align="center" styleCode=" Rrule" valign="top">8 </td><td align="center" styleCode=" Rrule" valign="top">2 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Dyspepsia </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">4 </td><td align="center" styleCode=" Rrule" valign="top">2 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Flatulence </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">4 </td><td align="center" styleCode=" Rrule" valign="top">2 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Increased Appetite </td><td align="center" styleCode=" Rrule" valign="top">4 </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td align="center" styleCode=" Rrule" valign="top">2 </td><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Vomiting </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Musculoskeletal</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Myalgia </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">4 </td><td align="center" styleCode=" Botrule Rrule" valign="top">3 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Nervous System</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Insomnia </td><td align="center" styleCode=" Rrule" valign="top">24 </td><td align="center" styleCode=" Rrule" valign="top">13 <

e" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Insomnia </td><td align="center" styleCode=" Rrule" valign="top">24 </td><td align="center" styleCode=" Rrule" valign="top">13 < /td><td align="center" styleCode=" Rrule" valign="top">18 </td><td align="center" styleCode=" Rrule" valign="top">10 </td><td align="center" styleCode=" Rrule" valign="top">21 </td><td align="center" styleCode=" Rrule" valign="top">16 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Somnolence </td><td align="center" styleCode=" Rrule" valign="top">24 </td><td align="center" styleCode=" Rrule" valign="top">7 </td><td align="center" styleCode=" Rrule" valign="top">19 </td><td align="center" styleCode=" Rrule" valign="top">11 </td><td align="center" styleCode=" Rrule" valign="top">22 </td><td align="center" styleCode=" Rrule" valign="top">5 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Dizziness </td><td align="center" styleCode=" Rrule" valign="top">12 </td><td align="center" styleCode=" Rrule" valign="top">6 </td><td align="center" styleCode=" Rrule" valign="top">14 </td><td align="center" styleCode=" Rrule" valign="top">10 </td><td align="center" styleCode=" Rrule" valign="top">11 </td><td align="center" styleCode=" Rrule" valign="top">7 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Tremor </td><td align="center" styleCode=" Rrule" valign="top">11 </td><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">9 </td><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">9 </td><td align="center" styleCode=" Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Nervousness </td><td align="center" styleCode=" Rrule" valign="top">9 </td><td align="center" styleCode=" Rrule" valign="top">8 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">8 </td><td align="center" styleCode=" Rrule" valign="top">7 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Libido Decreased </td><td align="center" styleCode=" Rrule" valign="top">7 </td><td align="center" styleCode=" Rrule" valign="top">4 </td><td align="center" styleCode=" Rrule" valign="top">9 </td><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">12 </td><td align="center" styleCode=" Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Agitation </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">5 </td><td align="center" styleCode=" Rrule" valign="top">4 </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td align="center" styleCode=" Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Anxiety </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">5 </td><td align="center" styleCode=" Rrule" valign="top">4 </td><td align="center" styleCode=" Rrule" valign="top">5 </td><td align="center" styleCode=" Rrule" valign="top">4 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Abnormal Dreams </td><td align="center" styleCode=" Rrule" valign="top">4 </td><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">- </

</td><td align="center" styleCode=" Rrule" valign="top">4 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Abnormal Dreams </td><td align="center" styleCode=" Rrule" valign="top">4 </td><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">- </ td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Concentration Impaired </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td align="center" styleCode=" Rrule" valign="top">2 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">4 </td><td align="center" styleCode=" Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Depersonalization </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td align="center" styleCode=" Rrule" valign="top">0 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Myoclonus </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td align="center" styleCode=" Rrule" valign="top">0 </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td align="center" styleCode=" Rrule" valign="top">2 </td><td align="center" styleCode=" Rrule" valign="top">2 </td><td align="center" styleCode=" Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Amnesia </td><td align="center" styleCode=" Botrule Rrule" valign="top">2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Respiratory System</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Rhinitis </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td align="center" styleCode=" Rrule" valign="top">0 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Pharyngitis </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">4 </td><td align="center" styleCode=" Rrule" valign="top">2 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Yawn </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">-

left" styleCode="Lrule Botrule Rrule" valign="top">Yawn </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">5 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Special Senses</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Abnormal Vision </td><td align="center" styleCode=" Rrule" valign="top">4 </td><td align="center" styleCode=" Rrule" valign="top">2 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">4 </td><td align="center" styleCode=" Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Taste Perversion </td><td align="center" styleCode=" Botrule Rrule" valign="top">2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Urogenital System</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Abnormal Ejaculation ^a </td><td align="center" styleCode=" Rrule" valign="top">23 </td><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">21 </td><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">28 </td><td align="center" styleCode=" Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Dysmenorrhea </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">5 </td><td align="center" styleCode=" Rrule" valign="top">4 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Female Genital Disorders ^a </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td align="center" styleCode=" Rrule" valign="top">0 </td><td align="center" styleCode=" Rrule" valign="top">9 </td><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">9 </td><td align="center" styleCode=" Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Impotence ^a </td><td align="center" styleCode=" Rrule" valign="top">8 </td><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">5 </td><td align="center" styleCode=" Rrule" valign="top">0 </td><td align="center" styleCode=" Rrule" valign="top">5 </td><td align="center" styleCode=" Rr

align="center" styleCode=" Rrule" valign="top">8 </td><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">5 </td><td align="center" styleCode=" Rrule" valign="top">0 </td><td align="center" styleCode=" Rrule" valign="top">5 </td><td align="center" styleCode=" Rr ule" valign="top">1 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Urinary Frequency </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">2 </td><td align="center" styleCode=" Rrule" valign="top">0 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Urination Impaired </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td align="center" styleCode=" Rrule" valign="top">0 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Urinary Tract Infection </td><td align="center" styleCode=" Botrule Rrule" valign="top">2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td><td align="center" styleCode=" Botrule Rrule" valign="top">2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td></tr></tbody></table> <table ID="ID661" width="472" styleCode="Noautorules"><caption>Table 6 Adverse Reactions (&#x2265; 2% of Paroxetine-Treated Patients and Greater than Placebo) in 8- to 12-Week Clinical Trials for GAD and PTSD ^a</caption><col width="135"/><col width="92"/><col width="76"/><col width="93"/><col width="76"/><tfoot><tr><td align="left" colspan="5"><paragraph styleCode="Footnote">^a.Percentage corrected for gender.

e-Treated Patients and Greater than Placebo) in 8- to 12-Week Clinical Trials for GAD and PTSD ^a</caption><col width="135"/><col width="92"/><col width="76"/><col width="93"/><col width="76"/><tfoot><tr><td align="left" colspan="5"><paragraph styleCode="Footnote">^a.Percentage corrected for gender. </paragraph></td></tr></tfoot><tbody><tr><td rowspan="4" align="left" styleCode="Lrule Toprule Botrule Rrule" valign="top"><content styleCode="bold">Body</content> <content styleCode="bold">System/Preferred Term</content> </td><td colspan="2" align="center" styleCode=" Toprule Botrule Rrule" valign="top"><content styleCode="bold">Generalized Anxiety</content> <content styleCode="bold">Disorder</content> </td><td colspan="2" align="center" styleCode=" Toprule Botrule Rrule" valign="top"><content styleCode="bold">Posttraumatic Stress</content> <content styleCode="bold">Disorder</content> </td></tr><tr><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">Paroxetine</content> </td><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">Placebo</content> </td><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">Paroxetine</content> </td><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">Placebo</content> </td></tr><tr><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">(n = 735)</content> </td><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">(n = 529)</content> </td><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">(n = 676)</content> </td><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">(n = 504)</content> </td></tr><tr><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Body as a</content> <content styleCode="bold">Whole</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Asthenia </td><td align="center" styleCode=" Rrule" valign="top">14 </td><td align="center" styleCode=" Rrule" valign="top">6 </td><td align="center" styleCode=" Rrule" valign="top">12 </td><td align="center" styleCode=" Rrule" valign="top">4 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Headache </td><td align="center" styleCode=" Rrule" valign="top">17 </td><td align="center" styleCode=" Rrule" valign="top">14 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Infection </td><td align="center" styleCode=" Rrule" valign="top">6 </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td align="center" styleCode=" Rrule" valign="top">5 </td><td align="center" styleCode=" Rrule" valign="top">4 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Abdominal Pain </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td align="center" styleCode=" Rrule" valign="top">4 </td><td align="center" styleCode=" Rrule" valign="top">3 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Trauma </td><td styleCode=" Botrule Rrule" valign="top"/><td styleCo

Code=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td align="center" styleCode=" Rrule" valign="top">4 </td><td align="center" styleCode=" Rrule" valign="top">3 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Trauma </td><td styleCode=" Botrule Rrule" valign="top"/><td styleCo de=" Botrule Rrule" valign="top"/><td align="center" styleCode=" Botrule Rrule" valign="top">6 </td><td align="center" styleCode=" Botrule Rrule" valign="top">5 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Cardiovascular</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Vasodilation </td><td align="center" styleCode=" Botrule Rrule" valign="top">3 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td><td align="center" styleCode=" Botrule Rrule" valign="top">2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Dermatologic</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Sweating </td><td align="center" styleCode=" Botrule Rrule" valign="top">6 </td><td align="center" styleCode=" Botrule Rrule" valign="top">2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">5 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Gastrointestinal</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Nausea </td><td align="center" styleCode=" Rrule" valign="top">20 </td><td align="center" styleCode=" Rrule" valign="top">5 </td><td align="center" styleCode=" Rrule" valign="top">19 </td><td align="center" styleCode=" Rrule" valign="top">8 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Dry Mouth </td><td align="center" styleCode=" Rrule" valign="top">11 </td><td align="center" styleCode=" Rrule" valign="top">5 </td><td align="center" styleCode=" Rrule" valign="top">10 </td><td align="center" styleCode=" Rrule" valign="top">5 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Constipation </td><td align="center" styleCode=" Rrule" valign="top">10 </td><td align="center" styleCode=" Rrule" valign="top">2 </td><td align="center" styleCode=" Rrule" valign="top">5 </td><td align="center" styleCode=" Rrule" valign="top">3 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Diarrhea </td><td align="center" styleCode=" Rrule" valign="top">9 </td><td align="center" styleCode=" Rrule" valign="top">7 </td><td align="center" styleCode=" Rrule" valign="top">11 </td><td align="center" styleCode=" Rrule" valign="top">5 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Decreased Appetite </td><td align="center" styleCode=" Rrule" valign="top">5 </td><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">6 </td><td align="center" styleCode=" Rrule" valign="top">3 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Vomiting </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td align="center" styleCode=" Rrule" valign="top">2 </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td ali

td><td align="center" styleCode=" Rrule" valign="top">3 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Vomiting </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td align="center" styleCode=" Rrule" valign="top">2 </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td ali gn="center" styleCode=" Rrule" valign="top">2 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Dyspepsia </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">5 </td><td align="center" styleCode=" Botrule Rrule" valign="top">3 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Nervous System</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Insomnia </td><td align="center" styleCode=" Rrule" valign="top">11 </td><td align="center" styleCode=" Rrule" valign="top">8 </td><td align="center" styleCode=" Rrule" valign="top">12 </td><td align="center" styleCode=" Rrule" valign="top">11 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Somnolence </td><td align="center" styleCode=" Rrule" valign="top">15 </td><td align="center" styleCode=" Rrule" valign="top">5 </td><td align="center" styleCode=" Rrule" valign="top">16 </td><td align="center" styleCode=" Rrule" valign="top">5 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Dizziness </td><td align="center" styleCode=" Rrule" valign="top">6 </td><td align="center" styleCode=" Rrule" valign="top">5 </td><td align="center" styleCode=" Rrule" valign="top">6 </td><td align="center" styleCode=" Rrule" valign="top">5 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Tremor </td><td align="center" styleCode=" Rrule" valign="top">5 </td><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">4 </td><td align="center" styleCode=" Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Nervousness </td><td align="center" styleCode=" Rrule" valign="top">4 </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Libido Decreased </td><td align="center" styleCode=" Rrule" valign="top">9 </td><td align="center" styleCode=" Rrule" valign="top">2 </td><td align="center" styleCode=" Rrule" valign="top">5 </td><td align="center" styleCode=" Rrule" valign="top">2 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Abnormal Dreams </td><td styleCode=" Botrule Rrule" valign="top"/><td styleCode=" Botrule Rrule" valign="top"/><td align="center" styleCode=" Botrule Rrule" valign="top">3 </td><td styleCode=" Botrule Rrule" valign="top"/></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Respiratory</content> <content styleCode="bold">System</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Respiratory Disorder </td><td align="center" styleCode=" Rrule" valign="top">7 </td><td align="center" styleCode=" Rrule" valign="top">5 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td></tr><tr><td align="left" style

de=" Lrule Rrule" valign="top">Respiratory Disorder </td><td align="center" styleCode=" Rrule" valign="top">7 </td><td align="center" styleCode=" Rrule" valign="top">5 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td></tr><tr><td align="left" style Code=" Lrule Rrule" valign="top">Sinusitis </td><td align="center" styleCode=" Rrule" valign="top">4 </td><td align="center" styleCode=" Rrule" valign="top">3 </td><td align="center" styleCode=" Rrule" valign="top">- </td><td align="center" styleCode=" Rrule" valign="top">- </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Yawn </td><td align="center" styleCode=" Botrule Rrule" valign="top">4 </td><td align="center" styleCode=" Botrule Rrule" valign="top">- </td><td align="center" styleCode=" Botrule Rrule" valign="top">2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">&lt; 1 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Special Senses</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Abnormal Vision </td><td align="center" styleCode=" Botrule Rrule" valign="top">2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td><td align="center" styleCode=" Botrule Rrule" valign="top">3 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">Urogenital</content> <content styleCode="bold">System</content> </td><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/><td styleCode=" Rrule" valign="top"/></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Abnormal Ejaculation ^a </td><td align="center" styleCode=" Rrule" valign="top">25 </td><td align="center" styleCode=" Rrule" valign="top">2 </td><td align="center" styleCode=" Rrule" valign="top">13 </td><td align="center" styleCode=" Rrule" valign="top">2 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top">Female Genital Disorder ^a </td><td align="center" styleCode=" Rrule" valign="top">4 </td><td align="center" styleCode=" Rrule" valign="top">1 </td><td align="center" styleCode=" Rrule" valign="top">5 </td><td align="center" styleCode=" Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Impotence ^a </td><td align="center" styleCode=" Botrule Rrule" valign="top">4 </td><td align="center" styleCode=" Botrule Rrule" valign="top">3 </td><td align="center" styleCode=" Botrule Rrule" valign="top">9 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td></tr></tbody></table>

="top">Impotence ^a </td><td align="center" styleCode=" Botrule Rrule" valign="top">4 </td><td align="center" styleCode=" Botrule Rrule" valign="top">3 </td><td align="center" styleCode=" Botrule Rrule" valign="top">9 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td></tr></tbody></table> <table ID="ID663" width="0" styleCode="Noautorules"><caption>Table 7 Adverse Reactions (&#x2265; 5% of Paroxetine-Treated Patients and &#x2265; Twice the Rate of Placebo) (in a Dose-Comparison Trial in the Treatment of MDD)</caption><col width="211"/><col width="84"/><col width="72"/><col width="72"/><col width="84"/><col width="73"/><tbody><tr><td rowspan="2" align="left" styleCode="Lrule Toprule Rrule" valign="top"><content styleCode="bold">Body System/Preferred Term</content> </td><td align="center" styleCode=" Toprule Rrule"><content styleCode="bold">Placebo</content> </td><td colspan="4" align="center" styleCode=" Toprule Botrule Rrule"><content styleCode="bold">Paroxetine</content> </td></tr><tr><td align="center" styleCode=" Rrule" valign="top"> <content styleCode="bold">n=51</content> </td><td align="center" styleCode=" Rrule"><content styleCode="bold">10 mg</content> <content styleCode="bold">n=102</content> </td><td align="center" styleCode=" Toprule Rrule"><content styleCode="bold">20 mg</content> <content styleCode="bold">n=104</content> </td><td align="center" styleCode=" Toprule Rrule"><content styleCode="bold">30 mg</content> <content styleCode="bold">n=101</content> </td><td align="center" styleCode=" Toprule Rrule"><content styleCode="bold">40 mg</content> <content styleCode="bold">n=102</content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule"> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule"><content styleCode="bold">%</content> </td></tr><tr><td align="left" styleCode=" Lrule Rrule"><content styleCode="bold">Body as a Whole</content> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule">Asthenia </td><td align="center" styleCode=" Botrule Rrule">0 </td><td align="center" styleCode=" Botrule Rrule">2.9 </td><td align="center" styleCode=" Botrule Rrule">10.6 </td><td align="center" styleCode=" Botrule Rrule">13.9 </td><td align="center" styleCode=" Botrule Rrule">12.7 </td></tr><tr><td align="left" styleCode=" Lrule Rrule"><content styleCode="bold">Dermatology</content> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule">Sweating </td><td align="center" styleCode=" Botrule Rrule">2 </td><td align="center" styleCode=" Botrule Rrule">1 </td><td align="center" styleCode=" Botrule Rrule">6.7 </td><td align="center" styleCode=" Botrule Rrule">8.9 </td><td align="center" styleCode=" Botrule Rrule">11.8 </td></tr><tr><td align="left" styleCode=" Lrule Rrule"><content styleCode="bold">Gastrointestinal</content> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td><td alig

" Botrule Rrule">11.8 </td></tr><tr><td align="left" styleCode=" Lrule Rrule"><content styleCode="bold">Gastrointestinal</content> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td><td alig n="center" styleCode=" Rrule"> </td></tr><tr><td align="left" styleCode=" Lrule Rrule">Constipation </td><td align="center" styleCode=" Rrule">5.9 </td><td align="center" styleCode=" Rrule">4.9 </td><td align="center" styleCode=" Rrule">7.7 </td><td align="center" styleCode=" Rrule">9.9 </td><td align="center" styleCode=" Rrule">12.7 </td></tr><tr><td align="left" styleCode=" Lrule Rrule">Decreased Appetite </td><td align="center" styleCode=" Rrule">2 </td><td align="center" styleCode=" Rrule">2 </td><td align="center" styleCode=" Rrule">5.8 </td><td align="center" styleCode=" Rrule">4 </td><td align="center" styleCode=" Rrule">4.9 </td></tr><tr><td align="left" styleCode=" Lrule Rrule">Diarrhea </td><td align="center" styleCode=" Rrule">7.8 </td><td align="center" styleCode=" Rrule">9.8 </td><td align="center" styleCode=" Rrule">19.2 </td><td align="center" styleCode=" Rrule">7.9 </td><td align="center" styleCode=" Rrule">14.7 </td></tr><tr><td align="left" styleCode=" Lrule Rrule">Dry Mouth </td><td align="center" styleCode=" Rrule">2 </td><td align="center" styleCode=" Rrule">10.8 </td><td align="center" styleCode=" Rrule">18.3 </td><td align="center" styleCode=" Rrule">15.8 </td><td align="center" styleCode=" Rrule">20.6 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule">Nausea </td><td align="center" styleCode=" Botrule Rrule">13.7 </td><td align="center" styleCode=" Botrule Rrule">14.7 </td><td align="center" styleCode=" Botrule Rrule">26.9 </td><td align="center" styleCode=" Botrule Rrule">34.7 </td><td align="center" styleCode=" Botrule Rrule">36.3 </td></tr><tr><td align="left" styleCode=" Lrule Rrule"><content styleCode="bold">Nervous System</content> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td></tr><tr><td align="left" styleCode=" Lrule Rrule">Anxiety </td><td align="center" styleCode=" Rrule">0 </td><td align="center" styleCode=" Rrule">2 </td><td align="center" styleCode=" Rrule">5.8 </td><td align="center" styleCode=" Rrule">5.9 </td><td align="center" styleCode=" Rrule">5.9 </td></tr><tr><td align="left" styleCode=" Lrule Rrule">Dizziness </td><td align="center" styleCode=" Rrule">3.9 </td><td align="center" styleCode=" Rrule">6.9 </td><td align="center" styleCode=" Rrule">6.7 </td><td align="center" styleCode=" Rrule">8.9 </td><td align="center" styleCode=" Rrule">12.7 </td></tr><tr><td align="left" styleCode=" Lrule Rrule">Nervousness </td><td align="center" styleCode=" Rrule">0 </td><td align="center" styleCode=" Rrule">5.9 </td><td align="center" styleCode=" Rrule">5.8 </td><td align="center" styleCode=" Rrule">4 </td><td align="center" styleCode=" Rrule">2.9 </td></tr><tr><td align="left" styleCode=" Lrule Rrule">Paresthesia </td><td align="center" styleCode=" Rrule">0 </td><td align="center" styleCode=" Rrule">2.9 </td><td align="center" styleCode=" Rrule">1 </td><td align="center" styleCode=" Rrule">5 </td><td align="center" styleCode=" Rrule">5.9 </td></tr><tr><td align="left" styleCode=" Lrule Rrule">Somnolence </td><td align="center" styleCode=" Rrule">7.8 </td><td align="center" styleCode=" Rrule">12.7 </td><td align="center" styleCode=" Rrule">18.3 </td><td align="center" styleCode=" Rrule">20.8 </td><td align="center" styleCode=" Rrule">21.6 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule">Tremor </td><td

e </td><td align="center" styleCode=" Rrule">7.8 </td><td align="center" styleCode=" Rrule">12.7 </td><td align="center" styleCode=" Rrule">18.3 </td><td align="center" styleCode=" Rrule">20.8 </td><td align="center" styleCode=" Rrule">21.6 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule">Tremor </td><td align="center" styleCode=" Botrule Rrule">0 </td><td align="center" styleCode=" Botrule Rrule">0 </td><td align="center" styleCode=" Botrule Rrule">7.7 </td><td align="center" styleCode=" Botrule Rrule">7.9 </td><td align="center" styleCode=" Botrule Rrule">14.7 </td></tr><tr><td align="left" styleCode=" Lrule Rrule"><content styleCode="bold">Special Senses</content> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule">Blurred Vision </td><td align="center" styleCode=" Botrule Rrule">2 </td><td align="center" styleCode=" Botrule Rrule">2.9 </td><td align="center" styleCode=" Botrule Rrule">2.9 </td><td align="center" styleCode=" Botrule Rrule">2 </td><td align="center" styleCode=" Botrule Rrule">7.8 </td></tr><tr><td align="left" styleCode=" Lrule Rrule"><content styleCode="bold">Urogenital System</content> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td><td align="center" styleCode=" Rrule"> </td></tr><tr><td align="left" styleCode=" Lrule Rrule">Abnormal Ejaculation </td><td align="center" styleCode=" Rrule">0 </td><td align="center" styleCode=" Rrule">5.8 </td><td align="center" styleCode=" Rrule">6.5 </td><td align="center" styleCode=" Rrule">10.6 </td><td align="center" styleCode=" Rrule">13 </td></tr><tr><td align="left" styleCode=" Lrule Rrule">Impotence </td><td align="center" styleCode=" Rrule">0 </td><td align="center" styleCode=" Rrule">1.9 </td><td align="center" styleCode=" Rrule">4.3 </td><td align="center" styleCode=" Rrule">6.4 </td><td align="center" styleCode=" Rrule">1.9 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule">Male Genital Disorders </td><td align="center" styleCode=" Botrule Rrule">0 </td><td align="center" styleCode=" Botrule Rrule">3.8 </td><td align="center" styleCode=" Botrule Rrule">8.7 </td><td align="center" styleCode=" Botrule Rrule">6.4 </td><td align="center" styleCode=" Botrule Rrule">3.7 </td></tr></tbody></table>

le Genital Disorders </td><td align="center" styleCode=" Botrule Rrule">0 </td><td align="center" styleCode=" Botrule Rrule">3.8 </td><td align="center" styleCode=" Botrule Rrule">8.7 </td><td align="center" styleCode=" Botrule Rrule">6.4 </td><td align="center" styleCode=" Botrule Rrule">3.7 </td></tr></tbody></table> <table ID="ID665" width="571" styleCode="Noautorules"><caption>Table 8 Adverse Reactions Related to Sexual Dysfunction in Patients Treated with Paroxetine in Clinical Trials of MDD, OCD, PD, SAD, GAD, and PTSD</caption><col width="294"/><col width="138"/><col width="139"/><tbody><tr><td align="left" styleCode="Lrule Toprule Botrule Rrule" valign="top"> </td><td align="center" styleCode=" Toprule Botrule Rrule" valign="top"><content styleCode="bold">Paroxetine</content> </td><td align="center" styleCode=" Toprule Botrule Rrule" valign="top"><content styleCode="bold">Placebo</content> </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">n (males)</content> </td><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">1,446</content> </td><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">1,042</content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Decreased Libido </td><td align="center" styleCode=" Botrule Rrule" valign="top">6 to15 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 to 5 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Ejaculatory Disturbance </td><td align="center" styleCode=" Botrule Rrule" valign="top">13 to 28 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 to 2 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Impotence </td><td align="center" styleCode=" Botrule Rrule" valign="top">2 to 9 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 to 3 </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">n (females)</content> </td><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">1,822</content> </td><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">1,340</content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Decreased Libido </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 to 9 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 to 2 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Orgasmic Disturbance </td><td align="center" styleCode=" Botrule Rrule" valign="top">2 to 9 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 to 1 </td></tr></tbody></table>

7 DRUG INTERACTIONS Table 9 presents clinically significant drug interactions with paroxetine. Table 9 Clinically Significant Drug Interactions with Paroxetine Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact The concomitant use of SSRIs, including paroxetine, and MAOIs increases the risk of serotonin syndrome. Intervention Paroxetine is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [see Dosage and Administration ( 2.5 ), Contraindications ( 4 ), Warnings and Precautions ( 5.2 )] . Examples selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue Pimozide and Thioridazine Clinical Impact Increased plasma concentrations of pimozide and thioridazine, drugs with a narrow therapeutic index, may increase the risk of QTc prolongation and ventricular arrhythmias. Intervention Paroxetine is contraindicated in patients taking pimozide or thioridazine [see Contraindications ( 4 )] . Other Serotonergic Drugs Clinical Impact The concomitant use of serotonergic drugs with paroxetine increases the risk of serotonin syndrome. Intervention Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of paroxetine and/or concomitant serotonergic drugs [see Warnings and Precautions ( 5.2 )] . Examples other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines and St. John's Wort. Drugs that Interfere with Hemostasis (antiplatelet agents and anticoagulants) Clinical Impact The concurrent use of an antiplatelet agent or anticoagulant with paroxetine may potentiate the risk of bleeding. Intervention Inform patients of the increased risk of bleeding associated with the concomitant use of paroxetine and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio [see Warnings and Precautions ( 5.5 )] . Examples aspirin, clopidogrel, heparin, warfarin Drugs Highly Bound to Plasma Protein Clinical Impact Paroxetine is highly bound to plasma protein. The concomitant use of paroxetine with another drug that is highly bound to plasma protein may increase free concentrations of paroxetine or other tightly-bound drugs in plasma. Intervention Monitor for adverse reactions and reduce dosage of paroxetine or other protein-bound drugs as warranted. Examples warfarin Drugs Metabolized by CYP2D6 Clinical Impact Paroxetine is a CYP2D6 inhibitor [see Clinical Pharmacology ( 12.3 )] . The concomitant use of paroxetine with a CYP2D6 substrate may increase the exposure of the CYP2D6 substrate. Intervention Decrease the dosage of a CYP2D6 substrate if needed with concomitant paroxetine use. Conversely, an increase in dosage of a CYP2D6 substrate may be needed if paroxetine is discontinued. Examples propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, venlafaxine, risperidone. Tamoxifen Clinical Impact Concomitant use of tamoxifen with paroxetine may lead to reduced plasma concentrations of the active metabolite (endoxifen) and reduced efficacy of tamoxifen Intervention Consider use of an alternative antidepressant with little or no CYP2D6 inhibition [see Warnings and Precautions ( 5.11 )] .

Tamoxifen Clinical Impact Concomitant use of tamoxifen with paroxetine may lead to reduced plasma concentrations of the active metabolite (endoxifen) and reduced efficacy of tamoxifen Intervention Consider use of an alternative antidepressant with little or no CYP2D6 inhibition [see Warnings and Precautions ( 5.11 )] . Fosamprenavir/Ritonavir Clinical Impact Co-administration of fosamprenavir/ritonavir with paroxetine significantly decreased plasma levels of paroxetine. Intervention Any dose adjustment should be guided by clinical effect (tolerability and efficacy). Drugs Highly Bound to Plasma Protein: Monitor for adverse reactions and reduce dosage of paroxetine or other protein-bound drugs (e.g., warfarin) as warranted. ( 7 ) Drugs Metabolized by CYP2D6: Reduce dosage of drugs metabolized by CYP2D6 as warranted. ( 7 ) Concomitant use with tamoxifen: Consider use of an alternative antidepressant with little or no CYP2D6 inhibition. ( 5.11 , 7 )

<table ID="ID747" width="590" styleCode="Noautorules"><caption>Table 9 Clinically Significant Drug Interactions with Paroxetine</caption><col width="121"/><col width="469"/><tbody><tr><td colspan="2" align="left" styleCode="Lrule Toprule Botrule Rrule" valign="top"><content styleCode="bold">Monoamine Oxidase Inhibitors (MAOIs)</content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="italics">Clinical Impact</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">The concomitant use of SSRIs, including paroxetine, and MAOIs increases the risk of serotonin syndrome. </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="italics">Intervention</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">Paroxetine is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue <content styleCode="italics">[see Dosage and Administration ( <linkHtml href="#ID599">2.5</linkHtml>), Contraindications ( <linkHtml href="#ID614">4</linkHtml>), Warnings and Precautions ( <linkHtml href="#ID624">5.2</linkHtml>)] </content>. </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="italics">Examples</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue </td></tr><tr><td colspan="2" align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Pimozide and Thioridazine</content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="italics">Clinical Impact</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">Increased plasma concentrations of pimozide and thioridazine, drugs with a narrow therapeutic index, may increase the risk of QTc prolongation and ventricular arrhythmias. </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="italics">Intervention</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">Paroxetine is contraindicated in patients taking pimozide or thioridazine <content styleCode="italics">[see Contraindications ( <linkHtml href="#ID614">4</linkHtml>)] </content>. </td></tr><tr><td colspan="2" align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Other Serotonergic Drugs</content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="italics">Clinical Impact</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">The concomitant use of serotonergic drugs with paroxetine increases the risk of serotonin syndrome. </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="italics">Intervention</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of paroxetine and/or concomitant serotonergic drugs <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID624">5.2</linkHtml>)] </content>.

and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of paroxetine and/or concomitant serotonergic drugs <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID624">5.2</linkHtml>)] </content>. </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="italics">Examples</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines and St. John&apos;s Wort. </td></tr><tr><td colspan="2" align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Drugs that Interfere with Hemostasis (antiplatelet agents and anticoagulants)</content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="italics">Clinical Impact</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">The concurrent use of an antiplatelet agent or anticoagulant with paroxetine may potentiate the risk of bleeding. </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="italics">Intervention</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">Inform patients of the increased risk of bleeding associated with the concomitant use of paroxetine and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID630">5.5</linkHtml>)] </content>. </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="italics">Examples</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">aspirin, clopidogrel, heparin, warfarin </td></tr><tr><td colspan="2" align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Drugs Highly Bound to Plasma Protein</content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="italics">Clinical Impact</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">Paroxetine is highly bound to plasma protein. The concomitant use of paroxetine with another drug that is highly bound to plasma protein may increase free concentrations of paroxetine or other tightly-bound drugs in plasma. </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="italics">Intervention</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">Monitor for adverse reactions and reduce dosage of paroxetine or other protein-bound drugs as warranted. </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="italics">Examples</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">warfarin </td></tr><tr><td colspan="2" align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Drugs Metabolized by CYP2D6</content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="italics">Clinical Impact</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">Paroxetine is a CYP2D6 inhibitor <content styleCode="italics">[see Clinical Pharmacology ( <linkHtml href="#ID702">12.3</linkHtml>)] </content>. The concomitant use of paroxetine with a CYP2D6 substrate may increase the exposure of the CYP2D6 substrate.

ent> </td><td align="left" styleCode=" Botrule Rrule" valign="top">Paroxetine is a CYP2D6 inhibitor <content styleCode="italics">[see Clinical Pharmacology ( <linkHtml href="#ID702">12.3</linkHtml>)] </content>. The concomitant use of paroxetine with a CYP2D6 substrate may increase the exposure of the CYP2D6 substrate. </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="italics">Intervention</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">Decrease the dosage of a CYP2D6 substrate if needed with concomitant paroxetine use. Conversely, an increase in dosage of a CYP2D6 substrate may be needed if paroxetine is discontinued. </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="italics">Examples</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, venlafaxine, risperidone. </td></tr><tr><td colspan="2" align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Tamoxifen</content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="italics">Clinical Impact</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">Concomitant use of tamoxifen with paroxetine may lead to reduced plasma concentrations of the active metabolite (endoxifen) and reduced efficacy of tamoxifen </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="italics">Intervention</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">Consider use of an alternative antidepressant with little or no CYP2D6 inhibition <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID642">5.11</linkHtml>)] </content>. </td></tr><tr><td colspan="2" align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Fosamprenavir/Ritonavir</content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="italics">Clinical Impact</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">Co-administration of fosamprenavir/ritonavir with paroxetine significantly decreased plasma levels of paroxetine. </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="italics">Intervention</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">Any dose adjustment should be guided by clinical effect (tolerability and efficacy). </td></tr></tbody></table>

8 USE IN SPECIFIC POPULATIONS Pregnancy: SSRI use, particularly later in pregnancy, may increase the risk for persistent pulmonary hypertension and symptoms of poor adaptation (respiratory distress, temperature instability, feeding difficulty, hypotonia, irritability) in the neonate. ( 8.1 ) 8.1 Pregnancy Risk Summary Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions ( 5.5 ) and Clinical Considerations]. Paroxetine is associated with a less than 2-fold increase in cardiovascular malformations when administered to a pregnant woman during the first trimester. While individual epidemiological studies on the association between paroxetine use and cardiac malformations have reported inconsistent findings, some meta-analyses of epidemiological studies have identified an increased risk of cardiovascular malformations (see Data). There are risks of persistent pulmonary hypertension of the newborn (PPHN) (see Data) and/or poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (SSRIs), including paroxetine during pregnancy. There also are risks associated with untreated depression in pregnancy (see Clinical Considerations). For women who intend to become pregnant or who are in their first trimester of pregnancy, paroxetine should be initiated only after consideration of the other available treatment options. No evidence of treatment related malformations was observed in animal reproduction studies, when paroxetine was administered during the period of organogenesis at doses up to 50 mg/kg/day in rats and 6 mg/kg/day in rabbits. These doses are approximately 8 (rat) and less than 2 (rabbit) times the maximum recommended human dose (MRHD – 60 mg) on an mg/m2 basis. When paroxetine was administered to female rats during the last trimester of gestation and continued through lactation, there was an increase in the number of pup deaths during the first four days of lactation. This effect occurred at a dose of 1 mg/kg/day which is less than the MRHD on an mg/m2 basis ( See Data ). The background risks of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryofetal risk Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants. This finding is from a prospective, longitudinal study of 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and the postpartum. Maternal Adverse Reactions Use of paroxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions ( 5.5 )].

he risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and the postpartum. Maternal Adverse Reactions Use of paroxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions ( 5.5 )]. Fetal/Neonatal adverse reactions Neonates exposed to paroxetine and other SSRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremors, jitteriness, irritability and constant crying. These findings are consistent with either a direct toxic effect of SSRIs or possibly a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see Warnings and Precautions ( 5.2 )]. Data Human Data Published epidemiological studies on the association between first trimester paroxetine use and cardiovascular malformations have reported inconsistent results; however, meta-analyses of population-based cohort studies published between 1996 – 2017 indicate a less than 2-fold increased risk for overall cardiovascular malformations. Specific cardiac malformations identified in two meta-analyses include an approximately 2 to 2.5-fold increased risk for right ventricular outflow tract defects. One meta-analysis also identified an increased risk (less than 2-fold) for bulbus cordis anomalies and anomalies of cardiac septal closure, and an increased risk for atrial septal defect (pooled OR 2.38, 95% CI 1.14-4.97). Important limitations of the studies included in these meta-analyses include potential confounding by indication, depression severity and potential exposure misclassification. Exposure to SSRIs, particularly later in pregnancy, may have an increased risk for PPHN. PPHN occurs in 1-2 per 1000 live births in the general population and is associated with substantial neonatal morbidity and mortality. Animal Data Reproduction studies were performed at doses up to 50 mg/kg/day in rats and 6 mg/kg/day in rabbits administered during organogenesis. These doses are approximately 8 (rat) and less than 2 (rabbit) times the maximum recommended human dose (MRHD 60 mg) on an mg/m2 basis. These studies have revealed no evidence of developmental effects. However, in rats, there was an increase in pup deaths during the first 4 days of lactation when dosing occurred during the last trimester of gestation and continued throughout lactation. This effect occurred at a dose of 1 mg/kg/day which is less than the MRHD on an mg/m2 basis. The no-effect dose for rat pup mortality was not determined. The cause of these deaths is not known. 8.2 Lactation Risk Summary Data from the published literature report the presence of paroxetine in human milk (see Data). There are reports of agitation, irritability, poor feeding and poor weight gain in infants exposed to paroxetine through breast milk (see Clinical Considerations ). There are no data on the effect of paroxetine on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Paxil and any potential adverse effects on the breastfed child from paroxetine or from underlying maternal condition. Clinical Considerations Infants exposed to paroxetine should be monitored for agitation, irritability, poor feeding and poor weight gain.

g should be considered along with the mother's clinical need for Paxil and any potential adverse effects on the breastfed child from paroxetine or from underlying maternal condition. Clinical Considerations Infants exposed to paroxetine should be monitored for agitation, irritability, poor feeding and poor weight gain. Data Published literature suggests the presence of paroxetine in human milk with relative infant doses ranging between 0.4% to 2.2%, and a milk/plasma ratio of <1. No significant amounts were detected in the plasma of infants after breastfeeding. 8.3 Females and Males of Reproductive Potential Infertility Male Based on findings from clinical studies, paroxetine may affect sperm quality which may impair fertility; it is not known if this effect is reversible [see Nonclinical Toxicology ( 13.1 )]. 8.4 Pediatric Use The safety and effectiveness of paroxetine in pediatric patients have not been established [see Box Warning]. Effectiveness was not demonstrated in three placebo-controlled trials in 752 paroxetine-treated pediatric patients with MDD. Antidepressants increase the risk of suicidal thoughts and behaviors in pediatric patients [see Boxed Warning , Warnings and Precautions ( 5.1 )]. Decreased appetite and weight loss have been observed in association with the use of SSRIs. In placebo-controlled clinical trials conducted with pediatric patients, the following adverse reactions were reported in at least 2% of pediatric patients treated with paroxetine and occurred at a rate at least twice that for pediatric patients receiving placebo: emotional lability (including self- harm, suicidal thoughts, attempted suicide, crying, and mood fluctuations), hostility, decreased appetite, tremor, sweating, hyperkinesia, and agitation. Adverse reactions upon discontinuation of treatment with paroxetine in the pediatric clinical trials that included a taper phase regimen, which occurred in at least 2% of patients and at a rate at least twice that of placebo, were: emotional lability (including suicidal ideation, suicide attempt, mood changes, and tearfulness), nervousness, dizziness, nausea, and abdominal pain. 8.5 Geriatric Use In premarketing clinical trials with paroxetine, 17% of patients treated with paroxetine (approximately 700) were 65 years of age or older. Pharmacokinetic studies revealed a decreased clearance in the elderly, and a lower starting dose is recommended; however, no overall differences in safety or effectiveness were observed between elderly and younger patients [see Dosage and Administration ( 2.4 ), Clinical Pharmacology ( 12.3 )]. SSRIs including paroxetine, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [see Warnings and Precautions ( 5.7 )]. 8.6 Renal and Hepatic Impairment Increased plasma concentrations of paroxetine occur in patients with renal and hepatic impairment. The initial dosage of paroxetine should be reduced in patients with severe renal impairment and in patients with severe hepatic impairment [see Dosage and Administration ( 2.4 ), Clinical Pharmacology ( 12.3 )].

8.1 Pregnancy Risk Summary Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions ( 5.5 ) and Clinical Considerations]. Paroxetine is associated with a less than 2-fold increase in cardiovascular malformations when administered to a pregnant woman during the first trimester. While individual epidemiological studies on the association between paroxetine use and cardiac malformations have reported inconsistent findings, some meta-analyses of epidemiological studies have identified an increased risk of cardiovascular malformations (see Data). There are risks of persistent pulmonary hypertension of the newborn (PPHN) (see Data) and/or poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (SSRIs), including paroxetine during pregnancy. There also are risks associated with untreated depression in pregnancy (see Clinical Considerations). For women who intend to become pregnant or who are in their first trimester of pregnancy, paroxetine should be initiated only after consideration of the other available treatment options. No evidence of treatment related malformations was observed in animal reproduction studies, when paroxetine was administered during the period of organogenesis at doses up to 50 mg/kg/day in rats and 6 mg/kg/day in rabbits. These doses are approximately 8 (rat) and less than 2 (rabbit) times the maximum recommended human dose (MRHD – 60 mg) on an mg/m2 basis. When paroxetine was administered to female rats during the last trimester of gestation and continued through lactation, there was an increase in the number of pup deaths during the first four days of lactation. This effect occurred at a dose of 1 mg/kg/day which is less than the MRHD on an mg/m2 basis ( See Data ). The background risks of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryofetal risk Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants. This finding is from a prospective, longitudinal study of 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and the postpartum. Maternal Adverse Reactions Use of paroxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions ( 5.5 )]. Fetal/Neonatal adverse reactions Neonates exposed to paroxetine and other SSRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support and tube feeding. Such complications can arise immediately upon delivery.

m hemorrhage [see Warnings and Precautions ( 5.5 )]. Fetal/Neonatal adverse reactions Neonates exposed to paroxetine and other SSRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremors, jitteriness, irritability and constant crying. These findings are consistent with either a direct toxic effect of SSRIs or possibly a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see Warnings and Precautions ( 5.2 )]. Data Human Data Published epidemiological studies on the association between first trimester paroxetine use and cardiovascular malformations have reported inconsistent results; however, meta-analyses of population-based cohort studies published between 1996 – 2017 indicate a less than 2-fold increased risk for overall cardiovascular malformations. Specific cardiac malformations identified in two meta-analyses include an approximately 2 to 2.5-fold increased risk for right ventricular outflow tract defects. One meta-analysis also identified an increased risk (less than 2-fold) for bulbus cordis anomalies and anomalies of cardiac septal closure, and an increased risk for atrial septal defect (pooled OR 2.38, 95% CI 1.14-4.97). Important limitations of the studies included in these meta-analyses include potential confounding by indication, depression severity and potential exposure misclassification. Exposure to SSRIs, particularly later in pregnancy, may have an increased risk for PPHN. PPHN occurs in 1-2 per 1000 live births in the general population and is associated with substantial neonatal morbidity and mortality. Animal Data Reproduction studies were performed at doses up to 50 mg/kg/day in rats and 6 mg/kg/day in rabbits administered during organogenesis. These doses are approximately 8 (rat) and less than 2 (rabbit) times the maximum recommended human dose (MRHD 60 mg) on an mg/m2 basis. These studies have revealed no evidence of developmental effects. However, in rats, there was an increase in pup deaths during the first 4 days of lactation when dosing occurred during the last trimester of gestation and continued throughout lactation. This effect occurred at a dose of 1 mg/kg/day which is less than the MRHD on an mg/m2 basis. The no-effect dose for rat pup mortality was not determined. The cause of these deaths is not known.

8.4 Pediatric Use The safety and effectiveness of paroxetine in pediatric patients have not been established [see Box Warning]. Effectiveness was not demonstrated in three placebo-controlled trials in 752 paroxetine-treated pediatric patients with MDD. Antidepressants increase the risk of suicidal thoughts and behaviors in pediatric patients [see Boxed Warning , Warnings and Precautions ( 5.1 )]. Decreased appetite and weight loss have been observed in association with the use of SSRIs. In placebo-controlled clinical trials conducted with pediatric patients, the following adverse reactions were reported in at least 2% of pediatric patients treated with paroxetine and occurred at a rate at least twice that for pediatric patients receiving placebo: emotional lability (including self- harm, suicidal thoughts, attempted suicide, crying, and mood fluctuations), hostility, decreased appetite, tremor, sweating, hyperkinesia, and agitation. Adverse reactions upon discontinuation of treatment with paroxetine in the pediatric clinical trials that included a taper phase regimen, which occurred in at least 2% of patients and at a rate at least twice that of placebo, were: emotional lability (including suicidal ideation, suicide attempt, mood changes, and tearfulness), nervousness, dizziness, nausea, and abdominal pain.

8.5 Geriatric Use In premarketing clinical trials with paroxetine, 17% of patients treated with paroxetine (approximately 700) were 65 years of age or older. Pharmacokinetic studies revealed a decreased clearance in the elderly, and a lower starting dose is recommended; however, no overall differences in safety or effectiveness were observed between elderly and younger patients [see Dosage and Administration ( 2.4 ), Clinical Pharmacology ( 12.3 )]. SSRIs including paroxetine, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [see Warnings and Precautions ( 5.7 )].

11 DESCRIPTION Paroxetine tablets, USP contains paroxetine hydrochloride, an SSRI. It is the hydrochloride salt of a phenylpiperidine compound identified chemically as (-)- trans -4 R -(4'-fluorophenyl)-3 S -[(3',4'- methylenedioxyphenoxy) methyl] piperidine hydrochloride hemihydrate and has the molecular formula of C 19 H 20 FNO 3 •HCl•1/2H 2 O. The molecular weight is 374.8 (329.4 as free base). The structural formula of paroxetine hydrochloride is: Paroxetine hydrochloride, USP is an odorless, white to off-white crystalline powder, having a melting point range of 120°C to 138°C. It is freely soluble in methanol, soluble in ethanol, sparingly soluble in dichloromethane and slightly soluble in water. Paroxetine tablets are for oral administration. Each film-coated tablet contains 10 mg, 20 mg, 30 mg, or 40 mg of paroxetine equivalent to 11.1 mg, 22.2 mg, 33.3 mg or 44.4 mg of paroxetine hydrochloride, respectively. In addition, each tablet contains the following inactive ingredients: dibasic calcium phosphate anhydrous, hypromellose 6 cP, lactose anhydrous, magnesium stearate, polyethylene glycol 6000, povidone, sodium starch glycolate, talc, and titanium dioxide. Image

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The mechanism of action of paroxetine in the treatment of MDD, SAD, OCD, PD, GAD, and PTSD is unknown, but is presumed to be linked to potentiation of serotonergic activity in the central nervous system resulting from inhibition of neuronal reuptake of serotonin (5-hydroxy-tryptamine, 5-HT). 12.2 Pharmacodynamics Studies at clinically relevant doses in humans have demonstrated that paroxetine blocks the uptake of serotonin into human platelets. In vitro studies in animals also suggest that paroxetine is a potent and highly selective inhibitor of neuronal serotonin reuptake (SSRI) and has only very weak effects on norepinephrine and dopamine neuronal reuptake. 12.3 Pharmacokinetics Nonlinearity in pharmacokinetics is observed with increasing doses of paroxetine. In a meta-analysis of paroxetine from 4 studies done in healthy volunteers following multiple dosing of 20 mg/day to 40 mg/day, males did not exhibit a significantly lower C max or AUC than females. Absorption Paroxetine hydrochloride is completely absorbed after oral dosing of a solution of the hydrochloride salt. In a study in which normal male subjects (n = 15) received 30 mg tablets daily for 30 days, steady-state paroxetine concentrations were achieved by approximately 10 days for most subjects, although it may take substantially longer in an occasional patient. At steady state, mean values of C max , T max , C min , and T ½ were 61.7 ng/mL (CV 45%), 5.2 hr. (CV 10%), 30.7 ng/mL (CV 67%), and 21 hours (CV 32%), respectively. The steady-state C max and C min values were about 6 and 14 times what would be predicted from single-dose studies. Steady-state drug exposure based on AUC 0-24 was about 8 times greater than would have been predicted from single-dose data in these subjects. The excess accumulation is a consequence of the fact that 1 of the enzymes that metabolizes paroxetine is readily saturable. Paroxetine is equally bioavailable from the oral suspension and tablet. Effect of Food The effects of food on the bioavailability of paroxetine were studied in subjects administered a single dose with and without food. AUC was only slightly increased (6%) when drug was administered with food but the C max was 29% greater, while the time to reach peak plasma concentration decreased from 6.4 hours post-dosing to 4.9 hours. Distribution Paroxetine distributes throughout the body, including the CNS, with only 1% remaining in the plasma. Approximately 95% and 93% of paroxetine is bound to plasma protein at 100 ng/mL and 400 ng/mL, respectively. Under clinical conditions, paroxetine concentrations would normally be less than 400 ng/mL. Paroxetine does not alter the in vitro protein binding of phenytoin or warfarin. Elimination Metabolism The mean elimination half-life is approximately 21 hours (CV 32%) after oral dosing of 30 mg tablets daily for 30 days of paroxetine. In steady-state dose proportionality studies involving elderly and nonelderly patients, at doses of 20 mg to 40 mg daily for the elderly and 20 mg to 50 mg daily for the nonelderly, some nonlinearity was observed in both populations, again reflecting a saturable metabolic pathway. In comparison to C min values after 20 mg daily, values after 40 mg daily were only about 2 to 3 times greater than doubled. Paroxetine is extensively metabolized after oral administration.

0 mg daily for the nonelderly, some nonlinearity was observed in both populations, again reflecting a saturable metabolic pathway. In comparison to C min values after 20 mg daily, values after 40 mg daily were only about 2 to 3 times greater than doubled. Paroxetine is extensively metabolized after oral administration. The principal metabolites are polar and conjugated products of oxidation and methylation, which are readily cleared. Conjugates with glucuronic acid and sulfate predominate, and major metabolites have been isolated and identified. Data indicate that the metabolites have no more than 1/50 the potency of the parent compound at inhibiting serotonin uptake. The metabolism of paroxetine is accomplished in part by CYP2D6. Saturation of this enzyme at clinical doses appears to account for the nonlinearity of paroxetine kinetics with increasing dose and increasing duration of treatment. The role of this enzyme in paroxetine metabolism also suggests potential drug-drug interactions [see Drug Interactions ( 7 )]. Pharmacokinetic behavior of paroxetine has not been evaluated in subjects who are deficient in CYP2D6 (poor metabolizers). Excretion Approximately 64% of a 30-mg oral solution dose of paroxetine was excreted in the urine with 2% as the parent compound and 62% as metabolites over a 10-day post-dosing period. About 36% was excreted in the feces (probably via the bile), mostly as metabolites and less than 1% as the parent compound over the 10-day post-dosing period. Drug Interaction Studies There are clinically significant, known drug interactions between paroxetine and other drugs [see Drug Interactions ( 7 )]. Figure 1 Impact of Paroxetine on the Pharmacokinetics of Co-Administered Drugs (log scale) Figure 2 Impact of Co-Administered Drugs on the Pharmacokinetics of Paroxetine Theophylline: Reports of elevated theophylline levels associated with paroxetine treatment have been reported. While this interaction has not been formally studied, it is recommended that theophylline levels be monitored when these drugs are concurrently administered. Drugs Metabolized by Cytochrome CYP3A4 An in vivo interaction study involving the co-administration under steady-state conditions of paroxetine and terfenadine, a substrate for CYP3A4, revealed no effect of paroxetine on terfenadine pharmacokinetics. In addition, in vitro studies have shown ketoconazole, a potent inhibitor of CYP3A4 activity, to be at least 100 times more potent than paroxetine as an inhibitor of the metabolism of several substrates for this enzyme, including terfenadine, triazolam and cyclosporine. Paroxetine's extent of inhibition of CYP3A4 activity is not expected to be of clinical significance. Specific Populations The impact of specific populations on the pharmacokinetics of paroxetine are shown in Figure 3. The recommended starting dosage and maximum dosage of paroxetine is reduced in elderly patients, patients with severe renal impairment, and patients with severe hepatic impairment [see Dosage and Administration ( 2.4 )]. Figure 3 Impact of Specific Population on the Pharmacokinetics of Paroxetine (log scale) Image Image Image

12.1 Mechanism of Action The mechanism of action of paroxetine in the treatment of MDD, SAD, OCD, PD, GAD, and PTSD is unknown, but is presumed to be linked to potentiation of serotonergic activity in the central nervous system resulting from inhibition of neuronal reuptake of serotonin (5-hydroxy-tryptamine, 5-HT).

12.3 Pharmacokinetics Nonlinearity in pharmacokinetics is observed with increasing doses of paroxetine. In a meta-analysis of paroxetine from 4 studies done in healthy volunteers following multiple dosing of 20 mg/day to 40 mg/day, males did not exhibit a significantly lower C max or AUC than females. Absorption Paroxetine hydrochloride is completely absorbed after oral dosing of a solution of the hydrochloride salt. In a study in which normal male subjects (n = 15) received 30 mg tablets daily for 30 days, steady-state paroxetine concentrations were achieved by approximately 10 days for most subjects, although it may take substantially longer in an occasional patient. At steady state, mean values of C max , T max , C min , and T ½ were 61.7 ng/mL (CV 45%), 5.2 hr. (CV 10%), 30.7 ng/mL (CV 67%), and 21 hours (CV 32%), respectively. The steady-state C max and C min values were about 6 and 14 times what would be predicted from single-dose studies. Steady-state drug exposure based on AUC 0-24 was about 8 times greater than would have been predicted from single-dose data in these subjects. The excess accumulation is a consequence of the fact that 1 of the enzymes that metabolizes paroxetine is readily saturable. Paroxetine is equally bioavailable from the oral suspension and tablet. Effect of Food The effects of food on the bioavailability of paroxetine were studied in subjects administered a single dose with and without food. AUC was only slightly increased (6%) when drug was administered with food but the C max was 29% greater, while the time to reach peak plasma concentration decreased from 6.4 hours post-dosing to 4.9 hours. Distribution Paroxetine distributes throughout the body, including the CNS, with only 1% remaining in the plasma. Approximately 95% and 93% of paroxetine is bound to plasma protein at 100 ng/mL and 400 ng/mL, respectively. Under clinical conditions, paroxetine concentrations would normally be less than 400 ng/mL. Paroxetine does not alter the in vitro protein binding of phenytoin or warfarin. Elimination Metabolism The mean elimination half-life is approximately 21 hours (CV 32%) after oral dosing of 30 mg tablets daily for 30 days of paroxetine. In steady-state dose proportionality studies involving elderly and nonelderly patients, at doses of 20 mg to 40 mg daily for the elderly and 20 mg to 50 mg daily for the nonelderly, some nonlinearity was observed in both populations, again reflecting a saturable metabolic pathway. In comparison to C min values after 20 mg daily, values after 40 mg daily were only about 2 to 3 times greater than doubled. Paroxetine is extensively metabolized after oral administration. The principal metabolites are polar and conjugated products of oxidation and methylation, which are readily cleared. Conjugates with glucuronic acid and sulfate predominate, and major metabolites have been isolated and identified. Data indicate that the metabolites have no more than 1/50 the potency of the parent compound at inhibiting serotonin uptake. The metabolism of paroxetine is accomplished in part by CYP2D6. Saturation of this enzyme at clinical doses appears to account for the nonlinearity of paroxetine kinetics with increasing dose and increasing duration of treatment. The role of this enzyme in paroxetine metabolism also suggests potential drug-drug interactions [see Drug Interactions ( 7 )].

mplished in part by CYP2D6. Saturation of this enzyme at clinical doses appears to account for the nonlinearity of paroxetine kinetics with increasing dose and increasing duration of treatment. The role of this enzyme in paroxetine metabolism also suggests potential drug-drug interactions [see Drug Interactions ( 7 )]. Pharmacokinetic behavior of paroxetine has not been evaluated in subjects who are deficient in CYP2D6 (poor metabolizers). Excretion Approximately 64% of a 30-mg oral solution dose of paroxetine was excreted in the urine with 2% as the parent compound and 62% as metabolites over a 10-day post-dosing period. About 36% was excreted in the feces (probably via the bile), mostly as metabolites and less than 1% as the parent compound over the 10-day post-dosing period. Drug Interaction Studies There are clinically significant, known drug interactions between paroxetine and other drugs [see Drug Interactions ( 7 )]. Figure 1 Impact of Paroxetine on the Pharmacokinetics of Co-Administered Drugs (log scale) Figure 2 Impact of Co-Administered Drugs on the Pharmacokinetics of Paroxetine Theophylline: Reports of elevated theophylline levels associated with paroxetine treatment have been reported. While this interaction has not been formally studied, it is recommended that theophylline levels be monitored when these drugs are concurrently administered. Drugs Metabolized by Cytochrome CYP3A4 An in vivo interaction study involving the co-administration under steady-state conditions of paroxetine and terfenadine, a substrate for CYP3A4, revealed no effect of paroxetine on terfenadine pharmacokinetics. In addition, in vitro studies have shown ketoconazole, a potent inhibitor of CYP3A4 activity, to be at least 100 times more potent than paroxetine as an inhibitor of the metabolism of several substrates for this enzyme, including terfenadine, triazolam and cyclosporine. Paroxetine's extent of inhibition of CYP3A4 activity is not expected to be of clinical significance. Specific Populations The impact of specific populations on the pharmacokinetics of paroxetine are shown in Figure 3. The recommended starting dosage and maximum dosage of paroxetine is reduced in elderly patients, patients with severe renal impairment, and patients with severe hepatic impairment [see Dosage and Administration ( 2.4 )]. Figure 3 Impact of Specific Population on the Pharmacokinetics of Paroxetine (log scale) Image Image Image

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Two-year carcinogenicity studies were conducted in rodents given paroxetine in the diet at 1 mg/kg/day, 5 mg/kg/day, and 25 mg/kg/day (mice) and 1 mg/kg/day, 5 mg/kg/day, and 20 mg/kg/day (rats). These doses are up to 2 (mouse) and 3 (rat) times the MRHD of 60 mg on a mg/m 2 basis. There was a significantly greater number of male rats in the high-dose group with reticulum cell sarcomas (1/100, 0/50, 0/50, and 4/50 for control, low-, middle-, and high-dose groups, respectively) and a significantly increased linear trend across dose groups for the occurrence of lymphoreticular tumors in male rats. Female rats were not affected. Although there was a dose-related increase in the number of tumors in mice, there was no drug-related increase in the number of mice with tumors. The relevance of these findings to humans is unknown. Mutagenesis Paroxetine produced no genotoxic effects in a battery of 5 in vitro and 2 in vivo assays that included the following: Bacterial mutation assay, mouse lymphoma mutation assay, unscheduled DNA synthesis assay, and tests for cytogenetic aberrations in vivo in mouse bone marrow and in vitro in human lymphocytes and in a dominant lethal test in rats. Impairment of Fertility A reduced pregnancy rate was found in reproduction studies in rats at a dose of paroxetine of 15 mg/kg/day, which is 2 times the MRHD of 60 mg on a mg/m 2 basis. Irreversible lesions occurred in the reproductive tract of male rats after dosing in toxicity studies for 2 weeks to 52 weeks. These lesions consisted of vacuolation of epididymal tubular epithelium at 50 mg/kg/day and atrophic changes in the seminiferous tubules of the testes with arrested spermatogenesis at 25 mg/kg/day (8 and 4 times the MRHD of 60 mg on a mg/m 2 basis).

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Two-year carcinogenicity studies were conducted in rodents given paroxetine in the diet at 1 mg/kg/day, 5 mg/kg/day, and 25 mg/kg/day (mice) and 1 mg/kg/day, 5 mg/kg/day, and 20 mg/kg/day (rats). These doses are up to 2 (mouse) and 3 (rat) times the MRHD of 60 mg on a mg/m 2 basis. There was a significantly greater number of male rats in the high-dose group with reticulum cell sarcomas (1/100, 0/50, 0/50, and 4/50 for control, low-, middle-, and high-dose groups, respectively) and a significantly increased linear trend across dose groups for the occurrence of lymphoreticular tumors in male rats. Female rats were not affected. Although there was a dose-related increase in the number of tumors in mice, there was no drug-related increase in the number of mice with tumors. The relevance of these findings to humans is unknown. Mutagenesis Paroxetine produced no genotoxic effects in a battery of 5 in vitro and 2 in vivo assays that included the following: Bacterial mutation assay, mouse lymphoma mutation assay, unscheduled DNA synthesis assay, and tests for cytogenetic aberrations in vivo in mouse bone marrow and in vitro in human lymphocytes and in a dominant lethal test in rats. Impairment of Fertility A reduced pregnancy rate was found in reproduction studies in rats at a dose of paroxetine of 15 mg/kg/day, which is 2 times the MRHD of 60 mg on a mg/m 2 basis. Irreversible lesions occurred in the reproductive tract of male rats after dosing in toxicity studies for 2 weeks to 52 weeks. These lesions consisted of vacuolation of epididymal tubular epithelium at 50 mg/kg/day and atrophic changes in the seminiferous tubules of the testes with arrested spermatogenesis at 25 mg/kg/day (8 and 4 times the MRHD of 60 mg on a mg/m 2 basis).

<table ID="ID717" width="591" styleCode="Noautorules"><caption>Table 10 Outcome Classification (%) on CGI-Global Improvement Item for Completers in Study 1 in Patients with OCD</caption><col width="175"/><col width="108"/><col width="102"/><col width="97"/><col width="109"/><tbody><tr><td align="left" styleCode="Lrule Toprule Rrule" valign="top"><content styleCode="bold">Outcome</content> <content styleCode="bold">Classification</content> </td><td align="center" styleCode=" Toprule Rrule" valign="top"><content styleCode="bold">Placebo</content> </td><td align="center" styleCode=" Toprule Rrule" valign="top"><content styleCode="bold">Paroxetine 20 mg</content> </td><td align="center" styleCode=" Toprule Rrule" valign="top"><content styleCode="bold">Paroxetine 40 mg</content> </td><td align="center" styleCode=" Toprule Rrule" valign="top"><content styleCode="bold">Paroxetine 60 mg</content> </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"> </td><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">(n = 74)</content> </td><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">(n = 75)</content> </td><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">(n = 66)</content> </td><td align="center" styleCode=" Rrule" valign="top"><content styleCode="bold">(n = 66)</content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">%</content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Worse </td><td align="center" styleCode=" Botrule Rrule" valign="top">14 </td><td align="center" styleCode=" Botrule Rrule" valign="top">7 </td><td align="center" styleCode=" Botrule Rrule" valign="top">7 </td><td align="center" styleCode=" Botrule Rrule" valign="top">3 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">No Change </td><td align="center" styleCode=" Botrule Rrule" valign="top">44 </td><td align="center" styleCode=" Botrule Rrule" valign="top">35 </td><td align="center" styleCode=" Botrule Rrule" valign="top">22 </td><td align="center" styleCode=" Botrule Rrule" valign="top">19 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Minimally Improved </td><td align="center" styleCode=" Botrule Rrule" valign="top">24 </td><td align="center" styleCode=" Botrule Rrule" valign="top">33 </td><td align="center" styleCode=" Botrule Rrule" valign="top">29 </td><td align="center" styleCode=" Botrule Rrule" valign="top">34 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Much Improved </td><td align="center" styleCode=" Botrule Rrule" valign="top">11 </td><td align="center" styleCode=" Botrule Rrule" valign="top">18 </td><td align="center" styleCode=" Botrule Rrule" valign="top">22 </td><td align="center" styleCode=" Botrule Rrule" valign="top">24 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Very Much Improved </td><td align="center" styleCode=" Botrule Rrule" valign="top">7 </td><td align="center" styleCode=" Botrule Rrule" valig

de=" Botrule Rrule" valign="top">22 </td><td align="center" styleCode=" Botrule Rrule" valign="top">24 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Very Much Improved </td><td align="center" styleCode=" Botrule Rrule" valign="top">7 </td><td align="center" styleCode=" Botrule Rrule" valig n="top">7 </td><td align="center" styleCode=" Botrule Rrule" valign="top">20 </td><td align="center" styleCode=" Botrule Rrule" valign="top">20 </td></tr></tbody></table>

16 HOW SUPPLIED/STORAGE AND HANDLING Paroxetine Tablets USP, 20 mg are white to off-white, round-shaped, biconvex, film-coated tablets debossed with the logo of 'ZC, 16 and bisect' on one side and plain on other side, and are supplied as follows: NDC: 70518-3518-00 NDC: 70518-3518-01 NDC: 70518-3518-02 NDC: 70518-3518-03 NDC: 70518-3518-04 NDC: 70518-3518-06 PACKAGING: 100 in 1 BOTTLE PLASTIC PACKAGING: 30 in 1 BLISTER PACK PACKAGING: 100 in 1 BOX PACKAGING: 1 in 1 POUCH PACKAGING: 30 in 1 BOTTLE PLASTIC PACKAGING: 45 in 1 BOTTLE PLASTIC Store at 20°C to 25° C (68°F to 77° F) [See USP Controlled Room Temperature]. Repackaged and Distributed By: Remedy Repack, Inc. 625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Suicidal Thoughts and Behaviors Advise patients and caregivers to look for the emergence of suicidality, especially early during treatment and when the dosage is adjusted up or down, and instruct them to report such symptoms to the healthcare provider [see Boxed Warning and Warnings and Precautions ( 5.1 )]. Serotonin Syndrome Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of paroxetine with other serotonergic drugs including triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, St. John's Wort, and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid). Instruct patients to contact their health care provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome [see Warnings and Precautions ( 5.2 ), Drug Interactions ( 7 )]. Concomitant Medications Advise patients to inform their physician if they are taking, or plan to take, any prescription or over-the-counter drugs, since there is a potential for drug-drug interactions [see Warning and Precautions ( 5.3 ), Drug Interactions ( 7 )]. Increased Risk of Bleeding Inform patients about the concomitant use of paroxetine with aspirin, NSAIDs, other antiplatelet drugs, warfarin, or other anticoagulants because the combined use has been associated with an increased risk of bleeding. Advise patients to inform their health care providers if they are taking or planning to take any prescription or over-the counter medications that increase the risk of bleeding [see Warnings and Precautions ( 5.5 )]. Activation of Mania/Hypomania Advise patients and their caregivers to observe for signs of activation of mania/hypomania and instruct them to report such symptoms to the healthcare provider [see Warnings and Precautions ( 5.6 )]. Discontinuation Syndrome Advise patients not to abruptly discontinue paroxetine and to discuss any tapering regimen with their healthcare provider. Inform patients that adverse reactions can occur when paroxetine is discontinued [see Warnings and Precautions ( 5.7 )]. Sexual Dysfunction Advise patients that use of paroxetine may cause symptoms of sexual dysfunction in both male and female patients. Inform patients that they should discuss any changes in sexual function and potential management strategies with their healthcare provider [see Warnings and Precautions ( 5.13 )]. Allergic Reactions Advise patients to notify their healthcare provider if they develop an allergic reaction such as rash, hives, swelling, or difficulty breathing [see Adverse Reactions ( 6.1 , 6.2 )]. Embryo-Fetal Toxicity Advise women to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with paroxetine. Advise women of risks associated with first trimester use of paroxetine and that use later in pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, tube feeding and/or persistent pulmonary hypertension of the newborn (PPHN) [see Warnings and Precautions ( 5.4 ), Use in Specific Populations ( 8.1 )].

er use of paroxetine and that use later in pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, tube feeding and/or persistent pulmonary hypertension of the newborn (PPHN) [see Warnings and Precautions ( 5.4 ), Use in Specific Populations ( 8.1 )]. Advise women that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to paroxetine during pregnancy [see Warnings and Precautions ( 5.4 ), Use in Specific Populations ( 8.1 )]. Lactation Advise breastfeeding women using paroxetine to monitor infants for agitation, irritability, poor feeding and poor weight gain and to seek medical care if they notice these signs [see Use in Specific Populations ( 8.2 )]. Females and Males of Reproductive Potential Advise men that paroxetine may affect sperm quality, which may impair fertility; it is not known if this effect is reversible [see Use in Specific Populations ( 8.3 )]. Medication Guide available at www.zydususa.com/medguides or call 1-877-993-8779. Repackaged By / Distributed By: RemedyRepack Inc. 625 Kolter Drive, Indiana, PA 15701 (724) 465-8762

Medication Guide Paroxetine (pa rox' e teen) Tablets, USP What is the most important information I should know about paroxetine tablets? Paroxetine tablets can cause serious side effects, including: ● Increased risk of suicidal thoughts or actions. Paroxetine tablets and other antidepressant medicines may increase suicidal thoughts and actions in some people 24 years of age and younger, especially within the first few months of treatment or when the dose is changed. Paroxetine tablets are not for use in children. ○ Depression or other mental illnesses are the most important causes of suicidal thoughts and actions. How can I watch for and try to prevent suicidal thoughts and actions? ○ Pay close attention to any changes, especially sudden changes in mood, behavior, thoughts or feelings or if you develop suicidal thoughts or actions. This is very important when an antidepressant medicine is started or when the does is changed. ○ Call your healthcare provider right away to report new or sudden changes in mood, behavior, thoughts or feelings or if you develop suicidal thoughts or actions. ○ Keep all follow-up visits with your healthcare provider as scheduled. Call your healthcare provider between visits as needed, especially if you have concerns about symptoms. Call your healthcare provider or get emergency medical help right away if you have any of the following symptoms, especially if they are new, worse, or worry you: ○ attempts to commit suicide ○ acting on dangerous impulses ○ acting aggressive or violent ○ thoughts about suicide or dying ○ new or worse depression ○ new or worse anxiety or panic attacks ○ feeling agitated, restless, angry, or irritable ○ trouble sleeping ○ an increase in activity and talking more than what is normal for you ○ other unusual changes in behavior or mood What are paroxetine tablets? Paroxetine tablets are prescription medicine used in adults to treat: ● A certain type of depression called Major Depressive Disorder (MDD) ● Obsessive Compulsive Disorder (OCD) ● Panic Disorder (PD) ● Social Anxiety Disorder (SAD) ● Generalized Anxiety Disorder (GAD) ● Posttraumatic Stress Disorder (PTSD) Do not take paroxetine tablets if you: ● take a monoamine oxidase inhibitor (MAOI) ● have stopped taking an MAOI in the last 14 days ● are being treated with the antibiotic linezolid or the intravenous methylene blue ● are taking pimozide ● are taking thioridazine ● are allergic to paroxetine or any of the ingredients in paroxetine tablets. See the end of this Medication Guide for a complete list of ingredients in paroxetine tablets. Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI or one of these medicines, including the antibiotic linezolid or intravenous methylene blue. Do not start taking an MAOI for at least 14 days after you stop treatment with paroxetine tablets. Before taking paroxetine tablets, tell your healthcare provider about all your medical conditions, including if you: ● have heart problems ● have or had bleeding problems ● have, or have a family history of, bipolar disorder, mania or hypomania ● have or had seizures or convulsions ● have glaucoma (high pressure in the eye) ● have low sodium levels in your blood ● have bone problems ● have kidney or liver problems ● are pregnant or plan to become pregnant. Paroxetine tablets may harm your unborn baby.

a family history of, bipolar disorder, mania or hypomania ● have or had seizures or convulsions ● have glaucoma (high pressure in the eye) ● have low sodium levels in your blood ● have bone problems ● have kidney or liver problems ● are pregnant or plan to become pregnant. Paroxetine tablets may harm your unborn baby. o Taking paroxetine during your first trimester of pregnancy may cause your baby to be at an increased risk of having a heart problem (cardiac malformations) at birth. o Taking paroxetine during your third trimester of pregnancy may cause your baby to have breathing, temperature and feeding problems, low muscle tone and irritability after birth and may cause your baby to be at an increased risk of a serious lung problem at birth. Talk to your healthcare provider about the risk to your unborn baby if you take paroxetine during pregnancy. o Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with paroxetine. o There is a pregnancy registry for females who are exposed to paroxetine during pregnancy. The purpose of the registry is to collect information about the health of females exposed to paroxetine and their baby. If you become pregnant during treatment with paroxetine talk to your healthcare provider. ● are breastfeeding or plan to breastfeed. Paroxetine passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with paroxetine tablets. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Paroxetine tablets and some other medicines may affect each other causing possible serious side effects. Paroxetine tablets may affect the way other medicines work and other medicines may affect the way paroxetine tablet works. Especially tell your healthcare provider if you take: medicines used to treat migraine headaches called triptans tricyclic antidepressants lithium Tramadol, fentanyl, meperidine, methadone, or other opioids tryptophan buspirone amphetamines St. John's Wort medicines that can affect blood clotting such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin diuretics tamoxifen medicines used to treat mood, anxiety, psychotic, or thought disorders, including selective serotonin reuptake (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) Ask your healthcare provider if you are not sure if you are taking any of these medicines. Your healthcare provider can tell you if it is safe to take paroxetine tablets with your other medicines. Do not start or stop any other medicines during treatment with paroxetine tablets without talking to your healthcare provider first. Stopping paroxetine tablets suddenly may cause you to have serious side effects . See, "What are the possible side effects of paroxetine tablets?" Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine. How should I take paroxetine tablets? ● Take paroxetine tablets exactly as prescribed. Your healthcare provider may need to change the dose of paroxetine tablets until it is the right dose for you. ● Take paroxetine tablet 1 time each day in the morning. ● Paroxetine tablets may be taken with or without food. ● If you take too much paroxetine tablets, call your poison control center at 1-800-222-1222 or go to the nearest hospital emergency room right away. What are possible side effects of paroxetine tablets? Paroxetine tablets can cause serious side effects, including: ● See, "What is the most important information I should know about paroxetine tablets?" ● Serotonin syndrome.

ison control center at 1-800-222-1222 or go to the nearest hospital emergency room right away. What are possible side effects of paroxetine tablets? Paroxetine tablets can cause serious side effects, including: ● See, "What is the most important information I should know about paroxetine tablets?" ● Serotonin syndrome. A potentially life-threatening problem called serotonin syndrome can happen when you take paroxetine tablets with certain other medicines. See, "Who should not take paroxetine tablets?" Call your healthcare provider or go to the nearest hospital emergency room right away if you have any of the following signs and symptoms of serotonin syndrome: ○ agitation ○ sweating ○ seeing or hearing things that are not real (hallucinations) ○ flushing ○ confusion ○ high body temperature (hyperthermia) ○ coma ○ shaking (tremors), stiff muscles, or muscle twitching ○ fast heart beat ○ loss of coordination ○ changes in blood pressure ○ seizures ○ dizziness ○ nausea, vomiting, diarrhea ● Eye problems (angle-closure glaucoma). Paroxetine tablets may cause a type of eye problem called angle-closure glaucoma in people with certain other eye conditions. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are. Call your healthcare provider if you have eye pain, changes in your vision, or swelling or redness in or around the eye. ● Medicine interactions. Taking paroxetine tablets with certain other medicines including thioridazine and pimozide may increase the risk of developing a serious heart problem called QT prolongation. ● Seizures (convulsions). ● Manic episodes. Manic episodes may happen in people with bipolar disorder who take paroxetine tablets. Symptoms may include: ○ greatly increased energy ○ severe problems sleeping ○ racing thoughts ○ reckless behavior ○ unusually grand ideas ○ excessive happiness or irritability ○ talking more or faster than usual ● Discontinuation syndrome. Suddenly stopping paroxetine tablets may cause you to have serious side effects. Your healthcare provider may want to decrease your dose slowly. Symptoms may include: ○ nausea ○ electric shock feeling (paresthesia) ○ tiredness ○ sweating ○ tremor ○ problems sleeping ○ changes in your mood ○ anxiety ○ hypomania irritability and agitation ○ confusion ○ ringing in your ears (tinnitus) ○ dizziness ○ headache ○ seizures ● Low sodium levels in your blood (hyponatremia). Low sodium levels in your blood that may be serious and may cause death, can happen during treatment with paroxetine tablets. Elderly people and people who take certain medicines may be at a greater risk for developing low sodium levels in your blood. Signs and symptoms may include: ○ headache ○ difficulty concentrating ○ memory changes ○ confusion ○ weakness and unsteadiness on your feet which can lead to falls In more severe or more sudden cases, signs and symptoms include: ○ seeing or hearing things that are not real (hallucinations) ○ fainting ○ seizures ○ coma ○ stopping breathing (respiratory arrest) ● Abnormal bleeding. Taking paroxetine tablets with aspirin, NSAIDs, or blood thinners may increase this risk. Tell your healthcare provider about any unusual bleeding or bruising. ● Bone fractures. ● Sexual problems (dysfunction). Taking selective serotonin reuptake inhibitors (SSRIs), including paroxetine, may cause sexual problems.

ing. Taking paroxetine tablets with aspirin, NSAIDs, or blood thinners may increase this risk. Tell your healthcare provider about any unusual bleeding or bruising. ● Bone fractures. ● Sexual problems (dysfunction). Taking selective serotonin reuptake inhibitors (SSRIs), including paroxetine, may cause sexual problems. Symptoms in males may include: o Delayed ejaculation or inability to have an ejaculation o Decreased sex drive o Problems getting or keeping an erection Symptoms in females may include: o Decreased sex drive o Delayed orgasm or inability to have an orgasm Talk to your healthcare provider if you develop any changes in your sexual function or if you have any questions or concerns about sexual problems during treatment with paroxetine. There may be treatments your healthcare provider can suggest. The most common side effects of paroxetine tablets include: ○ male and female sexual function problems ○ weakness (asthenia) ○ constipation ○ decreased appetite ○ diarrhea ○ dizziness ○ dry mouth ○ infection ○ problems sleeping ○ nausea ○ nervousness ○ sleepiness ○ sweating ○ shaking (tremor) ○ yawning These are not all the possible side effects of paroxetine tablets. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store paroxetine tablets? Store paroxetine tablets between 68°F to 77°F (20°C to 25°C). Paroxetine tablets come in child-resistant bottle pack of 30's and 90's. Keep paroxetine tablets and all medicines out of the reach of children. General information about the safe and effective use of paroxetine tablets. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not take paroxetine tablets for a condition for which it was not prescribed. Do not give paroxetine tablets to other people, even if they have the same symptoms that you have. It may harm them. You may ask your healthcare provider or pharmacist for information about paroxetine tablets that is written for healthcare professionals. What are the ingredients in paroxetine tablets? Active ingredient: paroxetine hydrochloride, USP Inactive ingredients: dibasic calcium phosphate anhydrous, hypromellose 6 cP, lactose anhydrous, magnesium stearate, polyethylene glycol 6000, povidone, sodium starch glycolate, talc, and titanium dioxide. Medication Guide available at www.zydususa.com/medguides or call 1-877-993-8779. Repackaged and Distributed By: Remedy Repack, Inc. 625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762 Rev.: 01/25 This Medication Guide has been approved by the U.S. Food and Drug Administration. Repackaged By / Distributed By: RemedyRepack Inc. 625 Kolter Drive, Indiana, PA 15701 (724) 465-8762

<table width="638" ID="ID734" styleCode="Noautorules"><colgroup><col width="213"/><col width="106"/><col width="18"/><col width="88"/><col width="213"/></colgroup><tbody><tr><td align="center" colspan="5" styleCode="Lrule Toprule Botrule Rrule" valign="top"><content styleCode="bold">Medication Guide</content> <content styleCode="bold">Paroxetine (pa rox&apos; e teen) Tablets, USP</content></td></tr><tr><td align="left" colspan="5" styleCode="Lrule Rrule" valign="top"><content styleCode="bold">What is the most important information I should know about paroxetine tablets?</content> <content styleCode="bold">Paroxetine tablets can cause serious side effects, including:</content> <content styleCode="bold">&#x25CF; Increased risk of suicidal thoughts or actions.</content>Paroxetine tablets and other antidepressant medicines may increase suicidal thoughts and actions in some people 24 years of age and younger, especially within the <content styleCode="bold">first few months of treatment or when the dose is changed. Paroxetine tablets are not for use in children.</content> <content styleCode="bold"> &#x25CB; Depression or other mental illnesses are the most important causes of suicidal thoughts and actions.</content> <content styleCode="bold">How can I watch for and try to prevent suicidal thoughts and actions?</content> <content styleCode="bold">&#x25CB; </content>Pay close attention to any changes, especially sudden changes in mood, behavior, thoughts or feelings or if you develop suicidal thoughts or actions. This is very important when an antidepressant medicine is started or when the does is changed. <content styleCode="bold">&#x25CB; </content>Call your healthcare provider right away to report new or sudden changes in mood, behavior, thoughts or feelings or if you develop suicidal thoughts or actions. <content styleCode="bold">&#x25CB; </content>Keep all follow-up visits with your healthcare provider as scheduled. Call your healthcare provider between visits as needed, especially if you have concerns about symptoms.

udden changes in mood, behavior, thoughts or feelings or if you develop suicidal thoughts or actions. <content styleCode="bold">&#x25CB; </content>Keep all follow-up visits with your healthcare provider as scheduled. Call your healthcare provider between visits as needed, especially if you have concerns about symptoms. <content styleCode="bold">Call your healthcare provider or get emergency medical help right away if you have any of the following symptoms, especially if they are new, worse, or worry you:</content></td></tr><tr><td align="left" colspan="2" styleCode="Lrule" valign="top"><content styleCode="bold">&#x25CB; </content>attempts to commit suicide </td><td align="left" colspan="3" styleCode="Rrule" valign="top"><content styleCode="bold">&#x25CB; </content>acting on dangerous impulses </td></tr><tr><td align="left" colspan="2" styleCode="Lrule" valign="top"><content styleCode="bold">&#x25CB; </content>acting aggressive or violent </td><td align="left" colspan="3" styleCode="Rrule" valign="top"><content styleCode="bold">&#x25CB; </content>thoughts about suicide or dying </td></tr><tr><td align="left" colspan="2" styleCode="Lrule" valign="top"><content styleCode="bold">&#x25CB; </content>new or worse depression </td><td align="left" colspan="3" styleCode="Rrule" valign="top"><content styleCode="bold">&#x25CB; </content>new or worse anxiety or panic attacks </td></tr><tr><td align="left" colspan="2" styleCode="Lrule" valign="top"><content styleCode="bold">&#x25CB; </content>feeling agitated, restless, angry, or irritable </td><td align="left" colspan="3" styleCode="Rrule" valign="top"><content styleCode="bold">&#x25CB; </content>trouble sleeping </td></tr><tr><td align="left" colspan="2" styleCode="Lrule Botrule" valign="top"><content styleCode="bold">&#x25CB; </content>an increase in activity and talking more than what is normal for you </td><td align="left" colspan="3" styleCode="Botrule Rrule" valign="top"><content styleCode="bold">&#x25CB; </content>other unusual changes in behavior or mood </td></tr><tr><td align="left" colspan="5" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">What are paroxetine tablets?</content> Paroxetine tablets are prescription medicine used in adults to treat: &#x25CF; A certain type of depression called Major Depressive Disorder (MDD) &#x25CF; Obsessive Compulsive Disorder (OCD) &#x25CF; Panic Disorder (PD) &#x25CF; Social Anxiety Disorder (SAD) &#x25CF; Generalized Anxiety Disorder (GAD) &#x25CF; Posttraumatic Stress Disorder (PTSD) </td></tr><tr><td align="left" colspan="5" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Do not take paroxetine tablets if you:</content> &#x25CF; take a monoamine oxidase inhibitor (MAOI) &#x25CF; have stopped taking an MAOI in the last 14 days &#x25CF; are being treated with the antibiotic linezolid or the intravenous methylene blue &#x25CF; are taking pimozide &#x25CF; are taking thioridazine &#x25CF; are allergic to paroxetine or any of the ingredients in paroxetine tablets. See the end of this Medication Guide for a complete list of ingredients in paroxetine tablets. Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI or one of these medicines, including the antibiotic linezolid or intravenous methylene blue.

or any of the ingredients in paroxetine tablets. See the end of this Medication Guide for a complete list of ingredients in paroxetine tablets. Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI or one of these medicines, including the antibiotic linezolid or intravenous methylene blue. <content styleCode="bold">Do not start taking an MAOI for at least 14 days after you stop treatment with paroxetine tablets.</content></td></tr><tr><td align="left" colspan="5" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Before taking paroxetine tablets, tell your healthcare provider about all your medical conditions, including if you:</content> &#x25CF; have heart problems &#x25CF; have or had bleeding problems &#x25CF; have, or have a family history of, bipolar disorder, mania or hypomania &#x25CF; have or had seizures or convulsions &#x25CF; have glaucoma (high pressure in the eye) &#x25CF; have low sodium levels in your blood &#x25CF; have bone problems &#x25CF; have kidney or liver problems &#x25CF; are pregnant or plan to become pregnant. Paroxetine tablets may harm your unborn baby. o Taking paroxetine during your first trimester of pregnancy may cause your baby to be at an increased risk of having a heart problem (cardiac malformations) at birth. o Taking paroxetine during your third trimester of pregnancy may cause your baby to have breathing, temperature and feeding problems, low muscle tone and irritability after birth and may cause your baby to be at an increased risk of a serious lung problem at birth. Talk to your healthcare provider about the risk to your unborn baby if you take paroxetine during pregnancy. o Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with paroxetine. o There is a pregnancy registry for females who are exposed to paroxetine during pregnancy. The purpose of the registry is to collect information about the health of females exposed to paroxetine and their baby. If you become pregnant during treatment with paroxetine talk to your healthcare provider. &#x25CF; are breastfeeding or plan to breastfeed. Paroxetine passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with paroxetine tablets. <content styleCode="bold">Tell your healthcare provider about all the medicines you take,</content>including prescription and over-the-counter medicines, vitamins, and herbal supplements. Paroxetine tablets and some other medicines may affect each other causing possible serious side effects. Paroxetine tablets may affect the way other medicines work and other medicines may affect the way paroxetine tablet works. <content styleCode="bold">Especially tell your healthcare provider if you take:</content><list listType="unordered" styleCode="Disc"><item>medicines used to treat migraine headaches called triptans</item><item>tricyclic antidepressants</item><item>lithium</item><item>Tramadol, fentanyl, meperidine, methadone, or other opioids</item><item>tryptophan</item><item> buspirone</item><item>amphetamines</item><item>St. John&apos;s Wort</item><item>medicines that can affect blood clotting such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin</item><item>diuretics</item><item>tamoxifen</item><item>medicines used to treat mood, anxiety, psychotic, or thought disorders, including selective serotonin reuptake (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs)</item></list> Ask your healthcare provider if you are not sure if you are taking any of these medicines. Your healthcare provider can tell you if it is safe to take paroxetine tablets with your other medicines.

ders, including selective serotonin reuptake (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs)</item></list> Ask your healthcare provider if you are not sure if you are taking any of these medicines. Your healthcare provider can tell you if it is safe to take paroxetine tablets with your other medicines. Do not start or stop any other medicines during treatment with paroxetine tablets without talking to your healthcare provider first. Stopping paroxetine tablets suddenly may cause you to have serious side effects <content styleCode="bold">.</content>See, <content styleCode="bold">&quot;What are the possible side effects of paroxetine tablets?&quot;</content> Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine. </td></tr><tr><td align="left" colspan="5" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">How should I take paroxetine tablets?</content> &#x25CF; Take paroxetine tablets exactly as prescribed. Your healthcare provider may need to change the dose of paroxetine tablets until it is the right dose for you. &#x25CF; Take paroxetine tablet 1 time each day in the morning. &#x25CF; Paroxetine tablets may be taken with or without food. &#x25CF; If you take too much paroxetine tablets, call your poison control center at 1-800-222-1222 or go to the nearest hospital emergency room right away. </td></tr><tr><td align="left" colspan="5" styleCode="Lrule Rrule" valign="top"><content styleCode="bold">What are possible side effects of paroxetine tablets?</content> <content styleCode="bold">Paroxetine tablets can cause serious side effects, including:</content> &#x25CF; See, <content styleCode="bold">&quot;What is the most important information I should know about paroxetine tablets?&quot;</content> &#x25CF; <content styleCode="bold">Serotonin syndrome.</content>A potentially life-threatening problem called serotonin syndrome can happen when you take paroxetine tablets with certain other medicines.

styleCode="bold">&quot;What is the most important information I should know about paroxetine tablets?&quot;</content> &#x25CF; <content styleCode="bold">Serotonin syndrome.</content>A potentially life-threatening problem called serotonin syndrome can happen when you take paroxetine tablets with certain other medicines. See, &quot;Who should not take paroxetine tablets?&quot; <content styleCode="bold">Call your healthcare provider or go to the nearest hospital emergency room right away</content>if you have any of the following signs and symptoms of serotonin syndrome: </td></tr><tr><td align="left" colspan="2" styleCode="Lrule" valign="top">&#x25CB; agitation</td><td align="left" colspan="3" styleCode="Rrule" valign="top">&#x25CB; sweating</td></tr><tr><td align="left" colspan="2" styleCode="Lrule" valign="top">&#x25CB; seeing or hearing things that are not real (hallucinations)</td><td align="left" colspan="3" styleCode="Rrule" valign="top">&#x25CB; flushing</td></tr><tr><td align="left" colspan="2" styleCode="Lrule" valign="top">&#x25CB; confusion</td><td align="left" colspan="3" styleCode="Rrule" valign="top">&#x25CB; high body temperature (hyperthermia)</td></tr><tr><td align="left" colspan="2" styleCode="Lrule" valign="top">&#x25CB; coma</td><td align="left" colspan="3" styleCode="Rrule" valign="top">&#x25CB; shaking (tremors), stiff muscles, or muscle twitching</td></tr><tr><td align="left" colspan="2" styleCode="Lrule" valign="top">&#x25CB; fast heart beat</td><td align="left" colspan="3" styleCode="Rrule" valign="top">&#x25CB; loss of coordination</td></tr><tr><td align="left" colspan="2" styleCode="Lrule" valign="top">&#x25CB; changes in blood pressure</td><td align="left" colspan="3" styleCode="Rrule" valign="top">&#x25CB; seizures</td></tr><tr><td align="left" colspan="2" styleCode="Lrule" valign="top">&#x25CB; dizziness</td><td align="left" colspan="3" styleCode="Rrule" valign="top">&#x25CB; nausea, vomiting, diarrhea</td></tr><tr><td align="left" colspan="5" styleCode="Lrule Rrule" valign="top">&#x25CF; <content styleCode="bold">Eye problems (angle-closure glaucoma).</content>Paroxetine tablets may cause a type of eye problem called angle-closure glaucoma in people with certain other eye conditions. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are. Call your healthcare provider if you have eye pain, changes in your vision, or swelling or redness in or around the eye. &#x25CF; <content styleCode="bold">Medicine interactions.</content>Taking paroxetine tablets with certain other medicines including thioridazine and pimozide may increase the risk of developing a serious heart problem called QT prolongation. &#x25CF; <content styleCode="bold">Seizures (convulsions).</content> &#x25CF; <content styleCode="bold">Manic episodes.</content>Manic episodes may happen in people with bipolar disorder who take paroxetine tablets.

idazine and pimozide may increase the risk of developing a serious heart problem called QT prolongation. &#x25CF; <content styleCode="bold">Seizures (convulsions).</content> &#x25CF; <content styleCode="bold">Manic episodes.</content>Manic episodes may happen in people with bipolar disorder who take paroxetine tablets. Symptoms may include: </td></tr><tr><td align="left" colspan="2" styleCode="Lrule" valign="top">&#x25CB; greatly increased energy</td><td align="left" colspan="3" styleCode="Rrule" valign="top">&#x25CB; severe problems sleeping</td></tr><tr><td align="left" colspan="2" styleCode="Lrule" valign="top">&#x25CB; racing thoughts</td><td align="left" colspan="3" styleCode="Rrule" valign="top">&#x25CB; reckless behavior</td></tr><tr><td align="left" colspan="2" styleCode="Lrule" valign="top">&#x25CB; unusually grand ideas</td><td align="left" colspan="3" styleCode="Rrule" valign="top">&#x25CB; excessive happiness or irritability</td></tr><tr><td align="left" colspan="2" styleCode="Lrule" valign="top">&#x25CB; talking more or faster than usual</td><td colspan="3" styleCode="Rrule" valign="top"/></tr><tr><td align="left" colspan="5" styleCode="Lrule Rrule" valign="top"><content styleCode="bold"> &#x25CF; Discontinuation syndrome.</content>Suddenly stopping paroxetine tablets may cause you to have serious side effects. Your healthcare provider may want to decrease your dose slowly. Symptoms may include: </td></tr><tr><td align="left" styleCode="Lrule" valign="top">&#x25CB; nausea</td><td align="left" colspan="3" valign="top">&#x25CB; electric shock feeling (paresthesia)</td><td align="left" styleCode="Rrule" valign="top">&#x25CB; tiredness</td></tr><tr><td align="left" styleCode="Lrule" valign="top">&#x25CB; sweating</td><td align="left" colspan="3" valign="top">&#x25CB; tremor</td><td align="left" styleCode="Rrule" valign="top">&#x25CB; problems sleeping</td></tr><tr><td align="left" styleCode="Lrule" valign="top">&#x25CB; changes in your mood</td><td align="left" colspan="3" valign="top">&#x25CB; anxiety</td><td align="left" styleCode="Rrule" valign="top">&#x25CB; hypomania</td></tr><tr><td align="left" styleCode="Lrule" valign="top">irritability and agitation</td><td align="left" colspan="3" valign="top">&#x25CB; confusion</td><td align="left" styleCode="Rrule" valign="top">&#x25CB; ringing in your ears (tinnitus)</td></tr><tr><td align="left" styleCode="Lrule" valign="top">&#x25CB; dizziness</td><td align="left" colspan="3" valign="top">&#x25CB; headache</td><td align="left" styleCode="Rrule" valign="top">&#x25CB; seizures</td></tr><tr><td align="left" colspan="5" styleCode="Lrule Rrule" valign="top"><content styleCode="bold">&#x25CF; Low sodium levels in your blood (hyponatremia).</content>Low sodium levels in your blood that may be serious and may cause death, can happen during treatment with paroxetine tablets. Elderly people and people who take certain medicines may be at a greater risk for developing low sodium levels in your blood. Signs and symptoms may include: &#x25CB; headache &#x25CB; difficulty concentrating &#x25CB; memory changes &#x25CB; confusion &#x25CB; weakness and unsteadiness on your feet which can lead to falls <content styleCode="bold"> In more severe or more sudden cases, signs and symptoms include:</content> &#x25CB; seeing or hearing things that are not real (hallucinations) &#x25CB; fainting &#x25CB; seizures &#x25CB; coma &#x25CB; stopping breathing (respiratory arrest) <content styleCode="bold">&#x25CF; Abnormal bleeding.</content>Taking paroxetine tablets with aspirin, NSAIDs, or blood thinners may increase this risk. Tell your healthcare provider about any unusual bleeding or bruising.

#x25CB; fainting &#x25CB; seizures &#x25CB; coma &#x25CB; stopping breathing (respiratory arrest) <content styleCode="bold">&#x25CF; Abnormal bleeding.</content>Taking paroxetine tablets with aspirin, NSAIDs, or blood thinners may increase this risk. Tell your healthcare provider about any unusual bleeding or bruising. <content styleCode="bold">&#x25CF; Bone fractures.</content> <content styleCode="bold">&#x25CF; </content><content styleCode="bold">Sexual problems (dysfunction).</content>Taking selective serotonin reuptake inhibitors (SSRIs), including paroxetine, may cause sexual problems. Symptoms in males may include: o Delayed ejaculation or inability to have an ejaculation o Decreased sex drive o Problems getting or keeping an erection Symptoms in females may include: o Decreased sex drive o Delayed orgasm or inability to have an orgasm Talk to your healthcare provider if you develop any changes in your sexual function or if you have any questions or concerns about sexual problems during treatment with paroxetine. There may be treatments your healthcare provider can suggest. <content styleCode="bold">The most common side effects of paroxetine tablets include:</content> </td></tr><tr><td align="left" colspan="3" styleCode="Lrule" valign="top">&#x25CB; male and female sexual function problems</td><td align="left" colspan="2" styleCode="Rrule" valign="top">&#x25CB; weakness (asthenia)</td></tr><tr><td align="left" colspan="3" styleCode="Lrule" valign="top">&#x25CB; constipation</td><td align="left" colspan="2" styleCode="Rrule" valign="top">&#x25CB; decreased appetite</td></tr><tr><td align="left" colspan="3" styleCode="Lrule" valign="top">&#x25CB; diarrhea</td><td align="left" colspan="2" styleCode="Rrule" valign="top">&#x25CB; dizziness</td></tr><tr><td align="left" colspan="3" styleCode="Lrule" valign="top">&#x25CB; dry mouth</td><td align="left" colspan="2" styleCode="Rrule" valign="top">&#x25CB; infection</td></tr><tr><td align="left" colspan="3" styleCode="Lrule" valign="top">&#x25CB; problems sleeping</td><td align="left" colspan="2" styleCode="Rrule" valign="top">&#x25CB; nausea</td></tr><tr><td align="left" colspan="3" styleCode="Lrule" valign="top">&#x25CB; nervousness</td><td align="left" colspan="2" styleCode="Rrule" valign="top">&#x25CB; sleepiness</td></tr><tr><td align="left" colspan="3" styleCode="Lrule" valign="top">&#x25CB; sweating</td><td align="left" colspan="2" styleCode="Rrule" valign="top">&#x25CB; shaking (tremor)</td></tr><tr><td align="left" colspan="3" styleCode="Lrule" valign="top">&#x25CB; yawning</td><td colspan="2" styleCode="Rrule" valign="top"/></tr><tr><td align="left" colspan="5" styleCode="Lrule Botrule Rrule" valign="top">These are not all the possible side effects of paroxetine tablets. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. </td></tr><tr><td align="left" colspan="5" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">How should I store paroxetine tablets?</content><list listType="unordered" styleCode="Disc"><item>Store paroxetine tablets between 68&#xB0;F to 77&#xB0;F (20&#xB0;C to 25&#xB0;C).</item><item>Paroxetine tablets come in child-resistant bottle pack of 30&apos;s and 90&apos;s.</item></list><content styleCode="bold">Keep paroxetine tablets and all medicines out of the reach of children.</content></td></tr><tr><td align="left" colspan="5" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">General information about the safe and effective use of paroxetine tablets.</content> Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not take paroxetine tablets for a condition for which it was not prescribed.

Lrule Botrule Rrule" valign="top"><content styleCode="bold">General information about the safe and effective use of paroxetine tablets.</content> Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not take paroxetine tablets for a condition for which it was not prescribed. Do not give paroxetine tablets to other people, even if they have the same symptoms that you have. It may harm them. You may ask your healthcare provider or pharmacist for information about paroxetine tablets that is written for healthcare professionals. </td></tr><tr><td align="left" colspan="5" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">What are the ingredients in paroxetine tablets?</content> <content styleCode="bold">Active ingredient:</content>paroxetine hydrochloride, USP <content styleCode="bold">Inactive ingredients:</content>dibasic calcium phosphate anhydrous, hypromellose 6 cP, lactose anhydrous, magnesium stearate, polyethylene glycol 6000, povidone, sodium starch glycolate, talc, and titanium dioxide. Medication Guide available at www.zydususa.com/medguides or call 1-877-993-8779. </td></tr><tr><td align="center" colspan="5" styleCode="Lrule Botrule Rrule" valign="top"><paragraph><content styleCode="bold">Repackaged and Distributed By:</content></paragraph><paragraph><content styleCode="bold">Remedy Repack, Inc.</content></paragraph><paragraph><content styleCode="bold">625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762</content></paragraph></td></tr><tr><td align="right" colspan="5" styleCode="Lrule Botrule Rrule" valign="top">Rev.: 01/25</td></tr></tbody></table>

3 DOSAGE FORMS AND STRENGTHS Paroxetine tablets, USP are available as: 30 mg: White to off-white, round-shaped, biconvex, film- coated tablets debossed with the logo of 'ZC17' on one side and plain on other side Tablets: 30 mg tablets. ( 3 )

16 HOW SUPPLIED/STORAGE AND HANDLING Paroxetine Tablets USP, 30 mg are white to off-white, round-shaped, biconvex, film-coated tablets debossed with the logo of 'ZC17' on one side and plain on other side, and are supplied as follows: NDC: 70518-2465-00 NDC: 70518-2465-01 NDC: 70518-2465-02 NDC: 70518-2465-03 PACKAGING: 30 in 1 BLISTER PACK PACKAGING: 90 in 1 BOTTLE PLASTIC PACKAGING: 90 in 1 BOTTLE PLASTIC PACKAGING: 30 in 1 BLISTER PACK Store at 20°C to 25° C (68°F to 77° F) [See USP Controlled Room Temperature]. Repackaged and Distributed By: Remedy Repack, Inc. 625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762

ing. Taking paroxetine tablets with aspirin, NSAIDs, or blood thinners may increase this risk. Tell your healthcare provider about any unusual bleeding or bruising. ● Bone fractures. ● Sexual problems (dysfunction). Taking selective serotonin reuptake inhibitors (SSRIs), including paroxetine, may cause sexual problems. Symptoms in males may include: o Delayed ejaculation or inability to have an ejaculation o Decreased sex drive o Problems getting or keeping an erection Symptoms in females may include: o Decreased sex drive o Delayed orgasm or inability to have an orgasm Talk to your healthcare provider if you develop any changes in your sexual function or if you have any questions or concerns about sexual problems during treatment with paroxetine. There may be treatments your healthcare provider can suggest. The most common side effects of paroxetine tablets include: ○ male and female sexual function problems ○ weakness (asthenia) ○ constipation ○ decreased appetite ○ diarrhea ○ dizziness ○ dry mouth ○ infection ○ problems sleeping ○ nausea ○ nervousness ○ sleepiness ○ sweating ○ shaking (tremor) ○ yawning These are not all the possible side effects of paroxetine tablets. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store paroxetine tablets? Store paroxetine tablets between 68°F to 77°F (20°C to 25°C). Paroxetine tablets come in child-resistant bottle pack of 30's and 90's. Keep paroxetine tablets and all medicines out of the reach of children. General information about the safe and effective use of paroxetine tablets. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not take paroxetine tablets for a condition for which it was not prescribed. Do not give paroxetine tablets to other people, even if they have the same symptoms that you have. It may harm them. You may ask your healthcare provider or pharmacist for information about paroxetine tablets that is written for healthcare professionals. What are the ingredients in paroxetine tablets? Active ingredient: paroxetine hydrochloride, USP Inactive ingredients: dibasic calcium phosphate anhydrous, hypromellose 6 cP, lactose anhydrous, magnesium stearate, polyethylene glycol 6000, povidone, sodium starch glycolate, talc, and titanium dioxide. Medication Guide available at www.zydususa.com/medguides or call 1-877-993-8779. Rev.: 01/25 This Medication Guide has been approved by the U.S. Food and Drug Administration. Repackaged By / Distributed By: RemedyRepack Inc. 625 Kolter Drive, Indiana, PA 15701 (724) 465-8762

Lrule Botrule Rrule" valign="top"><content styleCode="bold">General information about the safe and effective use of paroxetine tablets.</content> Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not take paroxetine tablets for a condition for which it was not prescribed. Do not give paroxetine tablets to other people, even if they have the same symptoms that you have. It may harm them. You may ask your healthcare provider or pharmacist for information about paroxetine tablets that is written for healthcare professionals. </td></tr><tr><td align="left" colspan="5" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">What are the ingredients in paroxetine tablets?</content> <content styleCode="bold">Active ingredient:</content>paroxetine hydrochloride, USP <content styleCode="bold">Inactive ingredients:</content>dibasic calcium phosphate anhydrous, hypromellose 6 cP, lactose anhydrous, magnesium stearate, polyethylene glycol 6000, povidone, sodium starch glycolate, talc, and titanium dioxide. Medication Guide available at www.zydususa.com/medguides or call 1-877-993-8779. </td></tr><tr><td align="center" colspan="5" styleCode="Lrule Botrule Rrule" valign="top"/></tr><tr><td align="right" colspan="5" styleCode="Lrule Botrule Rrule" valign="top">Rev.: 01/25</td></tr></tbody></table>

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors [see Warnings and Precautions (5.1)] . Paroxetine extended-release tablets are not approved for use in pediatric patients [see Use in Specific Populations (8.4)] . WARNING: SUICIDAL THOUGHTS AND BEHAVIORS See full prescribing information for complete boxed warning. Increased risk of suicidal thoughts and behavior in pediatric and young adult patients taking antidepressants. Closely monitor all antidepressant- treated patients for clinical worsening and emergence of suicidal thoughts and behaviors. Paroxetine extended-release tablets are not approved for use in pediatric patients. (5.1, 8.4)

1 INDICATIONS AND USAGE Paroxetine extended-release tablets are indicated in adults for the treatment of: • Major depressive disorder (MDD) • Panic disorder (PD) • Social anxiety disorder (SAD) • Premenstrual dysphoric disorder (PMDD) Paroxetine extended-release tablets are selective serotonin reuptake inhibitor (SSRI) indicated in adults for the treatment of (1): • Major Depressive Disorder (MDD) • Panic Disorder (PD) • Social Anxiety Disorder (SAD) • Premenstrual Dysphoric Disorder (PMDD)

2 DOSAGE AND ADMINISTRATION • Swallow tablet whole; do not chew or crush. (2.1) • Recommended starting and maximum daily dosage: (2.2, 2.3) Indication Starting Dose Maximum Dose MDD 25 mg/day 62.5 mg/day PD 12.5 mg/day 75 mg/day SAD 12.5 mg/day 37.5 mg/day PMDD 12.5 mg/day 25 mg/day • For PMDD, dose continuously or intermittently (luteal phase only). (2.3) • If inadequate response to starting dosage, titrate in 12.5 mg per day increments once weekly. (2.2, 2.3) • Elderly patients, patients with severe renal impairment or severe hepatic impairment: Starting dose is 12.5 mg per day. Do not exceed 50 mg per day for treatment of MDD and PD and 37.5 mg per day for treatment of SAD. (2.5) • When discontinuing paroxetine extended-release tablets, reduce dose gradually. (2.7) 2.1 Important Administration Instructions Administer paroxetine extended-release tablets as a single daily dose in the morning, with or without food. Swallow tablets whole and do not chew or crush. 2.2 Dosage in Patients with Major Depressive Disorder, Panic Disorder, and Social Anxiety Disorder The recommended initial dosage and maximum dosage of paroxetine extended-release tablets in patients with MDD, PD, and SAD are presented in Table 1. In patients with an inadequate response, dosage may be increased in increments of 12.5 mg per day at intervals of at least 1 week, depending on tolerability. Table 1: Recommended Daily Dosage of Paroxetine Extended-Release Tablets in Patients with MDD, PD, and SAD Indication Starting Dose Maximum Dose MDD 25 mg 62.5 mg PD 12.5 mg 75 mg SAD 12.5 mg 37.5 mg 2.3 Dosage in Patients with Premenstrual Dysphoric Disorder The recommended starting dosage in women with PMDD is 12.5 mg per day. Paroxetine extended-release tablets may be administered either continuously (every day throughout the menstrual cycle) or intermittently (only during the luteal phase of the menstrual cycle, i.e., starting the daily dosage 14 days prior to the anticipated onset of menstruation and continuing through the onset of menses). Intermittent dosing is repeated with each new cycle. In patients with an inadequate response, the dosage may be increased to the maximum recommended dosage of 25 mg per day, depending on tolerability. Institute dosage adjustments at intervals of at least 1 week. 2.4 Screen for Bipolar Disorder Prior to Starting Paroxetine Extended-Release Tablets Prior to initiating treatment with paroxetine extended-release tablets or another antidepressant, screen patients for a personal or family history of bipolar disorder, mania, or hypomania [see Warnings and Precautions (5.6)]. 2.5 Dosage Modifications for Elderly Patients, Patients with Severe Renal Impairment and Patients with Severe Hepatic Impairment The recommended initial dose of paroxetine extended-release tablets are 12.5 mg per day for elderly patients, patients with severe renal impairment, and patients with severe hepatic impairment. Reduce initial dose and increase up-titration intervals if necessary. Dosage should not exceed 50 mg per day for MDD or PD and should not exceed 37.5 mg per day for SAD [see Use in Specific Populations (8.5, 8.6)]. 2.6 Switching Patients to or from a Monoamine Oxidase Inhibitor Antidepressant At least 14 days must elapse between discontinuation of an monoamine oxidase inhibitor (MAOI) antidepressant and initiation of paroxetine extended-release tablets.

exceed 37.5 mg per day for SAD [see Use in Specific Populations (8.5, 8.6)]. 2.6 Switching Patients to or from a Monoamine Oxidase Inhibitor Antidepressant At least 14 days must elapse between discontinuation of an monoamine oxidase inhibitor (MAOI) antidepressant and initiation of paroxetine extended-release tablets. In addition, at least 14 days must elapse after stopping paroxetine extended-release tablets before starting an MAOI antidepressant [see Contraindications (4), Warnings and Precautions (5.2)] . 2.7 Discontinuation of Treatment with Paroxetine Extended-Release Tablets Adverse reactions may occur upon discontinuation of paroxetine extended-release tablets [see Warnings and Precautions (5.7)] . Gradually reduce the dosage rather than stopping paroxetine extended-release tablets abruptly whenever possible.

3 DOSAGE FORMS AND STRENGTHS Paroxetine extended-release tablets, USP are available as: • 12.5 mg, yellow colored, round, biconvex, beveled edge film coated tablets, debossed with “L587” on one side and plain on other side. • 25 mg, pink colored, round, biconvex, beveled edge film coated tablets, debossed with “L588” on one side and plain on other side. • 37.5 mg, blue colored, round, biconvex, beveled edge film coated tablets, debossed with “L589” on one side and plain on other side. Extended-release tablets: 12.5 mg, 25 mg, and 37.5 mg tablets. (3)

4 CONTRAINDICATIONS Paroxetine extended-release tablets are contraindicated in patients: • Taking, or within 14 days of stopping, MAOIs (including the MAOIs linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [See Warnings and Precautions (5.2), Drug Interactions (7)]. • Taking thioridazine because of risk of QT prolongation [see Warnings and Precautions (5.3), Drug Interactions (7)]. • Taking pimozide because of risk of QT prolongation [see Warnings and Precautions (5.3), Drug Interactions (7)]. • With known hypersensitivity (e.g., anaphylaxis, angioedema, Stevens-Johnson syndrome) to paroxetine or to any of the inactive ingredients in paroxetine extended-release tablets [see Adverse Reactions (6.1, 6.2)] . • Concomitant use of monoamine oxidase inhibitors (MAOIs) or use within 14 days of discontinuing a MAOIs. (4, 5.2, 7) • Concomitant use of pimozide or thioridazine. (4, 5.3, 7) • Known hypersensitivity to paroxetine extended-release tablets or to any of the inactive ingredients in paroxetine extended-release tablets. (4)

5 WARNINGS AND PRECAUTIONS • Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents, but also when taken alone. If occurs, discontinue paroxetine and serotonergic agents and initiate supportive measures. (5.2) • Embryofetal Toxicity: May cause fetal harm. Meta-analysis of epidemiological studies have shown increased risk (less than 2-fold) of cardiovascular malformations with exposure during the first trimester. (5.4, 8.1) • Increased Risk of Bleeding: Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, other antiplatelet drugs, warfarin, and other anticoagulant drugs may increase risk. (5.5) • Activation of Mania/Hypomania: Screen patients for bipolar disorder. (5.6) • Seizures: Use with caution in patients with seizure disorders. (5.8) • Angle-Closure Glaucoma: Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles, treated with antidepressants. (5.9) • Sexual Dysfunction: Paroxetine may cause symptoms of sexual dysfunction. (5.13) 5.1 Suicidal Thoughts and Behaviors in Adolescents and Young Adults In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater than in placebo-treated patients. There was considerable variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied. There were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with MDD. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1000 patients treated are provided in Table 2. Table 2: Risk Differences of the Number of Patients of Suicidal Thoughts and Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients Age Range Drug-Placebo Difference in Number of Patients of Suicidal Thoughts and Behaviors per 1,000 Patients Treated Increases Compared to Placebo <18 years old 14 additional patients 18 to 24 years old 5 additional patients Decreases Compared to Placebo 25 to 64 years old 1 fewer patient ≥65 years old 6 fewer patients It is unknown whether the risk of suicidal thoughts and behaviors in children, adolescents, and young adults extends to longer-term use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with MDD that antidepressants delay the recurrence of depression and that depression itself is a risk factor for suicidal thoughts and behaviors. Monitor all antidepressant-treated patients for any indication for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy, and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing paroxetine, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.

l family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing paroxetine, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors. 5.2 Serotonin Syndrome Serotonin-norepinephrine reuptake inhibitors (SNRIs) and SSRIs, including paroxetine, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines, and St. John's Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [see Contraindications (4), Drug Interactions (7.1)] . Serotonin syndrome can also occur when these drugs are used alone. Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The concomitant use of paroxetine with MAOIs is contraindicated. In addition, do not initiate paroxetine in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection). If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking paroxetine, discontinue paroxetine before initiating treatment with the MAOI [see Contraindications (4), Drug Interactions (7.1)] . Monitor all patients taking paroxetine for the emergence of serotonin syndrome. Discontinue treatment with paroxetine and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of paroxetine with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms. 5.3 Drug Interactions Leading to QT Prolongation The CYP2D6 inhibitory properties of paroxetine can elevate plasma levels of thioridazine and pimozide. Since thioridazine and pimozide given alone produce prolongation of the QTc interval and increase the risk of serious ventricular arrhythmias, the use of paroxetine is contraindicated in combination with thioridazine and pimozide [see Contraindications (4), Drug Interactions (7), Clinical Pharmacology (12.3)] . 5.4 Embryofetal Toxicity Based on meta-analyses of epidemiological studies, exposure to paroxetine in the first trimester of pregnancy is associated with a less than 2-fold increase in the rate of cardiovascular malformations among infants. For women who intend to become pregnant or who are in their first trimester of pregnancy, paroxetine, should be initiated only after consideration of the other available treatment options [see Use in Specific Populations (8.1)] . 5.5 Increased Risk of Bleeding Drugs that interfere with serotonin reuptake inhibition, including paroxetine, increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDS), other antiplatelet drugs, warfarin, and other anticoagulants may add to this risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding.

atory drugs (NSAIDS), other antiplatelet drugs, warfarin, and other anticoagulants may add to this risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Based on data from the published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Use in Specific Populations (8.1)] . Bleeding events related to drugs that interfere with serotonin reuptake have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages. Inform patients about the increased risk of bleeding associated with the concomitant use of paroxetine and antiplatelet agents or anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio. 5.6 Activation of Mania or Hypomania In patients with bipolar disorder, treating a depressive episode with paroxetine or another antidepressant may precipitate a mixed/manic episode. During controlled clinical trials of immediate-release paroxetine hydrochloride, hypomania or mania occurred in approximately 1% of paroxetine-treated unipolar patients compared to 1.1% of active-control and 0.3% of placebo-treated unipolar patients. Prior to initiating treatment with paroxetine, screen patients for any personal or family history of bipolar disorder, mania, or hypomania. 5.7 Discontinuation Syndrome Adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt discontinuation, include: nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia, such as electric shock sensations), tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible [See Dosage and Administration (2.7)] . Adverse reactions have been reported upon discontinuation of treatment with paroxetine in pediatric patients. The safety and effectiveness of paroxetine in pediatric patients have not been established [see Boxed Warning, Warnings and Precautions (5.1), Use in Specific Populations (8.4)]. 5.8 Seizures Paroxetine has not been systematically evaluated in patients with seizure disorders. Patients with history of seizures were excluded from clinical studies. Paroxetine should be prescribed with caution in patients with a seizure disorder and should be discontinued in any patient who develops seizures. 5.9 Angle-Closure Glaucoma The pupillary dilation that occurs following use of many antidepressant drugs including paroxetine may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy. Cases of angle-closure glaucoma associated with use of paroxetine hydrochloride tablets have been reported. Avoid use of antidepressants, including paroxetine extended-release tablets, in patients with untreated anatomically narrow angles. 5.10 Hyponatremia Hyponatremia may occur as a result of treatment with SNRIs and SSRIs, including paroxetine. Cases with serum sodium lower than 110 mmol/L have been reported. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls. Signs and symptoms associated with more severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest and death. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH).

d unsteadiness, which may lead to falls. Signs and symptoms associated with more severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest and death. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). In patients with symptomatic hyponatremia, discontinue paroxetine and institute appropriate medical intervention. Elderly patients, patients taking diuretics, and those who are volume-depleted may be at greater risk of developing hyponatremia with SNRIs and SSRIs [see Use in Specific Populations (8.5)] . 5.11 Reduction of Efficacy of Tamoxifen Some studies have shown that the efficacy of tamoxifen, as measured by the risk of breast cancer relapse/mortality, may be reduced with concomitant use of paroxetine as a result of paroxetine’s irreversible inhibition of CYP2D6 and lower blood levels of tamoxifen [see Drug Interactions (7.1)] . One study suggests that the risk may increase with longer duration of coadministration. However, other studies have failed to demonstrate such a risk. When tamoxifen is used for the treatment or prevention of breast cancer, prescribers should consider using an alternative antidepressant with little or no CYP2D6 inhibition. 5.12 Bone Fracture Epidemiological studies on bone fracture risk during exposure to some antidepressants, including SSRIs, have reported an association between antidepressant treatment and fractures. There are multiple possible causes for this observation, and it is unknown to what extent fracture risk is directly attributable to SSRI treatment. 5.13 Sexual Dysfunction Use of SSRIs, including paroxetine, may cause symptoms of sexual dysfunction [see Adverse Reactions (6.1)] . In male patients, SSRI use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction. In female patients, SSRI use may result in decreased libido and delayed or absent orgasm. It is important for prescribers to inquire about sexual function prior to initiation of paroxetine and to inquire specifically about changes in sexual function during treatment, because sexual function may not be spontaneously reported. When evaluating changes in sexual function, obtaining a detailed history (including timing of symptom onset) is important because sexual symptoms may have other causes, including the underlying psychiatric disorder. Discuss potential management strategies to support patients in making informed decisions about treatment.

<table cellspacing="0" cellpadding="0" border="0" width="0"><colgroup><col width="22.6102292768959%"/><col width="77.3897707231041%"/></colgroup><thead><tr><th styleCode="Lrule Rrule Toprule" align="center"> <content styleCode="bold">Age Range</content> </th><th styleCode="Lrule Rrule Toprule" align="center"> <content styleCode="bold">Drug-Placebo Difference in Number of Patients of Suicidal Thoughts and Behaviors per 1,000 Patients Treated</content> </th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">Increases Compared to Placebo</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" align="center" valign="top"> &lt;18 years old </td><td styleCode="Rrule" align="center" valign="top"> 14 additional patients </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" align="center" valign="top"> 18 to 24 years old </td><td styleCode="Rrule" align="center" valign="top"> 5 additional patients </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">Decreases Compared to Placebo</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" align="center" valign="top"> 25 to 64 years old </td><td styleCode="Rrule" align="center" valign="top"> 1 fewer patient </td></tr><tr><td styleCode="Lrule Rrule" align="center" valign="top"> &#x2265;65 years old </td><td styleCode="Rrule" align="center" valign="top"> 6 fewer patients </td></tr></tbody></table>

6 ADVERSE REACTIONS The following adverse reactions are included in more detail in other sections of the prescribing information: • Hypersensitivity reactions to paroxetine [see Contraindications (4)] • Suicidal Thoughts and Behaviors [see Warnings and Precautions (5.1)] • Serotonin Syndrome [see Warnings and Precautions (5.2)] • Embryofetal and Neonatal Toxicity [see Warnings and Precautions (5.4)] • Increased Risk of Bleeding [see Warnings and Precautions (5.5)] • Activation of Mania/Hypomania [see Warnings and Precautions (5.6)] • Discontinuation Syndrome [see Warnings and Precautions (5.7)] • Seizures [see Warnings and Precautions (5.8)] • Angle-closure Glaucoma [see Warnings and Precautions (5.9)] • Hyponatremia [see Warnings and Precautions (5.10)] • Bone Fracture [see Warnings and Precautions (5.12)] • Sexual Dysfunction [see Warnings and Precautions (5.13)] Most common adverse reactions (≥5% and at least twice placebo) in placebo-controlled MDD, PD, SAD, and PMDD clinical trials: abnormal ejaculation, abnormal vision, asthenia, constipation, decreased appetite, diarrhea, dizziness, dry mouth, female genital disorder, impotence, insomnia, libido decreased, nausea, somnolence, sweating, tremor. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Safety data for paroxetine extended-release tablets is from 11 short-term, placebo-controlled clinical trials including 3 studies in patients with major depressive disorder (MDD) (Studies 1, 2, and 3), 3 studies in patients with panic disorder (PD) (Studies 4, 5, and 6), 1 study in patients with social anxiety disorder (SAD) (Study 7), and 4 studies in female patients with premenstrual dysphoric disorder (PMDD) (Studies 8, 9, 10, and 11) [see Clinical Studies (14)] . These 11 trials included 1627 patients treated with paroxetine extended-release tablets. • Studies 1 and 2 were 12-week studies that enrolled patients 18 to 65 years old who received paroxetine extended-release tablets at doses ranging from 25 mg to 62.5 mg once daily. Study 3 was a 12-week study in patients 60 to 88 years old who received paroxetine extended-release tablets at doses ranging from 12.5 mg to 50 mg once daily. • Studies 4, 5, and 6 were 10-week studies in patients 19 to 72 years old who received paroxetine extended-release tablets at doses ranging from 12.5 mg to 75 mg once daily. • Study 7 was a 12-week study that enrolled adult patients who received paroxetine extended-release tablets at doses ranging from 12.5 mg to 37.5 mg once daily. • Studies 8, 9, and 10 were 12-week, placebo-controlled trials in female patients 18 to 46 years old who received paroxetine extended-release tablets at doses of 12.5 mg or 25 mg once daily. Study 11 was a 12-week placebo-controlled trial in patients 18 to 46 years old who received paroxetine extended-release tablets 2 weeks prior to the onset of menses (luteal phase dosing) at doses of 12.5 mg or 25 mg once daily.

ld who received paroxetine extended-release tablets at doses of 12.5 mg or 25 mg once daily. Study 11 was a 12-week placebo-controlled trial in patients 18 to 46 years old who received paroxetine extended-release tablets 2 weeks prior to the onset of menses (luteal phase dosing) at doses of 12.5 mg or 25 mg once daily. Adverse Reactions Leading to Discontinuation in Patients with MDD, PD, SAD, and PMDD In pooled studies in patients with MDD, PD and SAD, the most common adverse reactions leading to study withdrawal were: nausea (up to 4% of patients), asthenia, headache, depression, insomnia, and abnormal liver function tests (each occurring in up to 2% of patients), and dizziness, somnolence, and diarrhea (each occurring in up to 1% of patients). In pooled studies for PMDD, the most common adverse reactions leading to study withdrawal were: nausea (occurring in up to 6% of patients), asthenia (occurring in up to 5% of patients), somnolence (occurring in up to 4% of patients), insomnia (occurring in approximately 2% of patients); and impaired concentration, dry mouth, dizziness, decreased appetite, sweating, tremor, yawn and diarrhea (occurring in less than or equal to 2% of patients). Adverse Reactions in MDD, PD, and SAD Table 3 presents the most common adverse reactions in paroxetine extended-release tablets-treated patients (incidence ≥5% and greater than placebo within at least 1 of the indications) in controlled trials in patients with MDD, PD, and SAD.

in less than or equal to 2% of patients). Adverse Reactions in MDD, PD, and SAD Table 3 presents the most common adverse reactions in paroxetine extended-release tablets-treated patients (incidence ≥5% and greater than placebo within at least 1 of the indications) in controlled trials in patients with MDD, PD, and SAD. Table 3: Adverse Reactions (≥5% of Patients Treated with Paroxetine Extended-Release Tablets and Greater than Placebo) in 10 to 12 Week Studies of MDD, PD, and SAD MDD 18 to 65 year olds MDD ≥60 years old Panic Disorder Social Anxiety Disorder Body System/ Adverse Reaction Paroxetine Extended-Release Tablets (N=212) % Placebo (N=211) % Paroxetine Extended-Release Tablets (N=104) % Placebo (N=109) % Paroxetine Extended-Release Tablets (N=444) % Placebo (N=445) % Paroxetine Extended-Release Tablets (N=186) % Placebo (N=184) % Body as a Whole Headache 27 20 17 13 NA NA 23 17 Asthenia 14 9 15 14 15 10 18 7 Abdominal Pain 7 4 - - 6 4 5 4 Back Pain 5 3 - - NA NA 4 1 Digestive System Nausea 22 10 - - 23 17 22 6 Diarrhea 18 7 15 9 12 9 9 8 Dry Mouth 15 8 18 7 13 9 3 2 Constipation 10 4 13 5 9 6 5 2 Flatulence 6 4 - - NA NA NA NA Decreased Appetite 2 12 5 8 6 1 <1 Dyspepsia NA NA 13 10 NA NA 2 <1 Musculoskeletal System Myalgia NA NA - - 5 3 NA NA Nervous System Somnolence 22 8 21 12 20 9 9 4 Insomnia 17 9 10 8 20 11 9 4 Dizziness 14 4 9 5 NA NA 7 4 Libido Decreased 7 3 8 <1 9 4 1 Nervousness NA NA - - 8 7 NA NA Tremor 7 1 7 0 8 2 4 2 Anxiety NA NA - - 5 4 2 1 Respiratory System Sinusitis NA NA - - 8 5 NA NA Yawn 0 - - 3 0 2 0 Skin and Appendages Sweating 6 2 10 <1 7 2 14 3 Special Senses Abnormal Vision a 5 1 - - 3 <1 2 0 Urogenital System Abnormal Ejaculation b,c 26 1 17 3 27 3 15 1 Female Genital Disorder b,d 10 <1 - - 7 1 3 0 Impotence b 5 3 9 3 10 1 9 0 Hyphen = the reaction listed occurred in <5% of patients treated with paroxetine extended-release tablets NA = the adverse reaction listed did not occur in this group of patients a Mostly blurred vision b Based on the number of males or females c Mostly anorgasmia or delayed ejaculation d Mostly anorgasmia or delayed orgasm Other Adverse Reactions Observed During the Premarketing Evaluation of Paroxetine Extended-Release Tablets Adverse reactions from studies in MDD (not including Study 3 in elderly patients), PD, and SAD that occurred between 1% and 5% of patients treated with paroxetine extended-release tablets and at a rate greater than in placebo-treated patients include:, allergic reaction, tachycardia, vasodilatation, hypertension, migraine, vomiting, weight loss, weight gain, hypertonia, paresthesia, agitation, confusion, myoclonus, concentration impaired, depression, rhinitis, cough increased, bronchitis, photosensitivity, eczema, taste perversion, UTI, menstrual disorder, urinary frequency, urination impaired, and vaginitis. Adverse Reactions in Patients with PMDD Table 4 displays adverse reactions that occurred (incidence of 5% or more and greater than placebo within at least 1 of the studies) in patients treated with paroxetine extended-release tablets in Studies 8, 9, 10, and 11.

er, urinary frequency, urination impaired, and vaginitis. Adverse Reactions in Patients with PMDD Table 4 displays adverse reactions that occurred (incidence of 5% or more and greater than placebo within at least 1 of the studies) in patients treated with paroxetine extended-release tablets in Studies 8, 9, 10, and 11. Table 4: Adverse Reactions (≥5% of Patients Treated with Paroxetine Extended-Release Tablets and Greater than Placebo) in Pooled Studies PMDD (Studies 8, 9, 11), and in Study 10 a,b,c Body System / Adverse Reaction % Reporting Adverse Reaction Continuous Dosing Studies 8, 9, and 10 Luteal Phase Dosing Study 11 Paroxetine Extended-Release Tablets (n = 681) % Placebo (n = 349) % Paroxetine Extended-Release Tablets (n = 246) % Placebo (n = 120) % Body as a Whole Asthenia 17 6 15 4 Headache 15 12 NA NA Infection 6 4 NA NA Digestive System Nausea 17 7 18 2 Diarrhea 6 2 6 0 Constipation 5 1 2 <1 Nervous System Libido Decreased 12 5 9 6 Somnolence 9 2 3 <1 Insomnia 8 2 7 3 Dizziness 7 3 6 3 Tremor 4 <1 5 0 Skin and Appendages Sweating 7 <1 6 <1 Urogenital System Female Genital Disorders c 8 1 2 0 NA= the adverse reaction information is not available in this population. a <1% means greater than zero and less than 1%. b The luteal phase and continuous dosing PMDD trials were not designed for making direct comparisons between the 2 dosing regimens. c Mostly anorgasmia or difficulty achieving orgasm. Dose Dependent Adverse Reactions Comparison of the incidence of adverse reactions (placebo vs. 12.5 mg paroxetine extended-release tablets vs. 25 mg paroxetine extended-release tablets) from studies 8, 9, 10 showed the following adverse reactions to be dose-related: Nausea, somnolence, sweating, dry mouth, dizziness, decreased appetite, tremor, impaired concentration, yawn, paresthesia, hyperkinesia, and vaginitis. Male and Female Sexual Dysfunction Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of SSRI treatment. However, reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, in part because patients and healthcare providers may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in labeling may underestimate their actual incidence. The percentage of patients reporting symptoms of sexual dysfunction in the Studies 1 and 2 (nonelderly patients with MDD), 4, 5, 6, 7, 8, 9, 10, and 11 are presented in Table 5: Table 5: Adverse Reactions Related To Sexual Dysfunction In Patients Treated With Paroxetine Extended-Release Tablets in Pooled 10 to 12 Week Studies of MDD, PD, SAD, and PMDD Studies 1 and 2 % Studies 4, 5, and 6 % Study 7 % Studies 8, 9, and 11 (Continuous Dosing) % Study 10 (Luteal Phase Dosing) % Paroxetine Extended-Release Tablets Placebo Paroxetine Extended-Release Tablets Placebo Paroxetine Extended-Release Tablets Placebo Paroxetine Extended-Release Tablets Placebo Paroxetine Extended-Release Tablets Placebo n (males) 78 78 162 194 88 97 NA NA NA NA Decreased Libido 10 5 9 6 13 1 NA NA NA NA Abnormal ejaculation 26 1 27 3 15 1 NA NA NA NA Impotence 5 3 10 1% 9 0 NA NA NA NA n (females) 134 133 282 251 98 87 681 349 246 120 Decreased Libido 4 2 8 2 4 1 12 5 9 6 Orgasmic Disturbance 10 <1 7 1 3 0 8 1 2 0 NA = the adverse reaction listed did not occur in this group of patients. Paroxetine treatment has been associated with several cases of priapism. In those cases with a known outcome, patients recovered without sequelae.

87 681 349 246 120 Decreased Libido 4 2 8 2 4 1 12 5 9 6 Orgasmic Disturbance 10 <1 7 1 3 0 8 1 2 0 NA = the adverse reaction listed did not occur in this group of patients. Paroxetine treatment has been associated with several cases of priapism. In those cases with a known outcome, patients recovered without sequelae. Less Common Adverse Reactions The following adverse reactions occurred during the clinical studies of paroxetine extended-release tablets and are not included elsewhere in the labeling. Reactions are categorized by body system and listed in order of decreasing frequency according to the following definitions: Frequent adverse reactions are those occurring on 1 or more occasions in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1,000 patients; rare reactions are those occurring in fewer than 1/1,000 patients. Cardiovascular System : Infrequent was postural hypotension. Hemic and Lymphatic System : Rare was thrombocytopenia. Metabolic and Nutritional Disorders : Infrequent were generalized edema and hypercholesteremia. Nervous System : Infrequent were convulsion, akathisia, and manic reaction. Psychiatric : Infrequent were hallucinations. Skin and Appendages : Frequent was rash; infrequent was urticaria; rare was angioedema and erythema multiforme. Urogenital System : Infrequent was urinary retention; rare was urinary incontinence. 6.2 Postmarketing Experience The following reactions have been identified during post approval use of paroxetine. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Acute pancreatitis, elevated liver function tests (the most severe cases were deaths due to liver necrosis, and grossly elevated transaminases associated with severe liver dysfunction), Guillain-Barré syndrome, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), priapism, syndrome of inappropriate ADH secretion (SIADH), prolactinemia and galactorrhea; extrapyramidal symptoms which have included akathisia, bradykinesia, cogwheel rigidity, dystonia, hypertonia, trismus; status epilepticus, acute renal failure, pulmonary hypertension, allergic alveolitis, anosmia, hyposmia, anaphylaxis, eclampsia, laryngismus, optic neuritis, porphyria, restless legs syndrome (RLS), ventricular fibrillation, ventricular tachycardia (including torsade de pointes), hemolytic anemia, events related to impaired hematopoiesis (including aplastic anemia, pancytopenia, bone marrow aplasia, and agranulocytosis), and vasculitic syndromes (such as Henoch-Schönlein purpura).

<table cellspacing="0" cellpadding="0" border="0" width="0"><colgroup><col width=""/><col width=""/><col width=""/><col width=""/><col width=""/><col width=""/><col width=""/><col width=""/><col width=""/></colgroup><thead><tr><th styleCode="Lrule Rrule Toprule" align="center"> </th><th styleCode="Lrule Rrule Toprule" colspan="2" align="center"> <content styleCode="bold">MDD</content> <content styleCode="bold">18 to 65 year olds</content> <content styleCode="bold"> </content></th><th styleCode="Lrule Rrule Toprule" colspan="2" align="center"><content styleCode="bold"> </content><content styleCode="bold">MDD</content> <content styleCode="bold">&#x2265;60 years old</content> </th><th styleCode="Lrule Rrule Toprule" colspan="2" align="center"> <content styleCode="bold">Panic Disorder</content> </th><th styleCode="Lrule Rrule Toprule" colspan="2" align="center"> <content styleCode="bold">Social Anxiety</content> <content styleCode="bold">Disorder</content> </th></tr><tr><th styleCode="Lrule Rrule Toprule" align="center"> Body System/ Adverse Reaction </th><th styleCode="Lrule Rrule Toprule" align="center"> Paroxetine Extended-Release Tablets (N=212) % </th><th styleCode="Lrule Rrule Toprule" align="center"> Placebo (N=211) % </th><th styleCode="Lrule Rrule Toprule" align="center"> Paroxetine Extended-Release Tablets (N=104) % </th><th styleCode="Lrule Rrule Toprule" align="center"> Placebo (N=109) % </th><th styleCode="Lrule Rrule Toprule" align="center"> Paroxetine Extended-Release Tablets (N=444) % </th><th styleCode="Lrule Rrule Toprule" align="center"> Placebo (N=445) % </th><th styleCode="Lrule Rrule Toprule" align="center"> Paroxetine Extended-Release Tablets (N=186) % </th><th styleCode="Lrule Rrule Toprule" align="center"> Placebo (N=184) % </th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="bold">Body as a Whole</content> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" valign="top"> </td><td styleCode="Rrule" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Headache </td><td styleCode="Rrule" align="center" valign="top"> 27 </td><td styleCode="Rrule" align="center" valign="top"> 20 </td><td styleCode="Rrule" align="center" valign="top"> 17 </td><td styleCode="Rrule" align="center" valign="top"> 13 </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> 23 </td><td styleCode="Rrule" align="center" valign="top"> 17 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Asthenia </td><td styleCode="Rrule" align="center" valign="top"> 14 </td><td styleCode="Rrule" align="center" valign="top"> 9 </td><td styleCode="Rrule" align="center" valign="top"> 15 </td><td styleCode="Rrule" align="center" valign="top"> 14 </td><td styleCode="Rrule" align="center" valign="top"> 15 </td><td styleCode="Rrule" align="center" valign="top"> 10 </td><td styleCode="Rrule" align="center" valign="top"> 18 </td><td styleCode="Rrule" align="center" valign="top"> 7 </td></tr><tr styleCode="Botrule"><td styleCode="Lru

align="center" valign="top"> 14 </td><td styleCode="Rrule" align="center" valign="top"> 15 </td><td styleCode="Rrule" align="center" valign="top"> 10 </td><td styleCode="Rrule" align="center" valign="top"> 18 </td><td styleCode="Rrule" align="center" valign="top"> 7 </td></tr><tr styleCode="Botrule"><td styleCode="Lru le Rrule" valign="top"> Abdominal Pain </td><td styleCode="Rrule" align="center" valign="top"> 7 </td><td styleCode="Rrule" align="center" valign="top"> 4 </td><td styleCode="Rrule" align="center" valign="top"> - </td><td styleCode="Rrule" align="center" valign="top"> - </td><td styleCode="Rrule" align="center" valign="top"> 6 </td><td styleCode="Rrule" align="center" valign="top"> 4 </td><td styleCode="Rrule" align="center" valign="top"> 5 </td><td styleCode="Rrule" align="center" valign="top"> 4 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Back Pain </td><td styleCode="Rrule" align="center" valign="top"> 5 </td><td styleCode="Rrule" align="center" valign="top"> 3 </td><td styleCode="Rrule" align="center" valign="top"> - </td><td styleCode="Rrule" align="center" valign="top"> - </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> 4 </td><td styleCode="Rrule" align="center" valign="top"> 1 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="bold">Digestive System</content> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" valign="top"> </td><td styleCode="Rrule" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Nausea </td><td styleCode="Rrule" align="center" valign="top"> 22 </td><td styleCode="Rrule" align="center" valign="top"> 10 </td><td styleCode="Rrule" align="center" valign="top"> - </td><td styleCode="Rrule" align="center" valign="top"> - </td><td styleCode="Rrule" align="center" valign="top"> 23 </td><td styleCode="Rrule" align="center" valign="top"> 17 </td><td styleCode="Rrule" align="center" valign="top"> 22 </td><td styleCode="Rrule" align="center" valign="top"> 6 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Diarrhea </td><td styleCode="Rrule" align="center" valign="top"> 18 </td><td styleCode="Rrule" align="center" valign="top"> 7 </td><td styleCode="Rrule" align="center" valign="top"> 15 </td><td styleCode="Rrule" align="center" valign="top"> 9 </td><td styleCode="Rrule" align="center" valign="top"> 12 </td><td styleCode="Rrule" align="center" valign="top"> 9 </td><td styleCode="Rrule" align="center" valign="top"> 9 </td><td styleCode="Rrule" align="center" valign="top"> 8 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Dry Mouth </td><td styleCode="Rrule" align="center" valign="top"> 15 </td><td styleCode="Rrule" align="center" valign="top"> 8 </td><td styleCode="Rrule" align="center" valign="top"> 18 </td><td styleCode="Rrule" align="center" valign="top"> 7 </td><td styleCode="Rrule" align="center" valign="top"> 13 </td><td styleCode="Rrule" align="center" valign="top"> 9 </td><td styleCode="Rrule" align="center" valign="top"> 3 </td><td styleCode="Rrule" align="center" valign="top"> 2 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Constipation </td><td styleCode="Rrule" align="center" valign="top"> 10 </td><td styleCode="Rrule" align="center" valign="top"> 4 </td><td styleCode="Rrule" align="c

ter" valign="top"> 3 </td><td styleCode="Rrule" align="center" valign="top"> 2 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Constipation </td><td styleCode="Rrule" align="center" valign="top"> 10 </td><td styleCode="Rrule" align="center" valign="top"> 4 </td><td styleCode="Rrule" align="c enter" valign="top"> 13 </td><td styleCode="Rrule" align="center" valign="top"> 5 </td><td styleCode="Rrule" align="center" valign="top"> 9 </td><td styleCode="Rrule" align="center" valign="top"> 6 </td><td styleCode="Rrule" align="center" valign="top"> 5 </td><td styleCode="Rrule" align="center" valign="top"> 2 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Flatulence </td><td styleCode="Rrule" align="center" valign="top"> 6 </td><td styleCode="Rrule" align="center" valign="top"> 4 </td><td styleCode="Rrule" align="center" valign="top"> - </td><td styleCode="Rrule" align="center" valign="top"> - </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Decreased Appetite </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> 2 </td><td styleCode="Rrule" align="center" valign="top"> 12 </td><td styleCode="Rrule" align="center" valign="top"> 5 </td><td styleCode="Rrule" align="center" valign="top"> 8 </td><td styleCode="Rrule" align="center" valign="top"> 6 </td><td styleCode="Rrule" align="center" valign="top"> 1 </td><td styleCode="Rrule" align="center" valign="top"> &lt;1 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Dyspepsia </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> 13 </td><td styleCode="Rrule" align="center" valign="top"> 10 </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> 2 </td><td styleCode="Rrule" align="center" valign="top"> &lt;1 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="bold">Musculoskeletal System</content> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" valign="top"> </td><td styleCode="Rrule" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Myalgia </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> - </td><td styleCode="Rrule" align="center" valign="top"> - </td><td styleCode="Rrule" align="center" valign="top"> 5 </td><td styleCode="Rrule" align="center" valign="top"> 3 </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="bold">Nervous System</content> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" valign="top"> </td><td sty

styleCode="bold">Nervous System</content> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" valign="top"> </td><td sty leCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Somnolence </td><td styleCode="Rrule" align="center" valign="top"> 22 </td><td styleCode="Rrule" align="center" valign="top"> 8 </td><td styleCode="Rrule" align="center" valign="top"> 21 </td><td styleCode="Rrule" align="center" valign="top"> 12 </td><td styleCode="Rrule" align="center" valign="top"> 20 </td><td styleCode="Rrule" align="center" valign="top"> 9 </td><td styleCode="Rrule" align="center" valign="top"> 9 </td><td styleCode="Rrule" align="center" valign="top"> 4 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Insomnia </td><td styleCode="Rrule" align="center" valign="top"> 17 </td><td styleCode="Rrule" align="center" valign="top"> 9 </td><td styleCode="Rrule" align="center" valign="top"> 10 </td><td styleCode="Rrule" align="center" valign="top"> 8 </td><td styleCode="Rrule" align="center" valign="top"> 20 </td><td styleCode="Rrule" align="center" valign="top"> 11 </td><td styleCode="Rrule" align="center" valign="top"> 9 </td><td styleCode="Rrule" align="center" valign="top"> 4 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Dizziness </td><td styleCode="Rrule" align="center" valign="top"> 14 </td><td styleCode="Rrule" align="center" valign="top"> 4 </td><td styleCode="Rrule" align="center" valign="top"> 9 </td><td styleCode="Rrule" align="center" valign="top"> 5 </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> 7 </td><td styleCode="Rrule" align="center" valign="top"> 4 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Libido Decreased </td><td styleCode="Rrule" align="center" valign="top"> 7 </td><td styleCode="Rrule" align="center" valign="top"> 3 </td><td styleCode="Rrule" align="center" valign="top"> 8 </td><td styleCode="Rrule" align="center" valign="top"> &lt;1 </td><td styleCode="Rrule" align="center" valign="top"> 9 </td><td styleCode="Rrule" align="center" valign="top"> 4 </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> 1 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Nervousness </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> - </td><td styleCode="Rrule" align="center" valign="top"> - </td><td styleCode="Rrule" align="center" valign="top"> 8 </td><td styleCode="Rrule" align="center" valign="top"> 7 </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Tremor </td><td styleCode="Rrule" align="center" valign="top"> 7 </td><td styleCode="Rrule" align="center" valign="top"> 1 </td><td styleCode="Rrule" align="center" valign="top"> 7 </td><td styleCode="Rrule" align="center" valign="top"> 0 </td><td styleCode="Rrule" align="center" valign="top"> 8 </td><td styleCode="Rrule" align="center" valign="top"> 2 </td><td styleCode="Rrule" align="center" valign="top"> 4 </td><td styleCode="Rrule" align="center" valign="top"> 2 </td></tr><tr styleCo

"top"> 7 </td><td styleCode="Rrule" align="center" valign="top"> 0 </td><td styleCode="Rrule" align="center" valign="top"> 8 </td><td styleCode="Rrule" align="center" valign="top"> 2 </td><td styleCode="Rrule" align="center" valign="top"> 4 </td><td styleCode="Rrule" align="center" valign="top"> 2 </td></tr><tr styleCo de="Botrule"><td styleCode="Lrule Rrule" valign="top"> Anxiety </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> - </td><td styleCode="Rrule" align="center" valign="top"> - </td><td styleCode="Rrule" align="center" valign="top"> 5 </td><td styleCode="Rrule" align="center" valign="top"> 4 </td><td styleCode="Rrule" align="center" valign="top"> 2 </td><td styleCode="Rrule" align="center" valign="top"> 1 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="bold">Respiratory System</content> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Sinusitis </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> - </td><td styleCode="Rrule" align="center" valign="top"> - </td><td styleCode="Rrule" align="center" valign="top"> 8 </td><td styleCode="Rrule" align="center" valign="top"> 5 </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Yawn </td><td styleCode="Rrule" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> 0 </td><td styleCode="Rrule" align="center" valign="top"> - </td><td styleCode="Rrule" align="center" valign="top"> - </td><td styleCode="Rrule" align="center" valign="top"> 3 </td><td styleCode="Rrule" align="center" valign="top"> 0 </td><td styleCode="Rrule" align="center" valign="top"> 2 </td><td styleCode="Rrule" align="center" valign="top"> 0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="bold">Skin and Appendages</content> </td><td styleCode="Rrule" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" valign="top"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Sweating </td><td styleCode="Rrule" align="center" valign="top"> 6 </td><td styleCode="Rrule" align="center" valign="top"> 2 </td><td styleCode="Rrule" align="center" valign="top"> 10 </td><td styleCode="Rrule" align="center" valign="top"> &lt;1 </td><td styleCode="Rrule" align="center" valign="top"> 7 </td><td styleCode="Rrule" align="center" valign="top"> 2 </td><td styleCode="Rrule" align="center" valign="top"> 14 </td><td styleCode="Rrule" align="center" valign="top"> 3 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="bold">Special Senses</content> </td><td styleCode="Rrule" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td st

="center" valign="top"> 14 </td><td styleCode="Rrule" align="center" valign="top"> 3 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="bold">Special Senses</content> </td><td styleCode="Rrule" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td st yleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" valign="top"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Abnormal Vision^a </td><td styleCode="Rrule" align="center" valign="top"> 5 </td><td styleCode="Rrule" align="center" valign="top"> 1 </td><td styleCode="Rrule" align="center" valign="top"> - </td><td styleCode="Rrule" align="center" valign="top"> - </td><td styleCode="Rrule" align="center" valign="top"> 3 </td><td styleCode="Rrule" align="center" valign="top"> &lt;1 </td><td styleCode="Rrule" align="center" valign="top"> 2 </td><td styleCode="Rrule" align="center" valign="top"> 0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="bold">Urogenital System</content> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" valign="top"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Abnormal Ejaculation^b,c </td><td styleCode="Rrule" align="center" valign="top"> 26 </td><td styleCode="Rrule" align="center" valign="top"> 1 </td><td styleCode="Rrule" align="center" valign="top"> 17 </td><td styleCode="Rrule" align="center" valign="top"> 3 </td><td styleCode="Rrule" align="center" valign="top"> 27 </td><td styleCode="Rrule" align="center" valign="top"> 3 </td><td styleCode="Rrule" align="center" valign="top"> 15 </td><td styleCode="Rrule" align="center" valign="top"> 1 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Female Genital Disorder^b,d </td><td styleCode="Rrule" align="center" valign="top"> 10 </td><td styleCode="Rrule" align="center" valign="top"> &lt;1 </td><td styleCode="Rrule" align="center" valign="top"> - </td><td styleCode="Rrule" align="center" valign="top"> - </td><td styleCode="Rrule" align="center" valign="top"> 7 </td><td styleCode="Rrule" align="center" valign="top"> 1 </td><td styleCode="Rrule" align="center" valign="top"> 3 </td><td styleCode="Rrule" align="center" valign="top"> 0 </td></tr><tr><td styleCode="Lrule Rrule" valign="top"> Impotence^b </td><td styleCode="Rrule" align="center" valign="top"> 5 </td><td styleCode="Rrule" align="center" valign="top"> 3 </td><td styleCode="Rrule" align="center" valign="top"> 9 </td><td styleCode="Rrule" align="center" valign="top"> 3 </td><td styleCode="Rrule" align="center" valign="top"> 10 </td><td styleCode="Rrule" align="center" valign="top"> 1 </td><td styleCode="Rrule" align="center" valign="top"> 9 </td><td styleCode="Rrule" align="center" valign="top"> 0 </td></tr></tbody></table>

9 </td><td styleCode="Rrule" align="center" valign="top"> 3 </td><td styleCode="Rrule" align="center" valign="top"> 10 </td><td styleCode="Rrule" align="center" valign="top"> 1 </td><td styleCode="Rrule" align="center" valign="top"> 9 </td><td styleCode="Rrule" align="center" valign="top"> 0 </td></tr></tbody></table> <table cellspacing="0" cellpadding="0" border="0" width="580.4785"><colgroup><col width="26.6582655516096%"/><col width="18.3297055791041%"/><col width="18.3411616450911%"/><col width="18.3182495131172%"/><col width="18.352617711078%"/></colgroup><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule" rowspan="3" valign="middle"> <content styleCode="bold">Body System / Adverse Reaction</content> </td><td styleCode="Rrule" colspan="4" align="center" valign="top"> <content styleCode="bold">% Reporting Adverse Reaction</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="2" align="center" valign="top"> <content styleCode="bold">Continuous Dosing </content> <content styleCode="bold">Studies 8, 9, and 10</content> </td><td styleCode="Rrule" colspan="2" align="center" valign="top"> <content styleCode="bold">Luteal Phase Dosing </content> <content styleCode="bold">Study 11</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" align="center" valign="top"> <content styleCode="bold">Paroxetine Extended-Release Tablets</content><content styleCode="bold"> </content> <content styleCode="bold">(n = 681)</content> <content styleCode="bold">%</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">Placebo</content> <content styleCode="bold">(n = 349)</content> <content styleCode="bold">%</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">Paroxetine Extended-Release Tablets </content><content styleCode="bold"> </content> <content styleCode="bold">(n = 246)</content> <content styleCode="bold">%</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">Placebo </content> <content styleCode="bold">(n = 120)</content> <content styleCode="bold">%</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="bold">Body as a Whole</content> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" valign="top"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Asthenia </td><td styleCode="Rrule" align="center" valign="top"> 17 </td><td styleCode="Rrule" align="center" valign="top"> 6 </td><td styleCode="Rrule" align="center" valign="top"> 15 </td><td styleCode="Rrule" align="center" valign="top"> 4 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Headache </td><td styleCode="Rrule" align="center" valign="top"> 15 </td><td styleCode="Rrule" align="center" valign="top"> 12 </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Infection </td><td styleCode="Rrule" align="center" valign="top"> 6 </td><td styleCode="Rrule" align="center" valign="top"> 4 </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="bold">Digestive System</content> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" valign="top"> </td></tr><tr styleCode="Botrule"><td styl

" valign="top"> <content styleCode="bold">Digestive System</content> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" valign="top"> </td></tr><tr styleCode="Botrule"><td styl eCode="Lrule Rrule" valign="top"> Nausea </td><td styleCode="Rrule" align="center" valign="top"> 17 </td><td styleCode="Rrule" align="center" valign="top"> 7 </td><td styleCode="Rrule" align="center" valign="top"> 18 </td><td styleCode="Rrule" align="center" valign="top"> 2 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Diarrhea </td><td styleCode="Rrule" align="center" valign="top"> 6 </td><td styleCode="Rrule" align="center" valign="top"> 2 </td><td styleCode="Rrule" align="center" valign="top"> 6 </td><td styleCode="Rrule" align="center" valign="top"> 0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Constipation </td><td styleCode="Rrule" align="center" valign="top"> 5 </td><td styleCode="Rrule" align="center" valign="top"> 1 </td><td styleCode="Rrule" align="center" valign="top"> 2 </td><td styleCode="Rrule" align="center" valign="top"> &lt;1 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="bold">Nervous System</content> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" align="center" valign="top"> </td><td styleCode="Rrule" valign="top"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Libido Decreased </td><td styleCode="Rrule" align="center" valign="top"> 12 </td><td styleCode="Rrule" align="center" valign="top"> 5 </td><td styleCode="Rrule" align="center" valign="top"> 9 </td><td styleCode="Rrule" align="center" valign="top"> 6 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Somnolence </td><td styleCode="Rrule" align="center" valign="top"> 9 </td><td styleCode="Rrule" align="center" valign="top"> 2 </td><td styleCode="Rrule" align="center" valign="top"> 3 </td><td styleCode="Rrule" align="center" valign="top"> &lt;1 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Insomnia </td><td styleCode="Rrule" align="center" valign="top"> 8 </td><td styleCode="Rrule" align="center" valign="top"> 2 </td><td styleCode="Rrule" align="center" valign="top"> 7 </td><td styleCode="Rrule" align="center" valign="top"> 3 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Dizziness </td><td styleCode="Rrule" align="center" valign="top"> 7 </td><td styleCode="Rrule" align="center" valign="top"> 3 </td><td styleCode="Rrule" align="center" valign="top"> 6 </td><td styleCode="Rrule" align="center" valign="top"> 3 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Tremor </td><td styleCode="Rrule" align="center" valign="top"> 4 </td><td styleCode="Rrule" align="center" valign="top"> &lt;1 </td><td styleCode="Rrule" align="center" valign="top"> 5 </td><td styleCode="Rrule" align="center" valign="top"> 0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="bold">Skin and Appendages</content> Sweating </td><td styleCode="Rrule" align="center" valign="top"> 7 </td><td styleCode="Rrule" align="center" valign="top"> &lt;1 </td><td styleCode="Rrule" align="center" valign="top"> 6 </td><td styleCode="Rrule" align="center" valign="top"> &lt;1 </td></tr><tr><td styleCode="Lrule Rrule" valign="top"> <content styleCode="bold">Urogenital System </content> <content styleCode="bold"> </content>Female Genital Disorders^c </td><td styleCode="Rrule" align="center" valign="top"> 8 </td><td styleCode="

<td styleCode="Rrule" align="center" valign="top"> &lt;1 </td></tr><tr><td styleCode="Lrule Rrule" valign="top"> <content styleCode="bold">Urogenital System </content> <content styleCode="bold"> </content>Female Genital Disorders^c </td><td styleCode="Rrule" align="center" valign="top"> 8 </td><td styleCode=" Rrule" align="center" valign="top"> 1 </td><td styleCode="Rrule" align="center" valign="top"> 2 </td><td styleCode="Rrule" align="center" valign="top"> 0 </td></tr></tbody></table>

<td styleCode="Rrule" align="center" valign="top"> &lt;1 </td></tr><tr><td styleCode="Lrule Rrule" valign="top"> <content styleCode="bold">Urogenital System </content> <content styleCode="bold"> </content>Female Genital Disorders^c </td><td styleCode="Rrule" align="center" valign="top"> 8 </td><td styleCode=" Rrule" align="center" valign="top"> 1 </td><td styleCode="Rrule" align="center" valign="top"> 2 </td><td styleCode="Rrule" align="center" valign="top"> 0 </td></tr></tbody></table> <table cellspacing="0" cellpadding="0" border="0" width="584.4685"><colgroup><col width="11.7874615997269%"/><col width="9.55740129707589%"/><col width="7.69143247240869%"/><col width="9.98975992718171%"/><col width="7.74832176584367%"/><col width="9.61429059051087%"/><col width="8.12379110251451%"/><col width="9.86460348162476%"/><col width="7.88485607008761%"/><col width="9.79633632950279%"/><col width="7.94174536352258%"/></colgroup><thead><tr><th styleCode="Lrule Rrule Toprule"> </th><th styleCode="Lrule Rrule Toprule" colspan="2" align="center"> <content styleCode="bold">Studies 1 and 2</content> <content styleCode="bold">%</content> </th><th styleCode="Lrule Rrule Toprule" colspan="2" align="center"> <content styleCode="bold">Studies 4, 5, and 6</content> <content styleCode="bold">%</content> </th><th styleCode="Lrule Rrule Toprule" colspan="2" align="center"> <content styleCode="bold">Study 7</content> <content styleCode="bold">%</content> </th><th styleCode="Lrule Rrule Toprule" colspan="2" align="center"> <content styleCode="bold">Studies 8, 9, and 11 </content> <content styleCode="bold">(Continuous Dosing)</content> <content styleCode="bold">%</content> </th><th styleCode="Lrule Rrule Toprule" colspan="2" align="center"> <content styleCode="bold">Study 10 </content> <content styleCode="bold">(Luteal Phase Dosing)</content> <content styleCode="bold">%</content> </th></tr><tr><th styleCode="Lrule Rrule Toprule"> </th><th styleCode="Lrule Rrule Toprule" align="center"> <content styleCode="bold">Paroxetine Extended-Release Tablets</content> </th><th styleCode="Lrule Rrule Toprule" align="center"> <content styleCode="bold">Placebo</content> </th><th styleCode="Lrule Rrule Toprule" align="center"> <content styleCode="bold">Paroxetine Extended-Release Tablets</content> </th><th styleCode="Lrule Rrule Toprule" align="center"> <content styleCode="bold">Placebo</content> </th><th styleCode="Lrule Rrule Toprule" align="center"> <content styleCode="bold">Paroxetine Extended-Release Tablets</content> </th><th styleCode="Lrule Rrule Toprule" align="center"> <content styleCode="bold">Placebo</content> </th><th styleCode="Lrule Rrule Toprule" align="center"> <content styleCode="bold">Paroxetine Extended-Release Tablets</content> </th><th styleCode="Lrule Rrule Toprule" align="center"> <content styleCode="bold">Placebo</content> </th><th styleCode="Lrule Rrule Toprule" align="center"> <content styleCode="bold">Paroxetine Extended-Release Tablets</content> </th><th styleCode="Lrule Rrule Toprule" align="center"> <content styleCode="bold">Placebo</content> </th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="bold">n (males)</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">78</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">78</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">162</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">194</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">88</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">97</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">NA</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">NA</content> </td><t

yleCode="bold">88</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">97</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">NA</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">NA</content> </td><t d styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">NA</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">NA</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Decreased Libido </td><td styleCode="Rrule" align="center" valign="top"> 10 </td><td styleCode="Rrule" align="center" valign="top"> 5 </td><td styleCode="Rrule" align="center" valign="top"> 9 </td><td styleCode="Rrule" align="center" valign="top"> 6 </td><td styleCode="Rrule" align="center" valign="top"> 13 </td><td styleCode="Rrule" align="center" valign="top"> 1 </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Abnormal ejaculation </td><td styleCode="Rrule" align="center" valign="top"> 26 </td><td styleCode="Rrule" align="center" valign="top"> 1 </td><td styleCode="Rrule" align="center" valign="top"> 27 </td><td styleCode="Rrule" align="center" valign="top"> 3 </td><td styleCode="Rrule" align="center" valign="top"> 15 </td><td styleCode="Rrule" align="center" valign="top"> 1 </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Impotence </td><td styleCode="Rrule" align="center" valign="top"> 5 </td><td styleCode="Rrule" align="center" valign="top"> 3 </td><td styleCode="Rrule" align="center" valign="top"> 10 </td><td styleCode="Rrule" align="center" valign="top"> 1% </td><td styleCode="Rrule" align="center" valign="top"> 9 </td><td styleCode="Rrule" align="center" valign="top"> 0 </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td><td styleCode="Rrule" align="center" valign="top"> NA </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="bold">n (females)</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">134</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">133</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">282</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">251</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">98</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">87</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">681</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">349</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">246</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">120</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Decreased Libido </td><td styleCode="Rrule" align="center" valign="top"> 4 </td><td styleCode="Rrule" align="center" valign=

de="bold">246</content> </td><td styleCode="Rrule" align="center" valign="top"> <content styleCode="bold">120</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Decreased Libido </td><td styleCode="Rrule" align="center" valign="top"> 4 </td><td styleCode="Rrule" align="center" valign= "top"> 2 </td><td styleCode="Rrule" align="center" valign="top"> 8 </td><td styleCode="Rrule" align="center" valign="top"> 2 </td><td styleCode="Rrule" align="center" valign="top"> 4 </td><td styleCode="Rrule" align="center" valign="top"> 1 </td><td styleCode="Rrule" align="center" valign="top"> 12 </td><td styleCode="Rrule" align="center" valign="top"> 5 </td><td styleCode="Rrule" align="center" valign="top"> 9 </td><td styleCode="Rrule" align="center" valign="top"> 6 </td></tr><tr><td styleCode="Lrule Rrule" valign="top"> Orgasmic Disturbance </td><td styleCode="Rrule" align="center" valign="top"> 10 </td><td styleCode="Rrule" align="center" valign="top"> &lt;1 </td><td styleCode="Rrule" align="center" valign="top"> 7 </td><td styleCode="Rrule" align="center" valign="top"> 1 </td><td styleCode="Rrule" align="center" valign="top"> 3 </td><td styleCode="Rrule" align="center" valign="top"> 0 </td><td styleCode="Rrule" align="center" valign="top"> 8 </td><td styleCode="Rrule" align="center" valign="top"> 1 </td><td styleCode="Rrule" align="center" valign="top"> 2 </td><td styleCode="Rrule" align="center" valign="top"> 0 </td></tr></tbody></table>

7 DRUG INTERACTIONS • Drugs Highly Bound to Plasma Protein: Monitor for adverse reactions and reduce dosage of paroxetine or other protein-bound drugs (e.g., warfarin) as warranted. (7) • Drugs Metabolized by CYP2D6: Reduce dosage of drugs metabolized by CYP2D6 as warranted. (7) • Concomitant use with Tamoxifen: Consider use of an alternative antidepressant with little or no CYP2D6 inhibition. (5.11, 7) 7.1 Clinically Significant Drug Interactions with Paroxetine Table 6 includes clinically significant drug interactions with paroxetine. Table 6: Clinically Significant Drug Interactions with Paroxetine Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact The concomitant use of SSRIs, including paroxetine, and MAOIs increases the risk of serotonin syndrome. Intervention Paroxetine is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [see Dosage and Administration (2.6), Contraindications (4), Warnings and Precautions (5.2)] . Examples selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue Pimozide and Thioridazine Clinical Impact Increased plasma concentrations of pimozide and thioridazine, drugs with a narrow therapeutic index, may increase the risk of QTc prolongation and ventricular arrhythmias. Intervention Paroxetine is contraindicated in patients taking pimozide or thioridazine [see Contraindications (4)]. Other Serotonergic Drugs Clinical Impact The concomitant use of serotonergic drugs with paroxetine increases the risk of serotonin syndrome. Intervention Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of paroxetine and/or concomitant serotonergic drugs [see Warnings and Precautions (5.2)] . Examples Other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, St. John’s Wort Drugs that Interfere with Hemostasis (antiplatelet agents and anticoagulants) Clinical Impact The concurrent use of an antiplatelet agent or anticoagulant with paroxetine may potentiate the risk of bleeding. Intervention Inform patients of the increased risk of bleeding associated with the concomitant use of paroxetine and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio [see Warnings and Precautions (5.5)] . Examples aspirin, clopidogrel, heparin, warfarin Drugs Highly Bound to Plasma Protein Clinical Impact Paroxetine is highly bound to plasma protein. The concomitant use of paroxetine with another drug that is highly bound to plasma protein may increase free concentrations of paroxetine or other tightly-bound drugs in plasma . Intervention Monitor for adverse reactions and reduce dosage of paroxetine or other protein-bound drugs as warranted. Examples warfarin Drugs Metabolized by CYP2D6 Clinical Impact Paroxetine is a CYP2D6 inhibitor [see Clinical Pharmacology (12.3)]. The concomitant use of paroxetine with a CYP2D6 substrate may increase the exposure of the CYP2D6 substrate. Intervention Decrease the dosage of a CYP2D6 substrate if needed with concomitant paroxetine use. Conversely, an increase in dosage of a CYP2D6 substrate may be needed if paroxetine is discontinued. Examples propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, venlafaxine, risperidone.

of a CYP2D6 substrate if needed with concomitant paroxetine use. Conversely, an increase in dosage of a CYP2D6 substrate may be needed if paroxetine is discontinued. Examples propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, venlafaxine, risperidone. Tamoxifen Clinical Impact Concomitant use of tamoxifen with paroxetine may lead to reduced plasma concentrations of the active metabolite (endoxifen) and reduced efficacy of tamoxifen Intervention Consider use of an alternative antidepressant little or no CYP2D6 inhibition [see Warnings and Precautions (5.11)]. Fosamprenavir/Ritonavir Clinical Impact Co-administration of fosamprenavir/ritonavir with paroxetine significantly decreased plasma levels of paroxetine. Intervention Any dose adjustment should be guided by clinical effect (tolerability and efficacy).

<table cellspacing="0" cellpadding="0" border="0" width="537.32"><colgroup><col width="19.2945544554455%"/><col width="80.7054455445545%"/></colgroup><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="2" valign="top"> <content styleCode="bold">Monoamine Oxidase Inhibitors (MAOIs)</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="italics">Clinical Impact</content> </td><td styleCode="Rrule" align="justify" valign="top"> The concomitant use of SSRIs, including paroxetine, and MAOIs increases the risk of serotonin syndrome. </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="italics">Intervention</content> </td><td styleCode="Rrule" align="justify" valign="top"> Paroxetine is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue <content styleCode="italics">[see Dosage and Administration (2.6), Contraindications (4), Warnings and Precautions (5.2)]</content>. </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="italics">Examples</content> </td><td styleCode="Rrule" align="justify" valign="top"> selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="2" valign="top"> <content styleCode="bold">Pimozide and Thioridazine</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="italics">Clinical Impact</content> </td><td styleCode="Rrule" align="justify" valign="top"> Increased plasma concentrations of pimozide and thioridazine, drugs with a narrow therapeutic index, may increase the risk of QTc prolongation and ventricular arrhythmias. </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="italics">Intervention</content> </td><td styleCode="Rrule" valign="top"> Paroxetine is contraindicated in patients taking pimozide or thioridazine <content styleCode="italics">[see Contraindications (4)].</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="2" valign="top"> <content styleCode="bold">Other Serotonergic Drugs</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="italics">Clinical Impact</content> </td><td styleCode="Rrule" align="justify" valign="top"> The concomitant use of serotonergic drugs with paroxetine increases the risk of serotonin syndrome. </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="italics">Intervention</content> </td><td styleCode="Rrule" align="justify" valign="top"> Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of paroxetine and/or concomitant serotonergic drugs <content styleCode="italics">[see Warnings and Precautions (5.2)]</content>. </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="italics">Examples</content> </td><td styleCode="Rrule" align="justify" valign="top"> Other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, St.

ngs and Precautions (5.2)]</content>. </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="italics">Examples</content> </td><td styleCode="Rrule" align="justify" valign="top"> Other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, St. John&#x2019;s Wort </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="2" valign="top"> <content styleCode="bold">Drugs that Interfere with Hemostasis (antiplatelet agents and anticoagulants)</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="italics">Clinical Impact</content> </td><td styleCode="Rrule" align="justify" valign="top"> The concurrent use of an antiplatelet agent or anticoagulant with paroxetine may potentiate the risk of bleeding. </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="italics">Intervention</content> </td><td styleCode="Rrule" align="justify" valign="top"> Inform patients of the increased risk of bleeding associated with the concomitant use of paroxetine and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio <content styleCode="italics">[see Warnings and Precautions (5.5)]</content>. </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="italics">Examples</content> </td><td styleCode="Rrule" valign="top"> aspirin, clopidogrel, heparin, warfarin </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="2" valign="top"> <content styleCode="bold">Drugs Highly Bound to Plasma Protein</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="italics">Clinical Impact</content> </td><td styleCode="Rrule" align="justify" valign="top"> Paroxetine is highly bound to plasma protein. The concomitant use of paroxetine with another drug that is highly bound to plasma protein may increase free concentrations of paroxetine or other tightly-bound drugs in plasma<content styleCode="italics">.</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="italics">Intervention</content> </td><td styleCode="Rrule" valign="top"> Monitor for adverse reactions and reduce dosage of paroxetine or other protein-bound drugs as warranted. </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="italics">Examples</content> </td><td styleCode="Rrule" valign="top"> warfarin </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="2" valign="top"> <content styleCode="bold">Drugs Metabolized by CYP2D6</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="italics">Clinical Impact</content> </td><td styleCode="Rrule" align="justify" valign="top"> Paroxetine is a CYP2D6 inhibitor <content styleCode="italics">[see Clinical Pharmacology (12.3)]. </content>The concomitant use of paroxetine with a CYP2D6 substrate may increase the exposure of the CYP2D6 substrate. </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="italics">Intervention</content> </td><td styleCode="Rrule" align="justify" valign="top"> Decrease the dosage of a CYP2D6 substrate if needed with concomitant paroxetine use. Conversely, an increase in dosage of a CYP2D6 substrate may be needed if paroxetine is discontinued.

rule Rrule" valign="top"> <content styleCode="italics">Intervention</content> </td><td styleCode="Rrule" align="justify" valign="top"> Decrease the dosage of a CYP2D6 substrate if needed with concomitant paroxetine use. Conversely, an increase in dosage of a CYP2D6 substrate may be needed if paroxetine is discontinued. </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="italics">Examples</content> </td><td styleCode="Rrule" align="justify" valign="top"> propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, venlafaxine, risperidone. </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="2" valign="top"> <content styleCode="bold">Tamoxifen</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="italics">Clinical Impact</content> </td><td styleCode="Rrule" align="justify" valign="top"> Concomitant use of tamoxifen with paroxetine may lead to reduced plasma concentrations of the active metabolite (endoxifen) and reduced efficacy of tamoxifen </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="italics">Intervention</content> </td><td styleCode="Rrule" align="justify" valign="top"> Consider use of an alternative antidepressant little or no CYP2D6 inhibition <content styleCode="italics">[see Warnings and Precautions (5.11)].</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="2" align="justify" valign="top"> <content styleCode="bold">Fosamprenavir/Ritonavir</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> <content styleCode="italics">Clinical Impact</content> </td><td styleCode="Rrule" align="justify" valign="top"> Co-administration of fosamprenavir/ritonavir with paroxetine significantly decreased plasma levels of paroxetine. </td></tr><tr><td styleCode="Lrule Rrule" valign="top"> <content styleCode="italics">Intervention</content> </td><td styleCode="Rrule" align="justify" valign="top"> Any dose adjustment should be guided by clinical effect (tolerability and efficacy). </td></tr></tbody></table>

8 USE IN SPECIFIC POPULATIONS • Pregnancy: SSRI use, particularly later in pregnancy, may increase the risk of persistent pulmonary hypertension and symptoms of poor adaptation (respiratory distress, temperature instability, feeding difficulty, hypotonia, irritability) in the neonate. (5.4, 8.1) • Nursing Mothers: Discontinue drug or nursing taking into consideration importance of drug to mother. (8.3) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/. Risk Summary Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions (5.5) and Clinical Considerations]. Paroxetine is associated with a less than 2-fold increase in cardiovascular malformations when administered to a pregnant woman during the first trimester. While individual epidemiological studies on the association between paroxetine use and cardiovascular malformations have reported inconsistent findings, some meta-analyses of epidemiological studies have identified an increased risk of cardiovascular malformations ( see Data ). There are risks of persistent pulmonary hypertension of the newborn (PPHN) ( see Data ) and/or poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (SSRIs), including paroxetine, during pregnancy. There also are risks associated with untreated depression in pregnancy ( see Clinical Considerations ). For women who intend to become pregnant or who are in their first trimester of pregnancy, paroxetine should be initiated only after consideration of the other available treatment options. No evidence of treatment related malformations was observed in animal reproduction studies, when paroxetine was administered during the period of organogenesis at doses up to 50 mg/kg/day in rats and 6 mg/kg/day in rabbits. These doses are approximately 6 (rat) and less than 2 (rabbit) times the maximum recommended human dose (MRHD – 75 mg) on an mg/m 2 basis. When paroxetine was administered to female rats during the last trimester of gestation and continued through lactation, there was an increase in the number of pup deaths during the first four days of lactation. This effect occurred at a dose of 1 mg/kg/day which is less than the MRHD on an mg/m 2 basis ( see Data ). The estimated background risks of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants.

iscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants. This finding is from a prospective longitudinal study of 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. Consider the risks of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. Maternal Adverse Reactions Use of paroxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions (5.5)]. Fetal/Neonatal adverse reactions Neonates exposed to paroxetine and other SSRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremors, jitteriness, irritability, and constant crying. These findings are consistent with either a direct toxic effect of SSRIs or possibly a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see Warnings and Precautions (5.4)] . Data Human Data Published epidemiological studies on the association between first trimester paroxetine use and cardiovascular malformations have reported inconsistent results; however, meta-analyses of population-based cohort studies published between 1996-2017 indicate a less than 2-fold increased risk for overall cardiovascular malformations. Specific cardiac malformations identified in two meta-analyses include approximately 2 to 2.5-fold increased risk for right ventricular outflow tract defects. One meta-analysis also identified an increased risk (less than 2-fold) for bulbus cordis anomalies and anomalies of cardiac septal closure, and an increased risk for atrial septal defects (pooled OR 2.38, 95% CI 1.14-4.97). Important limitations of the studies included in these meta-analyses include potential confounding by indication, depression severity, and potential exposure misclassification. Exposure to SSRIs, particularly later in pregnancy, may have an increased risk for PPHN. PPHN occurs in 1-2 per 1000 live births in the general population and is associated with substantial neonatal morbidity and mortality. Animal Data Reproduction studies were performed at doses up to 50 mg/kg/day in rats and 6 mg/kg/day in rabbits administered during organogenesis. These doses are approximately 6 (rat) and less than 2 (rabbit) times the maximum recommended human dose (MRHD – 75 mg) on an mg/m 2 basis. These studies have revealed no evidence of malformations. However, in rats, there was an increase in pup deaths during the first 4 days of lactation when dosing occurred during the last trimester of gestation and continued throughout lactation. This effect occurred at a dose of 1 mg/kg/day which is less than the MRHD on an mg/m 2 basis. The no-effect dose for rat pup mortality was not determined. The cause of these deaths is not known. 8.2 Lactation Risk Summary Data from the published literature report the presence of paroxetine in human milk ( see Data ). There are reports of agitation, irritability, poor feeding and poor weight gain in infants exposed to paroxetine through breast milk ( see Clinical Considerations ).

of these deaths is not known. 8.2 Lactation Risk Summary Data from the published literature report the presence of paroxetine in human milk ( see Data ). There are reports of agitation, irritability, poor feeding and poor weight gain in infants exposed to paroxetine through breast milk ( see Clinical Considerations ). There are no data on the effects of paroxetine on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for paroxetine and any potential adverse effects on the breastfed infant from paroxetine or the underlying maternal condition. Clinical Considerations Infants exposed to paroxetine should be monitored for agitation, irritability, poor feeding and poor weight gain. Data Published literature suggests the presence of paroxetine in human milk with relative infant doses ranging between 0.4% to 2.2%, and a milk: plasma ratio of <1. No significant amounts were detected in the plasma of infants after breastfeeding. 8.3 Females and Males of Reproductive Potential Infertility Male Based on findings from clinical studies, paroxetine may affect sperm quality which may impair fertility; it is not known if this effect is reversible [see Nonclinical Toxicology (13.1)]. 8.4 Pediatric Use The safety and effectiveness of paroxetine in pediatric patients have not been established [see Boxed Warning, Warnings and Precautions (5.1)] . Three placebo-controlled trials in 752 pediatric patients with MDD have been conducted with immediate-release paroxetine, and effectiveness was not established in pediatric patients. Decreased appetite and weight loss have been observed in association with the use of SSRIs. In placebo-controlled clinical trials conducted with pediatric patients, the following adverse reactions were reported in at least 2% of pediatric patients treated with immediate-release paroxetine hydrochloride and at a rate at least twice that for pediatric patients receiving placebo: emotional lability (including self-harm, suicidal thoughts, attempted suicide, crying, and mood fluctuations), hostility, decreased appetite, tremor, sweating, hyperkinesia, and agitation. Adverse reactions upon discontinuation of treatment with immediate-release paroxetine hydrochloride in the pediatric clinical trials that included a taper phase regimen, which occurred in at least 2% of patients and at a rate at least twice that of placebo, were: emotional lability (including suicidal ideation, suicide attempt, mood changes, and tearfulness), nervousness, dizziness, nausea, and abdominal pain. 8.5 Geriatric Use SSRIs and SNRIs, including paroxetine, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [see Warnings and Precautions (5.9)]. In premarketing clinical trials with immediate-release paroxetine hydrochloride, 17% of paroxetine treated patients (approximately 700) were 65 years or older. Pharmacokinetic studies revealed a decreased clearance in the elderly, and a lower starting dose is recommended; however, no overall differences in safety or effectiveness were observed between these subjects and younger subjects [see Dosage and Administration (2.5), Clinical Pharmacology (12.3)] 8.6 Renal and/or Hepatic Impairment Increased plasma concentrations of paroxetine occur in patients with renal and hepatic impairment. The initial dosage of paroxetine should be reduced in patients with severe renal impairment and patients with severe hepatic impairment [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3)] .

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/. Risk Summary Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions (5.5) and Clinical Considerations]. Paroxetine is associated with a less than 2-fold increase in cardiovascular malformations when administered to a pregnant woman during the first trimester. While individual epidemiological studies on the association between paroxetine use and cardiovascular malformations have reported inconsistent findings, some meta-analyses of epidemiological studies have identified an increased risk of cardiovascular malformations ( see Data ). There are risks of persistent pulmonary hypertension of the newborn (PPHN) ( see Data ) and/or poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (SSRIs), including paroxetine, during pregnancy. There also are risks associated with untreated depression in pregnancy ( see Clinical Considerations ). For women who intend to become pregnant or who are in their first trimester of pregnancy, paroxetine should be initiated only after consideration of the other available treatment options. No evidence of treatment related malformations was observed in animal reproduction studies, when paroxetine was administered during the period of organogenesis at doses up to 50 mg/kg/day in rats and 6 mg/kg/day in rabbits. These doses are approximately 6 (rat) and less than 2 (rabbit) times the maximum recommended human dose (MRHD – 75 mg) on an mg/m 2 basis. When paroxetine was administered to female rats during the last trimester of gestation and continued through lactation, there was an increase in the number of pup deaths during the first four days of lactation. This effect occurred at a dose of 1 mg/kg/day which is less than the MRHD on an mg/m 2 basis ( see Data ). The estimated background risks of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants. This finding is from a prospective longitudinal study of 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. Consider the risks of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. Maternal Adverse Reactions Use of paroxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions (5.5)].

der the risks of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. Maternal Adverse Reactions Use of paroxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions (5.5)]. Fetal/Neonatal adverse reactions Neonates exposed to paroxetine and other SSRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremors, jitteriness, irritability, and constant crying. These findings are consistent with either a direct toxic effect of SSRIs or possibly a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see Warnings and Precautions (5.4)] . Data Human Data Published epidemiological studies on the association between first trimester paroxetine use and cardiovascular malformations have reported inconsistent results; however, meta-analyses of population-based cohort studies published between 1996-2017 indicate a less than 2-fold increased risk for overall cardiovascular malformations. Specific cardiac malformations identified in two meta-analyses include approximately 2 to 2.5-fold increased risk for right ventricular outflow tract defects. One meta-analysis also identified an increased risk (less than 2-fold) for bulbus cordis anomalies and anomalies of cardiac septal closure, and an increased risk for atrial septal defects (pooled OR 2.38, 95% CI 1.14-4.97). Important limitations of the studies included in these meta-analyses include potential confounding by indication, depression severity, and potential exposure misclassification. Exposure to SSRIs, particularly later in pregnancy, may have an increased risk for PPHN. PPHN occurs in 1-2 per 1000 live births in the general population and is associated with substantial neonatal morbidity and mortality. Animal Data Reproduction studies were performed at doses up to 50 mg/kg/day in rats and 6 mg/kg/day in rabbits administered during organogenesis. These doses are approximately 6 (rat) and less than 2 (rabbit) times the maximum recommended human dose (MRHD – 75 mg) on an mg/m 2 basis. These studies have revealed no evidence of malformations. However, in rats, there was an increase in pup deaths during the first 4 days of lactation when dosing occurred during the last trimester of gestation and continued throughout lactation. This effect occurred at a dose of 1 mg/kg/day which is less than the MRHD on an mg/m 2 basis. The no-effect dose for rat pup mortality was not determined. The cause of these deaths is not known.

8.4 Pediatric Use The safety and effectiveness of paroxetine in pediatric patients have not been established [see Boxed Warning, Warnings and Precautions (5.1)] . Three placebo-controlled trials in 752 pediatric patients with MDD have been conducted with immediate-release paroxetine, and effectiveness was not established in pediatric patients. Decreased appetite and weight loss have been observed in association with the use of SSRIs. In placebo-controlled clinical trials conducted with pediatric patients, the following adverse reactions were reported in at least 2% of pediatric patients treated with immediate-release paroxetine hydrochloride and at a rate at least twice that for pediatric patients receiving placebo: emotional lability (including self-harm, suicidal thoughts, attempted suicide, crying, and mood fluctuations), hostility, decreased appetite, tremor, sweating, hyperkinesia, and agitation. Adverse reactions upon discontinuation of treatment with immediate-release paroxetine hydrochloride in the pediatric clinical trials that included a taper phase regimen, which occurred in at least 2% of patients and at a rate at least twice that of placebo, were: emotional lability (including suicidal ideation, suicide attempt, mood changes, and tearfulness), nervousness, dizziness, nausea, and abdominal pain.

8.5 Geriatric Use SSRIs and SNRIs, including paroxetine, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [see Warnings and Precautions (5.9)]. In premarketing clinical trials with immediate-release paroxetine hydrochloride, 17% of paroxetine treated patients (approximately 700) were 65 years or older. Pharmacokinetic studies revealed a decreased clearance in the elderly, and a lower starting dose is recommended; however, no overall differences in safety or effectiveness were observed between these subjects and younger subjects [see Dosage and Administration (2.5), Clinical Pharmacology (12.3)]

10 OVERDOSAGE The following have been reported with paroxetine tablet overdosage: • Seizures, which may be delayed, and altered mental status including coma. • Cardiovascular toxicity, which may be delayed, including QRS and QTc interval prolongation. Hypertension most commonly seen, but rarely can see hypotension alone or with co-ingestants including alcohol. • Serotonin syndrome (patients with a multiple drug overdosage with other proserotonergic drugs may have a higher risk). Gastrointestinal decontamination with activated charcoal should be considered in patients who present early after a paroxetine overdose. Consider contacting a Poison Center (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations.

11 DESCRIPTION Paroxetine extended-release tablets USP, contains paroxetine hydrochloride, USP an SSRI. It is the hydrochloride salt of a phenylpiperidine compound identified chemically as (-)- trans -4R-(4’-fluorophenyl)-3S-[(3’,4’­ methylenedioxyphenoxy) methyl] piperidine hydrochloride hemihydrate and has the empirical formula of C 19 H 20 FNO 3 •HCl•1/2H 2 O. The molecular weight is 374.8 g/mol (329.4 g/mol as free base). The structural formula of paroxetine hydrochloride, USP is: Paroxetine hydrochloride, USP is white or almost white crystalline powder, having a melting point range of 120 o C to 138 o C and soluble in methanol and in alcohol, slightly soluble in water. Paroxetine extended-release tablets, USP are intended for oral administration. Each extended-release tablet contains 12.5 mg, 25 mg or 37.5 mg paroxetine equivalent to 14.22 mg, 28.51 mg or 42.76 mg of paroxetine hydrochloride USP, respectively. Each tablet consists of a hydrophilic matrix that contains the active material. Inactive ingredients consist of colloidal silicon dioxide, glyceryl dibehenate, hypromellose, lactose monohydrate, magnesium stearate, methacrylic acid copolymer, povidone K-30, talc and triethyl citrate. The film-coating material contains hypromellose, polyethylene glycol 400, polyethylene glycol 6000 and titanium dioxide. Additionally, 12.5 mg tablets contain D&C Yellow No. 10 Lake, FD&C Yellow No. 6 Aluminium Lake and polysorbate 80, 25 mg tablets contain D&C Red No. 30 Lake and polysorbate 80 and 37.5 mg tablets contain FD&C Blue No. 2 Aluminium Lake and talc. FDA approved dissolution test specifications differ from USP. paroxetine-str.jpg

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The mechanism of action of paroxetine in the treatment of major depressive disorder (MDD), panic disorder (PD), social anxiety disorder (SAD), and premenstrual dysphoric disorder (PMDD) is unknown, but is presumed to be linked to potentiation of serotonergic activity in the central nervous system resulting from inhibition of neuronal reuptake of serotonin (5-HT). 12.2 Pharmacodynamics Studies at clinically relevant doses in humans have demonstrated that paroxetine blocks the uptake of serotonin into human platelets. In vitro studies in animals also suggest that paroxetine is a potent and highly selective inhibitor of neuronal serotonin reuptake (SSRI) and has only very weak effects on norepinephrine and dopamine neuronal reuptake. 12.3 Pharmacokinetics Absorption Tablets of paroxetine extended-release tablets contain a degradable polymeric matrix designed to control the dissolution rate of paroxetine over a period of approximately 4 to 5 hours. In addition to controlling the rate of drug release in vivo , an enteric coat delays the start of drug release until tablets of paroxetine extended-release tablets have left the stomach. Paroxetine extended-release tablets are completely absorbed after oral dosing of a solution of the hydrochloride salt. In a study in which normal male and female subjects (n = 23) received single oral doses of paroxetine extended-release tablets at 4 dosage strengths (12.5 mg, 25 mg, 37.5 mg, and 50 mg), paroxetine extended-release tablets C max and AUC 0-inf increased disproportionately with dose (as seen also with immediate-release formulations). Mean C max and AUC 0-inf values at these doses were 2, 5.5, 9, and 12.5 ng/mL, and 121, 261, 338, and 540 ng•hr./mL, respectively. T max was observed typically between 6 and 10 hours post-dose, reflecting a reduction in absorption rate compared with immediate-release formulations. The bioavailability of 25 mg paroxetine extended-release tablets are not affected by food. Distribution Paroxetine distributes throughout the body, including the CNS, with only 1% remaining in the plasma. Approximately 95% and 93% of paroxetine is bound to plasma protein at 100 ng/mL and 400 ng/mL, respectively. Under clinical conditions, paroxetine concentrations would normally be less than 400 ng/mL. Paroxetine does not alter the in vitro protein binding of phenytoin or warfarin. Elimination Metabolism The mean elimination half-life of paroxetine was 15 to 20 hours throughout a range of single doses of paroxetine extended-release tablets (12.5 mg, 25 mg, 37.5 mg, and 50 mg). During repeated administration of paroxetine extended-release tablets (25 mg once daily), steady state was reached within 2 weeks (i.e., comparable to immediate-release formulations). In a repeat-dose study in which normal male and female subjects (n = 23) received paroxetine extended-release tablets (25 mg daily), mean steady state C max , C min , and AUC 0-24 values were 30 ng/mL, 20 ng/mL, and 550 ng•hr./mL, respectively. Based on studies using immediate-release formulations, steady-state drug exposure based on AUC 0-24 was several-fold greater than would have been predicted from single-dose data. The excess accumulation is a consequence of the fact that 1 of the enzymes that metabolizes paroxetine is readily saturable.

L, respectively. Based on studies using immediate-release formulations, steady-state drug exposure based on AUC 0-24 was several-fold greater than would have been predicted from single-dose data. The excess accumulation is a consequence of the fact that 1 of the enzymes that metabolizes paroxetine is readily saturable. In steady-state dose proportionality studies involving elderly and nonelderly patients, at doses of the immediate-release formulation of 20 mg to 40 mg daily for the elderly and 20 mg to 50 mg daily for the nonelderly, some nonlinearity was observed in both populations, again reflecting a saturable metabolic pathway (Figure 3). Paroxetine is extensively metabolized after oral administration. The principal metabolites are polar and conjugated products of oxidation and methylation, which are readily cleared. Conjugates with glucuronic acid and sulfate predominate, and major metabolites have been isolated and identified. Data indicate that the metabolites have no more than 1/50 the potency of the parent compound at inhibiting serotonin uptake. The metabolism of paroxetine is accomplished in part by CYP2D6. Saturation of this enzyme at clinical doses appears to account for the nonlinearity of paroxetine kinetics with increasing dose and increasing duration of treatment. The role of this enzyme in paroxetine metabolism also suggests potential drug-drug interactions [see Drug Interactions (7.3)]. Excretion Approximately 64% of a 30-mg oral solution dose of paroxetine was excreted in the urine with 2% as the parent compound and 62% as metabolites over a 10-day post-dosing period. About 36% was excreted in the feces (probably via the bile), mostly as metabolites and less than 1% as the parent compound over the 10-day post-dosing period. The elimination half-life is approximately 15 to 20 hours after a single dose of paroxetine extended-release tablets. Paroxetine metabolism is mediated in part by CYP2D6, and the metabolites are primarily excreted in the urine and to some extent in the feces. Pharmacokinetic behavior of paroxetine has not been evaluated in subjects who are deficient in CYP2D6 (poor metabolizers). Drug Interaction Studies There are clinically significant, known drug interactions between paroxetine and other drugs [see Drug Interactions (7)]. Figure 1: Impact of Paroxetine on the Pharmacokinetics of Co-Administered Drugs (log scale) Figure 2: Impact of Co-Administered Drugs on the Pharmacokinetics of Paroxetine Theophylline: Reports of elevated theophylline levels associated with immediate-release paroxetine treatment have been reported. While this interaction has not been formally studied, it is recommended that theophylline levels be monitored when these drugs are concurrently administered. Drugs Metabolized by Cytochrome CYP3A4 An in vivo interaction study involving the coadministration under steady-state conditions of paroxetine and terfenadine, a substrate for CYP3A4, revealed no effect of paroxetine on terfenadine pharmacokinetics. In addition, in vitro studies have shown ketoconazole, a potent inhibitor of CYP3A4 activity, to be at least 100 times more potent than paroxetine as an inhibitor of the metabolism of several substrates for this enzyme, including terfenadine, astemizole, cisapride, triazolam, and cyclosporine. Paroxetine’s extent of inhibition of CYP3A4 activity is not expected to be of clinical significance. Specific Populations The impact of specific populations on the pharmacokinetics of paroxetine are shown in Figure 3. Figure 3: Impact of Specific Population on the Pharmacokinetics of Paroxetine (log scale) paroxetine-fig1.jpg paroxetine-fig2.jpg paroxetine-fig3.jpg

12.1 Mechanism of Action The mechanism of action of paroxetine in the treatment of major depressive disorder (MDD), panic disorder (PD), social anxiety disorder (SAD), and premenstrual dysphoric disorder (PMDD) is unknown, but is presumed to be linked to potentiation of serotonergic activity in the central nervous system resulting from inhibition of neuronal reuptake of serotonin (5-HT).

12.3 Pharmacokinetics Absorption Tablets of paroxetine extended-release tablets contain a degradable polymeric matrix designed to control the dissolution rate of paroxetine over a period of approximately 4 to 5 hours. In addition to controlling the rate of drug release in vivo , an enteric coat delays the start of drug release until tablets of paroxetine extended-release tablets have left the stomach. Paroxetine extended-release tablets are completely absorbed after oral dosing of a solution of the hydrochloride salt. In a study in which normal male and female subjects (n = 23) received single oral doses of paroxetine extended-release tablets at 4 dosage strengths (12.5 mg, 25 mg, 37.5 mg, and 50 mg), paroxetine extended-release tablets C max and AUC 0-inf increased disproportionately with dose (as seen also with immediate-release formulations). Mean C max and AUC 0-inf values at these doses were 2, 5.5, 9, and 12.5 ng/mL, and 121, 261, 338, and 540 ng•hr./mL, respectively. T max was observed typically between 6 and 10 hours post-dose, reflecting a reduction in absorption rate compared with immediate-release formulations. The bioavailability of 25 mg paroxetine extended-release tablets are not affected by food. Distribution Paroxetine distributes throughout the body, including the CNS, with only 1% remaining in the plasma. Approximately 95% and 93% of paroxetine is bound to plasma protein at 100 ng/mL and 400 ng/mL, respectively. Under clinical conditions, paroxetine concentrations would normally be less than 400 ng/mL. Paroxetine does not alter the in vitro protein binding of phenytoin or warfarin. Elimination Metabolism The mean elimination half-life of paroxetine was 15 to 20 hours throughout a range of single doses of paroxetine extended-release tablets (12.5 mg, 25 mg, 37.5 mg, and 50 mg). During repeated administration of paroxetine extended-release tablets (25 mg once daily), steady state was reached within 2 weeks (i.e., comparable to immediate-release formulations). In a repeat-dose study in which normal male and female subjects (n = 23) received paroxetine extended-release tablets (25 mg daily), mean steady state C max , C min , and AUC 0-24 values were 30 ng/mL, 20 ng/mL, and 550 ng•hr./mL, respectively. Based on studies using immediate-release formulations, steady-state drug exposure based on AUC 0-24 was several-fold greater than would have been predicted from single-dose data. The excess accumulation is a consequence of the fact that 1 of the enzymes that metabolizes paroxetine is readily saturable. In steady-state dose proportionality studies involving elderly and nonelderly patients, at doses of the immediate-release formulation of 20 mg to 40 mg daily for the elderly and 20 mg to 50 mg daily for the nonelderly, some nonlinearity was observed in both populations, again reflecting a saturable metabolic pathway (Figure 3). Paroxetine is extensively metabolized after oral administration. The principal metabolites are polar and conjugated products of oxidation and methylation, which are readily cleared. Conjugates with glucuronic acid and sulfate predominate, and major metabolites have been isolated and identified. Data indicate that the metabolites have no more than 1/50 the potency of the parent compound at inhibiting serotonin uptake. The metabolism of paroxetine is accomplished in part by CYP2D6.

readily cleared. Conjugates with glucuronic acid and sulfate predominate, and major metabolites have been isolated and identified. Data indicate that the metabolites have no more than 1/50 the potency of the parent compound at inhibiting serotonin uptake. The metabolism of paroxetine is accomplished in part by CYP2D6. Saturation of this enzyme at clinical doses appears to account for the nonlinearity of paroxetine kinetics with increasing dose and increasing duration of treatment. The role of this enzyme in paroxetine metabolism also suggests potential drug-drug interactions [see Drug Interactions (7.3)]. Excretion Approximately 64% of a 30-mg oral solution dose of paroxetine was excreted in the urine with 2% as the parent compound and 62% as metabolites over a 10-day post-dosing period. About 36% was excreted in the feces (probably via the bile), mostly as metabolites and less than 1% as the parent compound over the 10-day post-dosing period. The elimination half-life is approximately 15 to 20 hours after a single dose of paroxetine extended-release tablets. Paroxetine metabolism is mediated in part by CYP2D6, and the metabolites are primarily excreted in the urine and to some extent in the feces. Pharmacokinetic behavior of paroxetine has not been evaluated in subjects who are deficient in CYP2D6 (poor metabolizers). Drug Interaction Studies There are clinically significant, known drug interactions between paroxetine and other drugs [see Drug Interactions (7)]. Figure 1: Impact of Paroxetine on the Pharmacokinetics of Co-Administered Drugs (log scale) Figure 2: Impact of Co-Administered Drugs on the Pharmacokinetics of Paroxetine Theophylline: Reports of elevated theophylline levels associated with immediate-release paroxetine treatment have been reported. While this interaction has not been formally studied, it is recommended that theophylline levels be monitored when these drugs are concurrently administered. Drugs Metabolized by Cytochrome CYP3A4 An in vivo interaction study involving the coadministration under steady-state conditions of paroxetine and terfenadine, a substrate for CYP3A4, revealed no effect of paroxetine on terfenadine pharmacokinetics. In addition, in vitro studies have shown ketoconazole, a potent inhibitor of CYP3A4 activity, to be at least 100 times more potent than paroxetine as an inhibitor of the metabolism of several substrates for this enzyme, including terfenadine, astemizole, cisapride, triazolam, and cyclosporine. Paroxetine’s extent of inhibition of CYP3A4 activity is not expected to be of clinical significance. Specific Populations The impact of specific populations on the pharmacokinetics of paroxetine are shown in Figure 3. Figure 3: Impact of Specific Population on the Pharmacokinetics of Paroxetine (log scale) paroxetine-fig1.jpg paroxetine-fig2.jpg paroxetine-fig3.jpg

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Two-year carcinogenicity studies were conducted in rodents given paroxetine in the diet at 1, 5, and 25 mg/kg/day (mice) and 1, 5, and 20 mg/kg/day (rats). These doses are up to approximately 1.6 (mouse) and 2.5 (rat) times the MRHD on an mg/m 2 basis. There was a significantly greater number of male rats in the high-dose group with reticulum cell sarcomas (1/100, 0/50, 0/50, and 4/50 for control, low-, middle-, and high-dose groups, respectively) and a significantly increased linear trend across dose groups for the occurrence of lymphoreticular tumors in male rats. Female rats were not affected. Although there was a dose-related increase in the number of tumors in mice, there was no drug-related increase in the number of mice with tumors. The relevance of these findings to humans is unknown. Mutagenesis Paroxetine produced no genotoxic effects in a battery of 5 in vitro and 2 in vivo assays that included the following: Bacterial mutation assay, mouse lymphoma mutation assay, unscheduled DNA synthesis assay, and tests for cytogenetic aberrations in vivo in mouse bone marrow and in vitro in human lymphocytes and in a dominant lethal test in rats. Impairment of Fertility A reduced pregnancy rate was found in reproduction studies in rats at a dose of paroxetine of 15 mg/kg/day, which is approximately twice the MRHD on an mg/m 2 basis. Irreversible lesions occurred in the reproductive tract of male rats after dosing in toxicity studies for 2 to 52 weeks. These lesions consisted of vacuolation of epididymal tubular epithelium at 50 mg/kg/day and atrophic changes in the seminiferous tubules of the testes with arrested spermatogenesis at 25 mg/kg/day (approximately 6 and 3 times the MRHD on an mg/m 2 basis).

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Two-year carcinogenicity studies were conducted in rodents given paroxetine in the diet at 1, 5, and 25 mg/kg/day (mice) and 1, 5, and 20 mg/kg/day (rats). These doses are up to approximately 1.6 (mouse) and 2.5 (rat) times the MRHD on an mg/m 2 basis. There was a significantly greater number of male rats in the high-dose group with reticulum cell sarcomas (1/100, 0/50, 0/50, and 4/50 for control, low-, middle-, and high-dose groups, respectively) and a significantly increased linear trend across dose groups for the occurrence of lymphoreticular tumors in male rats. Female rats were not affected. Although there was a dose-related increase in the number of tumors in mice, there was no drug-related increase in the number of mice with tumors. The relevance of these findings to humans is unknown. Mutagenesis Paroxetine produced no genotoxic effects in a battery of 5 in vitro and 2 in vivo assays that included the following: Bacterial mutation assay, mouse lymphoma mutation assay, unscheduled DNA synthesis assay, and tests for cytogenetic aberrations in vivo in mouse bone marrow and in vitro in human lymphocytes and in a dominant lethal test in rats. Impairment of Fertility A reduced pregnancy rate was found in reproduction studies in rats at a dose of paroxetine of 15 mg/kg/day, which is approximately twice the MRHD on an mg/m 2 basis. Irreversible lesions occurred in the reproductive tract of male rats after dosing in toxicity studies for 2 to 52 weeks. These lesions consisted of vacuolation of epididymal tubular epithelium at 50 mg/kg/day and atrophic changes in the seminiferous tubules of the testes with arrested spermatogenesis at 25 mg/kg/day (approximately 6 and 3 times the MRHD on an mg/m 2 basis).

14 CLINICAL STUDIES 14.1 Major Depressive Disorder The efficacy of paroxetine extended-release tablets as a treatment for major depressive disorder (MDD) was established in two 12-week, multicenter, randomized, double-blind, placebo-controlled, flexible dose studies with paroxetine extended-release tablets (Study 1 and Study 2) in adult patients who met Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria for MDD. Study 1 and 2 included patients 18 to 65 years old who received paroxetine extended-release tablets doses of 25 to 62.5 mg/day (N=212) or placebo (N=211) once daily compared to immediate-release paroxetine 20 to 50 mg (N=217). A third 12-week, multicenter, randomized, double-blind, placebo-controlled, flexible dose study with paroxetine extended-release tablets (Study 3) included elderly patients, ranging in age from 60 to 88 years old and used paroxetine extended-release tablets doses of 12.5 to 50 mg/day (N=104) or placebo (N=109) once daily compared to immediate-release paroxetine 10 to 40 mg (N=106). In all three studies, paroxetine extended-release tablets was statistically superior to placebo in improving depressive symptoms as measured by the following: the mean change from baseline in the Hamilton Depression Rating Scale (HDRS) total score at Week 12, the mean change from baseline in the Hamilton Depressed Mood item score at Week 12, and the mean change from baseline in the Clinical Global Impression (CGI)–Severity of Illness score. Long-term efficacy of paroxetine for treatment of MDD in outpatients was established with one randomized withdrawal study with immediate-release paroxetine. Patients who responded to immediate-release paroxetine (HDRS total score <8) during an initial 8-week open-label treatment phase were then randomized to continue immediate-release paroxetine or placebo, for up to 1 year. Patients treated with immediate-release paroxetine demonstrated a statistically significant lower relapse rate during the withdrawal phase (15%) compared to those on placebo (39%). Effectiveness was similar for male and female patients. 14.2 Panic Disorder The effectiveness of paroxetine extended-release tablets in the treatment of panic disorder (PD) was evaluated in three 10-week, multicenter, flexible-dose studies (Studies 4, 5, and 6) comparing paroxetine extended-release tablets (12.5 to 75 mg daily) to placebo in adult outpatients 19 to 72 years of age who met panic disorder (with or without agoraphobia) criteria according to DSM-IV. These trials were assessed on the basis of their outcomes on 3 variables: (1) the proportions of patients free of full panic attacks at Week 10; (2) change from baseline to Week 10 in the median number of full panic attacks; and (3) change from baseline to Week 10 in the median Clinical Global Impression Severity score. For Studies 4 and 5, paroxetine extended-release tablets were superior to placebo on 2 of these 3 variables. Study 6 failed to consistently demonstrate a statistically significant difference between paroxetine extended-release tablets and placebo on any of these variables. For all 3 studies, the mean dose of paroxetine extended-release tablets for completers at Week 10 was approximately 50 mg/day. Subgroup analyses did not indicate that there were any differences in treatment outcomes as a function of age or gender.

roxetine extended-release tablets and placebo on any of these variables. For all 3 studies, the mean dose of paroxetine extended-release tablets for completers at Week 10 was approximately 50 mg/day. Subgroup analyses did not indicate that there were any differences in treatment outcomes as a function of age or gender. Long-term maintenance effects of paroxetine in patients with PD were demonstrated in a randomized-withdrawal study using immediate-release paroxetine. Patients who were responders during a 10-week, double-blind trial (followed by a 3-month double-blind maintenance phase) of immediate-release paroxetine were re-randomized to continue immediate-release paroxetine or placebo in a 3-month, double-blind withdrawal phase. Patients randomized to immediate-release paroxetine were statistically significantly less likely to relapse than placebo-treated patients. 14.3 Social Anxiety Disorder The efficacy of paroxetine extended-release tablets as a treatment for social anxiety disorder (SAD) was established, in part, on the basis of extrapolation from the established effectiveness of immediate-release paroxetine in the treatment of SAD. In addition, the effectiveness of paroxetine extended-release tablets in the treatment of SAD was demonstrated in one 12-week, multicenter, double-blind, flexible-dose, placebo-controlled study of adult outpatients with a primary diagnosis of SAD by DSM-IV criteria (Study 7). In Study 7, the effectiveness of paroxetine extended-release tablets (12.5 to 37.5 mg daily) compared to placebo was evaluated on the basis of (1) change from baseline in the Liebowitz Social Anxiety Scale (LSAS) total score at Week 12 and (2) the proportion of responders who scored 1 or 2 (very much improved or much improved) on the CGI Global Improvement score at Week 12. In Study 7, paroxetine extended-release tablets demonstrated statistically significant superiority over placebo on both the change on LSAS total score at Week 12 and the CGI Improvement responder criterion at Week 12. For patients who completed the trial, 64% of patients treated with paroxetine extended-release tablets compared to 35% of patients treated with placebo were CGI Improvement responders at Week 12. Subgroup analyses did not indicate that there were any differences in treatment outcomes as a function of gender. Subgroup analyses of studies utilizing the immediate-release formulation of paroxetine generally did not indicate differences in treatment outcomes as a function of age, race, or gender. 14.4 Premenstrual Dysphoric Disorder The effectiveness of paroxetine extended-release tablets for the treatment of Premenstrual Dysphoric Disorder (PMDD) utilizing a continuous dosing regimen has been established in 2 placebo-controlled trials in female patients ages 18 to 46 (Studies 8 and 9 [N=672]). Patients in these trials met DSM-IV criteria for PMDD. Of 1,030 patients including Study 10, who were treated with daily doses of paroxetine extended-release tablets 12.5 or 25 mg/day, or placebo continuously throughout the menstrual cycle for a period of 3 menstrual cycles, the mean duration of the PMDD symptoms was approximately 11 ± 7 years. Patients on systemic hormonal contraceptives were excluded from these trials. Therefore, the efficacy of paroxetine extended-release tablets in combination with systemic (including oral) hormonal contraceptives for the continuous daily treatment of PMDD is unknown. The VAS score is a patient-rated instrument that mirrors the diagnostic criteria of PMDD as identified in the DSM-IV, and includes assessments for mood, physical symptoms, and other symptoms associated with PMDD.

th systemic (including oral) hormonal contraceptives for the continuous daily treatment of PMDD is unknown. The VAS score is a patient-rated instrument that mirrors the diagnostic criteria of PMDD as identified in the DSM-IV, and includes assessments for mood, physical symptoms, and other symptoms associated with PMDD. In Studies 8 and 9, 12.5 mg/day and 25 mg/day of paroxetine extended-release tablets were statistically significantly more effective than placebo as measured by change from baseline to Month 3 on the luteal phase VAS score. In an additional study employing luteal phase dosing (Study 11), patients (N = 366) were treated for the 2 weeks prior to the onset of menses with 12.5 or 25 mg/day of paroxetine extended-release tablets or placebo for a period of 3 months. In this trial,12.5 mg/day and 25 mg/day of paroxetine extended-release tablets, as luteal phase dosing, was statistically significantly more effective than placebo as measured by change from baseline to luteal phase VAS score at Month 3. There is insufficient information to determine the effect of race or age on outcome in Studies 8, 9, 10, and 11.

16 HOW SUPPLIED/STORAGE AND HANDLING Paroxetine extended-release tablets, USP are supplied as follows: 12.5 mg, yellow colored, round, biconvex, beveled edge film coated tablets, debossed with “L587” on one side and plain on other side. Bottle of 30 tablets with child-resistant closure, NDC 46708-766-30 Bottle of 1000 tablets, NDC 46708-766-91 25 mg, pink colored, round, biconvex, beveled edge film coated tablets, debossed with “L588” on one side and plain on other side. Bottle of 30 tablets with child-resistant closure, NDC 46708-767-30 Bottle of 1000 tablets, NDC 46708-767-91 37.5 mg, blue colored, round, biconvex, beveled edge film coated tablets, debossed with “L589” on one side and plain on other side. Bottle of 30 tablets with child-resistant closure, NDC 46708-768-30 Bottle of 1000 tablets, NDC 46708-768-91 Store at 20º to 25ºC (68º to 77ºF); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Suicidal Thoughts and Behaviors Advise patients and caregivers to look for the emergence of suicidality, especially early during treatment and when the dosage is adjusted up or down, and instruct them to report such symptoms to the healthcare provider [see Boxed Warning and Warnings and Precautions (5.1)] . Important Administration Instructions Instruct patients to swallow paroxetine extended-release tablets whole and to not chew or crush the tablets [see Dosage and Administration (2.1)] . Serotonin Syndrome Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of paroxetine extended-release tablets with other serotonergic drugs including triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, St. John’s Wort, and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid). Instruct patients to contact their health care provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome [see Warnings and Precautions (5.2), Drug Interactions (7.1)] . Concomitant Medications Advise patients to inform their physician if they are taking, or plan to take, any prescription or over-the-counter drugs, since there is a potential for drug-drug interactions [see Warning and Precautions (5.3), Drug Interactions (7)] . Increased Risk of Bleeding Inform patients about the concomitant use of paroxetine extended-release tablets with aspirin, NSAIDs, other antiplatelet drugs, warfarin, or other anticoagulants because the combined use has been associated with an increased risk of bleeding. Advise patients to inform their health care providers if they are taking or planning to take any prescription or over-the counter medications that increase the risk of bleeding [see Warnings and Precautions (5.5)] . Activation of Mania/Hypomania Advise patients and their caregivers to observe for signs of activation of mania/hypomania and instruct them to report such symptoms to the healthcare provider [see Warnings and Precautions (5.6)] . Discontinuation Syndrome Advise patients not to abruptly discontinue paroxetine extended-release tablets and to discuss any tapering regimen with their healthcare provider. Inform patients that adverse reactions can occur when paroxetine extended-release tablets are discontinued [See Warnings and Precautions (5.7)] . Sexual Dysfunction Advise patients that use of paroxetine extended-release tablets may cause symptoms of sexual dysfunction in both male and female patients. Inform patients that they should discuss any changes in sexual function and potential management strategies with their healthcare provider [see Warnings and Precautions (5.13)] . Embryo-Fetal Toxicity Advise women to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with paroxetine extended-release tablets. Advise women of risks associated with first trimester use of paroxetine and that use later in pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, tube feeding, and/or persistent pulmonary hypertension of the newborn (PPHN) [see Warnings and Precautions (5.4), Use in Specific Populations (8.1)] .

ster use of paroxetine and that use later in pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, tube feeding, and/or persistent pulmonary hypertension of the newborn (PPHN) [see Warnings and Precautions (5.4), Use in Specific Populations (8.1)] . Advise women that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to paroxetine extended-release tablets during pregnancy [see Warnings and Precautions (5.4), Use in Specific Populations (8.1)] . Lactation Advise breastfeeding women using paroxetine extended-release tablets to monitor infants for agitation, irritability, poor feeding and poor weight gain and to seek medical care if they notice these signs [see Use in Specific Populations (8.2)]. Females and Males of Reproductive Potential Advise men that paroxetine extended-release tablets may affect sperm quality, which may impair fertility; it is unknown if this effect is reversible [see Use in Specific Populations (8.3)] Allergic Reactions Advise patients to notify their healthcare provider if they develop an allergic reaction such as rash, hives, swelling, or difficulty breathing [see Adverse Reactions (6.1, 6.2)]. Manufactured by: Alembic Pharmaceuticals Limited (Formulation Division), Village Panelav, P. O. Tajpura, Near Baska, Taluka-Halol, Panchmahal 389350, Gujarat, India.

Medication Guide Paroxetine (pa rox’ e teen) Extended-Release Tablets What is the most important information I should know about paroxetine extended-release tablets? Paroxetine extended-release tablets can cause serious side effects, including: • Increased risk of suicidal thoughts or actions. Antidepressant medicines may increase suicidal thoughts and actions in some children and young adults within the first few months of treatment or when the dose is changed. Paroxetine extended-release tablets are not for use in people younger than 18 years of age. How can I watch for and try to prevent suicidal thoughts and actions? o Depression or other serious mental illnesses are the most important causes of suicidal thoughts and actions. o Pay close attention to any changes, especially sudden changes in mood, behavior, thoughts or feelings or if you develop suicidal thoughts or actions. This is very important when an antidepressant medicine is started or when the dose is changed. o Call your healthcare provider right away to report new or sudden changes in mood, behavior, thoughts or feelings or if you develop suicidal thoughts or actions. o Keep all follow-up visits with your healthcare provider as scheduled. Call your healthcare provider between visits as needed, especially if you have concerns about symptoms. Call your healthcare provider or get emergency medical help right away if you have any of the following symptoms, especially if they are new, worse, or worry you: o attempts to commit suicide o acting on dangerous impulses o acting aggressive or violent o thoughts about suicide or dying o new or worse depression o new or worse anxiety or panic attacks o feeling agitated, restless, angry, or irritable o trouble sleeping o an increase in activity and talking more than what is normal for you o other unusual changes in behavior or mood What are paroxetine extended-release tablets? Paroxetine extended-release tablets are a prescription medicine used in adults to treat: • A certain type of depression called Major Depressive Disorder (MDD) • Panic Disorder • Social Anxiety Disorder (SAD) • Premenstrual Dysphoric Disorder (PMDD) Do not take paroxetine extended-release tablets if you: • take a monoamine oxidase inhibitor (MAOI) • have stopped taking an MAOI in the last 14 days • are being treated with the antibiotic linezolid or intravenous methylene blue • are taking thioridazine • are taking pimozide • are allergic to paroxetine or any of the ingredients in paroxetine extended-release tablets. See the end of this Medication Guide for a complete list of ingredients in paroxetine extended-release tablets. Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI or one of these medicines, including intravenous methylene blue. Do not start taking an MAOI for at least 14 days after you stop treatment with paroxetine extended-release tablets. Before taking paroxetine extended-release tablets, tell your healthcare provider about all your medical conditions, including if you: • have heart problems • have or had bleeding problems • have, or have a family history of bipolar disorder, mania or hypomania • have or had seizures or convulsions • have glaucoma (high pressure in the eye) • have low sodium levels in your blood • have bone problems • have kidney or liver problems • are pregnant or plan to become pregnant. Paroxetine extended-release tablets may harm your unborn baby.

y of bipolar disorder, mania or hypomania • have or had seizures or convulsions • have glaucoma (high pressure in the eye) • have low sodium levels in your blood • have bone problems • have kidney or liver problems • are pregnant or plan to become pregnant. Paroxetine extended-release tablets may harm your unborn baby. • Taking paroxetine extended-release tablets during your first trimester of pregnancy may cause your baby to be at an increased risk of having a heart problem (cardiac malformations) at birth. • Taking paroxetine extended-release tablets during your third trimester of pregnancy may cause your baby to have breathing, temperature, and feeding problems, low muscle tone (floppy baby syndrome), and irritability after birth and may cause your baby to be at an increased risk of a serious lung problem at birth. Talk to your healthcare provider about the risk to your unborn baby if you take paroxetine extended-release tablets during pregnancy. • Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with paroxetine extended-release tablets. • There is a pregnancy registry for females who are exposed to paroxetine extended-release tablets during pregnancy. The purpose of the registry is to collect information about the health of females exposed to paroxetine extended-release tablets and their baby. If you become pregnant during treatment with paroxetine extended-release tablets talk to your healthcare provider about registering with the National Pregnancy Registry for Antidepressants at 1-866-961-2388 or visit online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/.” • are breastfeeding or plan to breastfeed. Paroxetine passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with paroxetine extended-release tablets. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Paroxetine extended-release tablets and some other medicines may affect each other causing possible serious side effects. Paroxetine extended-release tablets may affect the way other medicines work and other medicines may affect the way paroxetine extended-release tablets works. Especially tell your healthcare provider if you take: • medicines used to treat migraine headaches called triptans • tricyclic antidepressants • lithium • tramadol, fentanyl, meperidine, methadone, or other opioids • tryptophan • buspirone • amphetamines • St. John’s Wort • medicines that can affect blood clotting such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), or warfarin • diuretics • tamoxifen Ask your healthcare provider if you are not sure if you are taking any of these medicines. Your healthcare provider can tell you if it is safe to take paroxetine extended-release tablets with your other medicines. Do not start or stop any other medicines during treatment with paroxetine extended-release tablets without talking to your healthcare provider first. Stopping paroxetine extended-release tablets suddenly may cause you to have serious side effects. See, “What are the possible side effects of paroxetine extended-release tablets?” Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine. How should I take paroxetine extended-release tablets? • Take paroxetine extended-release tablets exactly as your healthcare provider tell you to. Your healthcare provider may need to change the dose of paroxetine extended-release tablets until it is the right dose for you. • Take paroxetine extended-release tablets 1 time each day in the morning.

extended-release tablets? • Take paroxetine extended-release tablets exactly as your healthcare provider tell you to. Your healthcare provider may need to change the dose of paroxetine extended-release tablets until it is the right dose for you. • Take paroxetine extended-release tablets 1 time each day in the morning. • Take paroxetine extended-release tablets with or without food. • Swallow paroxetine extended-release tablets whole. Do not chew or crush paroxetine extended-release tablets. • If you take too much paroxetine extended-release tablets, call your poison control center at 1-800-222-1222 or got to the nearest hospital emergency room right away. What are possible side effects of paroxetine extended-release tablets? Paroxetine extended-release tablets can cause serious side effects, including: • See, “What is the most important information I should know about paroxetine extended-release tablets?” • Serotonin syndrome. A potentially life-threatening problem called serotonin syndrome can happen when you take paroxetine extended-release tablets with certain other medicines. See, “Who should not take paroxetine extended-release tablets?” Call your healthcare provider or go to the nearest hospital emergency room right away if you have any of the following signs and symptoms of serotonin syndrome: o agitation o sweating o seeing or hearing things that o flushing are not real (hallucinations) o confusion o high body temperature (hyperthermia) o coma o shaking (tremors), stiff muscles, or muscle twitching o fast heart beat o loss of coordination o changes in blood pressure o seizures o dizziness o nausea, vomiting, diarrhea • Medicine interactions. Taking paroxetine extended-release tablets with certain other medicines including thioridazine and pimozide may increase the risk of developing a serious heart problem called QT prolongation. • Abnormal bleeding. Taking paroxetine extended-release tablets with aspirin, NSAIDs, or blood thinners may add to this risk. Tell your healthcare provider about any unusual bleeding or bruising. • Manic episodes. Manic episodes may happen in people with bipolar disorder who take paroxetine extended-release tablets. Symptoms may include: o greatly increased energy o severe problems sleeping o racing thoughts o reckless behavior o unusually grand ideas o excessive happiness or irritability o talking more or faster than usual • Discontinuation syndrome. Suddenly stopping paroxetine extended-release tablets may cause you to have serious side effects. Your healthcare provider may want to decrease your dose slowly. Symptoms may include: o nausea o electric shock feeling (paresthesia) o tiredness o sweating o tremor o problems sleeping o changes in your mood o anxiety o ringing in your ears (tinnitus) o irritability and agitation o confusion o seizures o dizziness o headache • Seizures (convulsions). Eye problems (angle-closure glaucoma). Paroxetine extended-release tablets may cause a type of eye problem called angle-closure glaucoma in people with certain other eye conditions. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are. • Low sodium levels in your blood (hyponatremia). Low sodium levels in your blood that may be serious and may cause death, can happen during treatment with paroxetine extended-release tablets. Elderly people and people who take certain medicines may be at a greater risk for developing low sodium levels in your blood.

. • Low sodium levels in your blood (hyponatremia). Low sodium levels in your blood that may be serious and may cause death, can happen during treatment with paroxetine extended-release tablets. Elderly people and people who take certain medicines may be at a greater risk for developing low sodium levels in your blood. Signs and symptoms may include: o headache o difficulty concentrating o memory changes o confusion o weakness and unsteadiness on your feet which can lead to falls In more severe or more sudden cases, signs and symptoms include: o seeing or hearing things that are not real (hallucinations) o fainting o seizures o coma o stopping breathing (respiratory arrest) • Bone fractures. • Sexual problems (dysfunction). Taking selective serotonin reuptake inhibitors (SSRIs), including paroxetine extended-release tablets, may cause sexual problems. Symptoms in males may include: o Delayed ejaculation or inability to have an ejaculation o Decreased sex drive o Problems getting or keeping an erection Symptoms in females may include: o Decreased sex drive o Delayed orgasm or inability to have an orgasm Talk to your healthcare provider if you develop any changes in your sexual function or if you have any questions or concerns about sexual problems during treatment with paroxetine extended-release tablets. There may be treatments your healthcare provider can suggest. The most common side effects paroxetine extended-release tablets include: • male and female sexual function problems • dry mouth • blurred vision • problems sleeping • weakness (asthenia) • nausea • constipation • sleepiness • decreased appetite • sweating • diarrhea • tremor • dizziness These are not all the possible side effects of paroxetine extended-release tablets. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store paroxetine extended-release tablets? • Store paroxetine extended-release tablets at room temperature between 68°F to 77°F (20°C to 25°C). • 30’s bottle comes in a child-resistant package. Keep paroxetine extended-release tablets and all medicines out of the reach of children. General information about the safe and effective use of paroxetine extended-release tablets. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not take paroxetine extended-release tablets for a condition for which it was not prescribed. Do not give paroxetine extended-release tablets to other people, even if they have the same symptoms that you have. It may harm them. You may ask your healthcare provider or pharmacist for information about paroxetine extended-release tablets that is written for healthcare professionals. What are the ingredients in paroxetine extended-release tablets? Active ingredient: paroxetine hydrochloride Inactive ingredients: colloidal silicon dioxide, glyceryl dibehenate, hypromellose, lactose monohydrate, magnesium stearate, methacrylic acid copolymer, povidone K-30, talc and triethyl citrate. The film-coating material contains hypromellose, polyethylene glycol 400, polyethylene glycol 6000 and titanium dioxide. Additionally, 12.5 mg tablets contain D&C Yellow No. 10 Lake, FD&C Yellow No. 6 Aluminium Lake and polysorbate 80, 25 mg tablets contain D&C Red No. 30 Lake and polysorbate 80 and 37.5 mg tablets contain FD&C Blue No. 2 Aluminium Lake and talc. Manufactured by: Alembic Pharmaceuticals Limited (Formulation Division), Village Panelav, P. O. Tajpura, Near Baska, Taluka-Halol, Panchmahal 389350, Gujarat, India. This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 09/2025

<table cellspacing="0" cellpadding="0" border="0"><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule" align="center" valign="middle"> <content styleCode="bold">Medication Guide Paroxetine (pa rox&#x2019; e teen) Extended-Release Tablets</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">What is the most important information I should know about paroxetine extended-release tablets? </content> <content styleCode="bold">Paroxetine extended-release tablets can cause serious side effects, including: &#x2022; Increased risk of suicidal thoughts or actions.</content> Antidepressant medicines may increase suicidal thoughts and actions in some children and young adults within the first few months of treatment or when the dose is changed. Paroxetine extended-release tablets are not for use in people younger than 18 years of age. <content styleCode="bold">How can I watch for and try to prevent suicidal thoughts and actions?</content> o Depression or other serious mental illnesses are the most important causes of suicidal thoughts and actions. o Pay close attention to any changes, especially sudden changes in mood, behavior, thoughts or feelings or if you develop suicidal thoughts or actions. This is very important when an antidepressant medicine is started or when the dose is changed. o Call your healthcare provider right away to report new or sudden changes in mood, behavior, thoughts or feelings or if you develop suicidal thoughts or actions. o Keep all follow-up visits with your healthcare provider as scheduled. Call your healthcare provider between visits as needed, especially if you have concerns about symptoms. <content styleCode="bold">Call your healthcare provider or get emergency medical help right away if you have any of the following symptoms, especially if they are new, worse, or worry you:</content> o attempts to commit suicide o acting on dangerous impulses o acting aggressive or violent o thoughts about suicide or dying o new or worse depression o new or worse anxiety or panic attacks o feeling agitated, restless, angry, or irritable o trouble sleeping o an increase in activity and talking more than what is normal for you o other unusual changes in behavior or mood </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">What are paroxetine extended-release tablets?</content> Paroxetine extended-release tablets are a prescription medicine used in adults to treat: &#x2022; A certain type of depression called Major Depressive Disorder (MDD) &#x2022; Panic Disorder &#x2022; Social Anxiety Disorder (SAD) &#x2022; Premenstrual Dysphoric Disorder (PMDD)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Do not take paroxetine extended-release tablets if you:</content> &#x2022; take a monoamine oxidase inhibitor (MAOI) &#x2022; have stopped taking an MAOI in the last 14 days &#x2022; are being treated with the antibiotic linezolid or intravenous methylene blue &#x2022; are taking thioridazine &#x2022; are taking pimozide &#x2022; are allergic to paroxetine or any of the ingredients in paroxetine extended-release tablets. See the end of this Medication Guide for a complete list of ingredients in paroxetine extended-release tablets.

otic linezolid or intravenous methylene blue &#x2022; are taking thioridazine &#x2022; are taking pimozide &#x2022; are allergic to paroxetine or any of the ingredients in paroxetine extended-release tablets. See the end of this Medication Guide for a complete list of ingredients in paroxetine extended-release tablets. Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI or one of these medicines, including intravenous methylene blue. <content styleCode="bold">Do not start taking an MAOI for at least 14 days after you stop treatment with paroxetine extended-release tablets.</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Before taking paroxetine extended-release tablets, tell your healthcare provider about all your medical conditions, including if you:</content> &#x2022; have heart problems &#x2022; have or had bleeding problems &#x2022; have, or have a family history of bipolar disorder, mania or hypomania &#x2022; have or had seizures or convulsions &#x2022; have glaucoma (high pressure in the eye) &#x2022; have low sodium levels in your blood &#x2022; have bone problems &#x2022; have kidney or liver problems &#x2022; are pregnant or plan to become pregnant. Paroxetine extended-release tablets may harm your unborn baby. &#x2022; Taking paroxetine extended-release tablets during your first trimester of pregnancy may cause your baby to be at an increased risk of having a heart problem (cardiac malformations) at birth. &#x2022; Taking paroxetine extended-release tablets during your third trimester of pregnancy may cause your baby to have breathing, temperature, and feeding problems, low muscle tone (floppy baby syndrome), and irritability after birth and may cause your baby to be at an increased risk of a serious lung problem at birth. Talk to your healthcare provider about the risk to your unborn baby if you take paroxetine extended-release tablets during pregnancy. &#x2022; Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with paroxetine extended-release tablets. &#x2022; There is a pregnancy registry for females who are exposed to paroxetine extended-release tablets during pregnancy. The purpose of the registry is to collect information about the health of females exposed to paroxetine extended-release tablets and their baby. If you become pregnant during treatment with paroxetine extended-release tablets talk to your healthcare provider about registering with the National Pregnancy Registry for Antidepressants at 1-866-961-2388 or visit online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/.&#x201D; &#x2022; are breastfeeding or plan to breastfeed. Paroxetine passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with paroxetine extended-release tablets. <content styleCode="bold">Tell your healthcare provider about all the medicines you take,</content> including prescription and over-the-counter medicines, vitamins, and herbal supplements. Paroxetine extended-release tablets and some other medicines may affect each other causing possible serious side effects. Paroxetine extended-release tablets may affect the way other medicines work and other medicines may affect the way paroxetine extended-release tablets works. <content styleCode="bold">Especially tell your healthcare provider if you take:</content> &#x2022; medicines used to treat migraine headaches called triptans &#x2022; tricyclic antidepressants &#x2022; lithium &#x2022; tramadol, fentanyl, meperidine, methadone, or other opioids &#x2022; tryptophan &#x2022; buspirone &#x2022; amphetamines &#x2022; St.

ally tell your healthcare provider if you take:</content> &#x2022; medicines used to treat migraine headaches called triptans &#x2022; tricyclic antidepressants &#x2022; lithium &#x2022; tramadol, fentanyl, meperidine, methadone, or other opioids &#x2022; tryptophan &#x2022; buspirone &#x2022; amphetamines &#x2022; St. John&#x2019;s Wort &#x2022; medicines that can affect blood clotting such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), or warfarin &#x2022; diuretics &#x2022; tamoxifen Ask your healthcare provider if you are not sure if you are taking any of these medicines. Your healthcare provider can tell you if it is safe to take paroxetine extended-release tablets with your other medicines. Do not start or stop any other medicines during treatment with paroxetine extended-release tablets without talking to your healthcare provider first. Stopping paroxetine extended-release tablets suddenly may cause you to have serious side effects. See, <content styleCode="bold">&#x201C;What are the possible side effects of paroxetine extended-release tablets?&#x201D;</content> Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine. </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">How should I take paroxetine extended-release tablets?</content> &#x2022; Take paroxetine extended-release tablets exactly as your healthcare provider tell you to. Your healthcare provider may need to change the dose of paroxetine extended-release tablets until it is the right dose for you. &#x2022; Take paroxetine extended-release tablets 1 time each day in the morning. &#x2022; Take paroxetine extended-release tablets with or without food. &#x2022; Swallow paroxetine extended-release tablets whole. <content styleCode="bold">Do not </content>chew or crush paroxetine extended-release tablets. &#x2022; If you take too much paroxetine extended-release tablets, call your poison control center at 1-800-222-1222 or got to the nearest hospital emergency room right away.</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">What are possible side effects of paroxetine extended-release tablets?</content> <content styleCode="bold">Paroxetine extended-release tablets can cause serious side effects, including:</content> &#x2022; See, <content styleCode="bold">&#x201C;What is the most important information I should know about paroxetine extended-release tablets?&#x201D;</content> &#x2022; <content styleCode="bold">Serotonin syndrome.</content> A potentially life-threatening problem called serotonin syndrome can happen when you take paroxetine extended-release tablets with certain other medicines. See, &#x201C;Who should not take paroxetine extended-release tablets?&#x201D; <content styleCode="bold">Call your healthcare provider or go to the nearest hospital emergency room right away</content> if you have any of the following signs and symptoms of serotonin syndrome: o agitation o sweating o seeing or hearing things that o flushing are not real (hallucinations) o confusion o high body temperature (hyperthermia) o coma o shaking (tremors), stiff muscles, or muscle twitching o fast heart beat o loss of coordination o changes in blood pressure o seizures o dizziness o nausea, vomiting, diarrhea &#x2022; <content styleCode="bold">Medicine interactions.</content> Taking paroxetine extended-release tablets with certain other medicines including thioridazine and pimozide may increase the risk of developing a serious heart problem called QT prolongation.

pressure o seizures o dizziness o nausea, vomiting, diarrhea &#x2022; <content styleCode="bold">Medicine interactions.</content> Taking paroxetine extended-release tablets with certain other medicines including thioridazine and pimozide may increase the risk of developing a serious heart problem called QT prolongation. &#x2022; <content styleCode="bold">Abnormal bleeding.</content> Taking paroxetine extended-release tablets with aspirin, NSAIDs, or blood thinners may add to this risk. Tell your healthcare provider about any unusual bleeding or bruising. &#x2022; <content styleCode="bold">Manic episodes. </content>Manic episodes may happen in people with bipolar disorder who take paroxetine extended-release tablets. Symptoms may include: o greatly increased energy o severe problems sleeping o racing thoughts o reckless behavior o unusually grand ideas o excessive happiness or irritability o talking more or faster than usual &#x2022; <content styleCode="bold">Discontinuation syndrome.</content> Suddenly stopping paroxetine extended-release tablets may cause you to have serious side effects. Your healthcare provider may want to decrease your dose slowly. Symptoms may include: o nausea o electric shock feeling (paresthesia) o tiredness o sweating o tremor o problems sleeping o changes in your mood o anxiety o ringing in your ears (tinnitus) o irritability and agitation o confusion o seizures o dizziness o headache &#x2022; <content styleCode="bold">Seizures (convulsions).</content> <content styleCode="bold"> Eye problems (angle-closure glaucoma).</content> Paroxetine extended-release tablets may cause a type of eye problem called angle-closure glaucoma in people with certain other eye conditions. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are. &#x2022; <content styleCode="bold">Low sodium levels in your blood (hyponatremia).</content> Low sodium levels in your blood that may be serious and may cause death, can happen during treatment with paroxetine extended-release tablets. Elderly people and people who take certain medicines may be at a greater risk for developing low sodium levels in your blood. Signs and symptoms may include: o headache o difficulty concentrating o memory changes o confusion o weakness and unsteadiness on your feet which can lead to falls <content styleCode="bold">In more severe or more sudden cases, signs and symptoms include:</content> o seeing or hearing things that are not real (hallucinations) o fainting o seizures o coma o stopping breathing (respiratory arrest) &#x2022; <content styleCode="bold">Bone fractures.</content> &#x2022; <content styleCode="bold">Sexual problems (dysfunction).</content> Taking selective serotonin reuptake inhibitors (SSRIs), including paroxetine extended-release tablets, may cause sexual problems. Symptoms in males may include: o Delayed ejaculation or inability to have an ejaculation o Decreased sex drive o Problems getting or keeping an erection Symptoms in females may include: o Decreased sex drive o Delayed orgasm or inability to have an orgasm Talk to your healthcare provider if you develop any changes in your sexual function or if you have any questions or concerns about sexual problems during treatment with paroxetine extended-release tablets. There may be treatments your healthcare provider can suggest.

rive o Delayed orgasm or inability to have an orgasm Talk to your healthcare provider if you develop any changes in your sexual function or if you have any questions or concerns about sexual problems during treatment with paroxetine extended-release tablets. There may be treatments your healthcare provider can suggest. <content styleCode="bold">The most common side effects paroxetine extended-release tablets include:</content> &#x2022; male and female sexual function problems &#x2022; dry mouth &#x2022; blurred vision &#x2022; problems sleeping &#x2022; weakness (asthenia) &#x2022; nausea &#x2022; constipation &#x2022; sleepiness &#x2022; decreased appetite &#x2022; sweating &#x2022; diarrhea &#x2022; tremor &#x2022; dizziness These are not all the possible side effects of paroxetine extended-release tablets. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold"> How should I store paroxetine extended-release tablets?</content> &#x2022; Store paroxetine extended-release tablets at room temperature between 68&#xB0;F to 77&#xB0;F (20&#xB0;C to 25&#xB0;C). &#x2022; 30&#x2019;s bottle comes in a child-resistant package. <content styleCode="bold">Keep paroxetine extended-release tablets and all medicines out of the reach of children.</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">General information about the safe and effective use of paroxetine extended-release tablets.</content> Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not take paroxetine extended-release tablets for a condition for which it was not prescribed. Do not give paroxetine extended-release tablets to other people, even if they have the same symptoms that you have. It may harm them. You may ask your healthcare provider or pharmacist for information about paroxetine extended-release tablets that is written for healthcare professionals.</td></tr><tr><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">What are the ingredients in paroxetine extended-release tablets? </content> <content styleCode="bold">Active ingredient: </content>paroxetine hydrochloride <content styleCode="bold">Inactive ingredients:</content> colloidal silicon dioxide, glyceryl dibehenate, hypromellose, lactose monohydrate, magnesium stearate, methacrylic acid copolymer, povidone K-30, talc and triethyl citrate. The film-coating material contains hypromellose, polyethylene glycol 400, polyethylene glycol 6000 and titanium dioxide. Additionally, 12.5 mg tablets contain D&amp;C Yellow No. 10 Lake, FD&amp;C Yellow No. 6 Aluminium Lake and polysorbate 80, 25 mg tablets contain D&amp;C Red No. 30 Lake and polysorbate 80 and 37.5 mg tablets contain FD&amp;C Blue No. 2 Aluminium Lake and talc. Manufactured by: Alembic Pharmaceuticals Limited (Formulation Division), Village Panelav, P. O. Tajpura, Near Baska, Taluka-Halol, Panchmahal 389350, Gujarat, India. </td></tr></tbody></table>