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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 )] . Vilazodone hydrochloride 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. Antidepressants increase the risk of suicidal thoughts and behaviors in pediatric and young adult patients. ( 5.1 ) Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors. ( 5.1 ) Vilazodone hydrochloride tablets are not approved for use in pediatric patients. ( 8.4 )

1 INDICATIONS AND USAGE Vilazodone hydrochloride tablets are indicated for the treatment of major depressive disorder (MDD) in adults [see Clinical Studies ( 14 )] . Vilazodone hydrochloride tablets are indicated for the treatment of major depressive disorder (MDD) in adults. ( 1 )

2 DOSAGE AND ADMINISTRATION Recommended target dosage: 20 mg to 40 mg once daily with food. ( 2.1 , 12.3 ) To titrate: start with initial dosage of 10 mg once daily for 7 days, followed by 20 mg once daily. The dose may be increased up to 40 mg once daily after a minimum of 7 days between dosage increases. ( 2.1 ) Prior to initiating vilazodone hydrochloride tablets, screen for bipolar disorder. ( 2.2 , 5.4 ) When discontinuing vilazodone hydrochloride tablets, reduce dosage gradually. ( 2.4 , 5.5 ) 2.1 Dosage for Treatment of Major Depressive Disorder The recommended target dosage for vilazodone hydrochloride tablets is 20 mg to 40 mg orally once daily with food [see Clinical Pharmacology ( 12.3 ), Clinical Studies ( 14 )] . To achieve the target dosage, titrate vilazodone hydrochloride tablets as follows: Start with an initial dosage of 10 mg once daily with food for 7 days, Then increase to 20 mg once daily with food. The dose may be increased up to 40 mg once daily with food after a minimum of 7 days between dosage increases. If a dose is missed, it should be taken as soon as the patient remembers. If it is almost time for the next dose, the patient should skip the missed dose and take the next dose at the regular time. Two doses should not be taken at the same time. 2.2 Screen for Bipolar Disorder Prior to Starting Vilazodone Hydrochloride Tablets Prior to initiating treatment with vilazodone hydrochloride tablets or another antidepressant, screen patients for a personal or family history of bipolar disorder, mania, or hypomania [see Warnings and Precautions ( 5.4 )] . 2.3 Switching to or from a Monoamine Oxidase Inhibitor Antidepressant At least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI) antidepressant and initiation of vilazodone hydrochloride tablets. In addition, at least 14 days must elapse after stopping vilazodone hydrochloride tablets before starting an MAOI antidepressant [see Contraindications ( 4 ), Warnings and Precautions ( 5.2 )] . 2.4 Dosage Adjustments with CYP3A4 Inhibitors or Inducers Patients receiving concomitant CYP3A4 inhibitors : During concomitant use of a strong CYP3A4 inhibitor (e.g., itraconazole, clarithromycin, voriconazole), the vilazodone hydrochloride tablets dose should not exceed 20 mg once daily. The original vilazodone hydrochloride tablet dose level, can be resumed when the CYP3A4 inhibitor is discontinued [see Drug Interactions ( 7 )] . Patients receiving concomitant CYP3A4 inducers : Based on clinical response, consider increasing the dosage of vilazodone hydrochloride tablets by 2-fold, up to a maximum 80 mg once daily, over 1 to 2 weeks in patients taking strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin) for greater than 14 days. If CYP3A4 inducers are discontinued, gradually reduce the vilazodone hydrochloride tablets dosage to its original level over 1 to 2 weeks [see Drug Interactions ( 7 )] . 2.5 Discontinuing Treatment with Vilazodone Hydrochloride Tablets Adverse reactions may occur upon discontinuation of vilazodone hydrochloride tablets [see Warnings and Precautions ( 5.5 )] . A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible. Vilazodone hydrochloride tablets should be down tapered from the 40 mg once daily dose to 20 mg once daily for 4 days, followed by 10 mg once daily for 3 days.

done hydrochloride tablets [see Warnings and Precautions ( 5.5 )] . A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible. Vilazodone hydrochloride tablets should be down tapered from the 40 mg once daily dose to 20 mg once daily for 4 days, followed by 10 mg once daily for 3 days. Patients taking vilazodone hydrochloride tablets 20 mg once daily should be tapered to 10 mg once daily for 7 days.

3 DOSAGE FORMS AND STRENGTHS Vilazodone hydrochloride tablets are available as 10 mg, 20 mg, and 40 mg film-coated tablets. 10 mg pink, oval shaped tablet, debossed with “TV” on one side and “V7” on the other side 20 mg beige, oval shaped tablet, debossed with “TV” on one side and “V71” on the other side 40 mg blue, oval shaped tablet debossed with “TV” on one side and “V72” on the other side Tablets: 10 mg, 20 mg, and 40 mg ( 3 )

4 CONTRAINDICATIONS Vilazodone hydrochloride tablets are contraindicated in: Patients taking, or within 14 days of stopping, monoamine oxidase inhibitors (MAOIs), including MAOIs such as linezolid or intravenous methylene blue, because of an increased risk of serotonin syndrome [see Warnings and Precautions ( 5.2 ), Drug Interactions ( 7 )] . Concomitant use of monoamine oxidase inhibitors (MAOIs), or use within 14 days of stopping MAOIs. ( 4 )

5 WARNINGS AND PRECAUTIONS Serotonin Syndrome: Increased risk when coadministered with other serotonergic agents, but also when taken alone. If it occurs, discontinue vilazodone hydrochloride tablets and serotonergic agents and initiate supportive treatment. ( 5.2 ) Increased Risk of Bleeding: Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), other antiplatelet drugs, warfarin, and other anticoagulants may increase this risk. ( 5.3 ) Activation of Mania/Hypomania: Screen patients for bipolar disorder. ( 5.4 ) Seizures: Can occur with treatment. Use with caution in patients with a seizure disorder. ( 5.6 ) Angle Closure Glaucoma: Avoid use of antidepressants, including vilazodone hydrochloride, in patients with untreated anatomically narrow angles. ( 5.7 ) Sexual Dysfunction: Vilazodone hydrochloride tablets may cause symptoms of sexual dysfunction. ( 5.9 ) 5.1 Suicidal Thoughts and Behavior 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 over 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater in antidepressant-treated patients 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 1. Table 1: Risk Differences of the Number of Patients with Suicidal Thoughts or Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients Age Range (years) Drug-Placebo Difference in Number of Patients with Suicidal Thoughts or Behaviors per 1000 Patients Treated Increases Compared to Placebo <18 14 additional patients 18 to 24 5 additional patients Decreases Compared to Placebo 25 to 64 1 fewer patient ≥65 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 studies 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 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 vilazodone hydrochloride, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors. 5.2 Serotonin Syndrome Serotonin and norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitor (SSRIs), including vilazodone hydrochloride, can precipitate serotonin syndrome, a potentially life-threatening condition.

ly worse, or who are experiencing emergent suicidal thoughts or behaviors. 5.2 Serotonin Syndrome Serotonin and norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitor (SSRIs), including vilazodone hydrochloride, 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, meperidine, methadone, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [see Contraindications ( 4 ) and Drug Interactions ( 7 )] . Serotonin syndrome can also occur when these drugs are used alone. Symptoms of serotonin syndrome were noted in 0.1% of MDD patients treated with vilazodone hydrochloride in premarketing clinical trials. 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 vilazodone hydrochloride with MAOIs is contraindicated. In addition, do not initiate vilazodone hydrochloride 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 vilazodone hydrochloride, discontinue vilazodone hydrochloride before initiating treatment with the MAOI [see Contraindications ( 4 ), Drug Interactions ( 7.1 )] . Monitor all patients taking vilazodone hydrochloride for the emergence of serotonin syndrome. Discontinue treatment with vilazodone hydrochloride tablets and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of vilazodone hydrochloride with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms. 5.3 Increased Risk of Bleeding Drugs that interfere with serotonin reuptake inhibition, including vilazodone hydrochloride, 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. 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 ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages. Inform patients about the increased risk of bleeding associated with the concomitant use of vilazodone hydrochloride and antiplatelet agents or anticoagulants. For patients taking warfarin, carefully monitor coagulation indices when initiating, titrating, or discontinuing vilazodone hydrochloride.

eatening hemorrhages. Inform patients about the increased risk of bleeding associated with the concomitant use of vilazodone hydrochloride and antiplatelet agents or anticoagulants. For patients taking warfarin, carefully monitor coagulation indices when initiating, titrating, or discontinuing vilazodone hydrochloride. 5.4 Activation of Mania or Hypomania In patients with bipolar disorder, treating a depressive episode with vilazodone hydrochloride or another antidepressant may precipitate a mixed/manic episode. In controlled clinical trials, patients with bipolar disorder were excluded; however, symptoms of mania or hypomania were reported in 0.1% of undiagnosed patients treated with vilazodone hydrochloride. Prior to initiating treatment with vilazodone hydrochloride, screen patients for any personal or family history of bipolar disorder, mania, or hypomania [see Dosage and Administration ( 2.2 )] . 5.5 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 ( 2.5 )] . 5.6 Seizures Vilazodone hydrochloride has not been systematically evaluated in patients with a seizure disorder. Patients with a history of seizures were excluded from clinical studies. Vilazodone hydrochloride should be prescribed with caution in patients with a seizure disorder. 5.7 Angle-Closure Glaucoma The pupillary dilation that occurs following use of many antidepressant drugs including vilazodone hydrochloride may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy. Avoid use of antidepressants, including vilazodone hydrochloride, in patients with untreated anatomically narrow angles. 5.8 Hyponatremia Hyponatremia may occur as a result of treatment with SNRIs and SSRIs, including vilazodone hydrochloride. Cases of 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 vilazodone hydrochloride 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 and SNRIs [see Use in Specific Populations ( 8.5 )] . 5.9 Sexual Dysfunction Use of SSRIs, including vilazodone hydrochloride tablets, 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 vilazodone hydrochloride tablets and to inquire specifically about changes in sexual function during treatment, because sexual function may not be spontaneously reported.

may result in decreased libido and delayed or absent orgasm. It is important for prescribers to inquire about sexual function prior to initiation of vilazodone hydrochloride tablets 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 width="1000px" cellspacing="0" cellpadding="0" border="1"><caption>Table 1: Risk Differences of the Number of Patients with Suicidal Thoughts or Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients</caption><col width="1pt"/><col width="459pt"/><tbody><tr><td align="center"><paragraph><content styleCode="bold">Age Range</content></paragraph><paragraph><content styleCode="bold">(years)</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Drug-Placebo Difference in Number of Patients with Suicidal Thoughts or Behaviors per 1000 Patients Treated</content></paragraph></td></tr><tr><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Increases Compared to Placebo</content></paragraph></td></tr><tr><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>&lt;18</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>14 additional patients</paragraph></td></tr><tr><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>18 to 24</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>5 additional patients</paragraph></td></tr><tr><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Decreases Compared to Placebo</content></paragraph></td></tr><tr><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>25 to 64</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>1 fewer patient</paragraph></td></tr><tr><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>&#x2265;65</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>6 fewer patients</paragraph></td></tr></tbody></table>

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Suicidal Thoughts and Behaviors in Adolescents and Young Adults [see Warnings and Precautions ( 5.1 )]. Serotonin Syndrome [see Warnings and Precautions ( 5.2 )]. Increased Risk of Bleeding [see Warnings and Precautions ( 5.3 )]. Activation of Mania or Hypomania [see Warnings and Precautions ( 5.4 )]. Discontinuation Syndrome [see Warnings and Precautions ( 5.5 )] . Seizures [see Warnings and Precautions ( 5.6 )]. Angle-Closure Glaucoma [see Warnings and Precautions ( 5.7 )]. Hyponatremia [see Warnings and Precautions ( 5.8 )]. Sexual Dysfunction [see Warnings and Precautions ( 5.9 )]. Most common adverse reactions (incidence ≥5% and at least twice the rate of placebo): diarrhea, nausea, vomiting, and insomnia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 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 and varying lengths of time, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect rates observed in practice. The most commonly observed adverse reactions in vilazodone hydrochloride-treated patients with major depressive disorder (MDD) in placebo-controlled studies (incidence ≥5% and at least twice the rate of placebo) were diarrhea, nausea, vomiting, and insomnia. Patient Exposure The safety of vilazodone hydrochloride was evaluated in 3,007 patients (18 to 70 years of age) diagnosed with MDD who participated in clinical studies, representing 676 patient-years of exposure. In an open-label 52 week study at 40 mg daily, 599 patients were exposed to vilazodone hydrochloride for a total of 348 patient-years. The adverse reaction information presented below was derived from studies of vilazodone hydrochloride 20 mg and 40 mg daily in patients with MDD including: Four placebo-controlled 8 to 10-week studies in 2,233 patients, including 1,266 vilazodone hydrochloride-treated patients; and An open-label 52-week study of 599 vilazodone hydrochloride-treated patients. These studies included a titration period of 10 mg daily for 7 days, followed by 20 mg daily for 7 days or to 40 mg daily over 2 weeks. In these clinical trials, vilazodone hydrochloride was administered with food. Adverse reactions reported as reasons for discontinuation of treatment In these studies, 7.3% of the vilazodone hydrochloride-treated patients discontinued treatment due to an adverse reaction, compared with 3.5% of placebo-treated patients. The most common adverse reaction leading to discontinuation in at least 1% of the vilazodone hydrochloride-treated patients in the placebo-controlled studies was nausea (1.4%). Common adverse reactions in placebo-controlled MDD studies Table 2 shows the incidence of common adverse reactions occurring in ≥2% of vilazodone hydrochloride-treated patients and greater than the rate of placebo-treated patients in MDD Studies. There were no dose-related adverse reactions between 20 mg and 40 mg reported.

n adverse reactions in placebo-controlled MDD studies Table 2 shows the incidence of common adverse reactions occurring in ≥2% of vilazodone hydrochloride-treated patients and greater than the rate of placebo-treated patients in MDD Studies. There were no dose-related adverse reactions between 20 mg and 40 mg reported. Table 2: Common Adverse Reactions Occurring in ≥2% of Vilazodone Hydrochloride-treated Patients and Greater than the Rate of Placebo-Treated Patients System Organ Class Preferred Term Placebo N=967 Vilazodone Hydrochloride 20 mg/day N=288 Vilazodone Hydrochloride 40 mg/day N=978 Gastrointestinal disorders Diarrhea 10% 26% 29% Nausea 7% 22% 24% Dry mouth 5% 8% 7% Vomiting 2% 4% 5% Abdominal pain 1 3% 7% 4% Dyspepsia 2% 2% 3% Flatulence 1% 3% 3% Gastroenteritis 1% 1% 2% Abdominal distension 1% 2% 1% Nervous system disorders Headache 2 14% 15% 14% Dizziness 5% 6% 8% Somnolence 2% 4% 5% Paresthesia 1% 1% 2% Psychiatric disorders Insomnia 2% 7% 6% Abnormal dreams 2% 2% 3% Restlessness 3 1% 2% 3% General disorders Fatigue 3% 4% 3% Cardiac disorders Palpitations <1% 1% 2% Metabolism and nutrition disorders Increased appetite 1% 1% 3% Musculoskeletal and connective tissue disorders Arthralgia 1% 2% 1% Investigations Increased weight 1% 1% 2% 1 Includes abdominal discomfort, abdominal pain upper, and abdominal pain. 2 Includes headache and tension headache 3 Includes restlessness, akathisia, and restless legs syndrome Sexual adverse reactions are presented in Table 3 Sexual adverse reactions Table 3 displays the most common sexual adverse reactions in the placebo-controlled MDD studies. Table 3: Common Sexual Adverse Reactions Occurring in ≥2% of Vilazodone Hydrochloride-treated Patients and Greater than the Rate of Placebo-Treated Patients Preferred Term Males Females Placebo Vilazodone Hydrochloride 20 mg/day Vilazodone Hydrochloride 40 mg/day Placebo Vilazodone Hydrochloride 20 mg/day Vilazodone Hydrochloride 40 mg/day N=416 N=122 N=417 N=551 N=166 N=561 Abnormal Orgasm * <1% 2% 2% 0% 1% 1% Erectile dysfunction 1% 0% 3% - - - Libido decreased <1% 3% 4% <1% 2% 2% Ejaculation disorder 0% 1% 2% - - - − Not applicable * Includes abnormal orgasm and anorgasmia Other adverse reactions observed in clinical studies The following list does not include reactions: 1) already listed in previous tables or elsewhere in labeling, 2) for which a drug cause was remote, 3) which were so general as to be uninformative, 4) which were not considered to have significant clinical implications, or 5) which occurred at a rate equal to or less than placebo. Reactions are categorized by body system according to the following definitions: frequent adverse reactions are those occurring in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1000 patients; rare reactions are those occurring in fewer than 1/1000 patients: Cardiac disorders: infrequent : ventricular extrasystoles Eye disorders: infrequent : dry eye, vision blurred, rare: cataracts Nervous System: frequent : sedation, tremor; infrequent: migraine Psychiatric disorders: infrequent : panic attack Skin and subcutaneous tissue disorders: infrequent: hyperhidrosis, night sweats 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of vilazodone hydrochloride. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure.

marketing Experience The following adverse reactions have been identified during post-approval use of vilazodone hydrochloride. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure. Reports of adverse reactions temporally associated with vilazodone hydrochloride that have been received since market introduction and that are not listed above include the following: General Disorders and Administration Site Conditions: irritability Nervous System Disorders: sleep paralysis Psychiatric Disorders: hallucinations, suicide attempt, suicidal ideation Skin and subcutaneous tissue disorders: rash, generalized rash, urticaria, drug eruption Gastrointestinal System: acute pancreatitis Respiratory, Thoracic and Mediastinal Disorders: anosmia, hyposmia

<table width="1000px" cellspacing="0" cellpadding="4"><caption>Table 2: Common Adverse Reactions Occurring in &#x2265;2% of Vilazodone Hydrochloride-treated Patients and Greater than the Rate of Placebo-Treated Patients</caption><col width="189.9pt"/><col width="67.5pt"/><col width="130.5pt"/><col width="1.75in"/><tbody><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">System Organ Class</content></paragraph><paragraph><content styleCode="bold">Preferred Term</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Placebo</content></paragraph><paragraph><content styleCode="bold">N=967</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Vilazodone Hydrochloride</content></paragraph><paragraph><content styleCode="bold">20 mg/day</content></paragraph><paragraph><content styleCode="bold">N=288</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Vilazodone Hydrochloride</content></paragraph><paragraph><content styleCode="bold">40 mg/day</content></paragraph><paragraph><content styleCode="bold">N=978</content></paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Gastrointestinal disorders</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Diarrhea</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>10%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>26%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>29%</paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Nausea</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>7%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>22%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>24%</paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Dry mouth</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>5%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>8%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>7%</paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Vomiting</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>2%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>4%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>5%</paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Abdominal pain ¹</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>3%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>7%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>4%</paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Dysp

styleCode=" Botrule Toprule Lrule Rrule"><paragraph>3%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>7%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>4%</paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Dysp epsia</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>2%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>2%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>3%</paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Flatulence</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>1%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>3%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>3%</paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Gastroenteritis</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>1%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>1%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>2%</paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Abdominal distension</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>1%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>2%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>1%</paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Nervous system disorders</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Headache ²</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>14%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>15%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>14%</paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Dizziness</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>5%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>6%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>8%</paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Somnolence</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>2%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>4%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>5%</paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Paresthesia</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>1%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>1%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>2%</paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Psychiatric disorders</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule Toprule Lrule Rrule"

</tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Psychiatric disorders</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule Toprule Lrule Rrule" /></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Insomnia</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>2%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>7%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>6%</paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Abnormal dreams</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>2%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>2%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>3%</paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Restlessness ³</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>1%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>2%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>3%</paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">General disorders</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Fatigue</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>3%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>4%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>3%</paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Cardiac disorders</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Palpitations</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>&lt;1%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>1%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>2%</paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Metabolism and nutrition disorders</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Increased appetite</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>1%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>1%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>3%</paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Musculoskeletal and connective tissue disorders</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule

tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Musculoskeletal and connective tissue disorders</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Arthralgia</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>1%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>2%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>1%</paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Investigations</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Increased weight</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>1%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>1%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>2%</paragraph></td></tr><tr><td colspan="4"><paragraph>¹Includes abdominal discomfort, abdominal pain upper, and abdominal pain. </paragraph></td></tr><tr><td colspan="4"><paragraph>²Includes headache and tension headache </paragraph></td></tr><tr><td colspan="4"><paragraph>³Includes restlessness, akathisia, and restless legs syndrome Sexual adverse reactions are presented in Table 3 </paragraph></td></tr></tbody></table>

Toprule Lrule Rrule"/></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Arthralgia</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>1%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>2%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>1%</paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Investigations</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Increased weight</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>1%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>1%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>2%</paragraph></td></tr><tr><td colspan="4"><paragraph>¹Includes abdominal discomfort, abdominal pain upper, and abdominal pain. </paragraph></td></tr><tr><td colspan="4"><paragraph>²Includes headache and tension headache </paragraph></td></tr><tr><td colspan="4"><paragraph>³Includes restlessness, akathisia, and restless legs syndrome Sexual adverse reactions are presented in Table 3 </paragraph></td></tr></tbody></table> <table width="1000px" cellspacing="0" cellpadding="4"><caption>Table 3: Common Sexual Adverse Reactions Occurring in &#x2265;2% of Vilazodone Hydrochloride-treated Patients and Greater than the Rate of Placebo-Treated Patients</caption><col width="72.9pt"/><col width="211.5pt"/><col width="3.7in"/><col/><col/><col/><col/><tbody><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Preferred Term</content></paragraph></td><td align="center" colspan="3" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Males</content></paragraph></td><td align="center" colspan="3" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Females</content></paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Placebo</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Vilazodone</content></paragraph><paragraph><content styleCode="bold">Hydrochloride</content></paragraph><paragraph><content styleCode="bold">20 mg/day</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Vilazodone Hydrochloride</content></paragraph><paragraph><content styleCode="bold">40 mg/day</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Placebo</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Vilazodone Hydrochloride</content></paragraph><paragraph><content styleCode="bold">20 mg/day</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Vilazodone</content></paragraph><paragraph><content styleCode="bold">Hydrochloride</content></paragraph><paragraph><content styleCode="bold">40 mg/day</content></paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"/><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">N=416</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">N=122</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">N=417</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">N=551</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">N=166</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">N=561</content></paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Abnormal Orgasm ^*</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>&lt;1%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>2%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>2%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>0%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>1%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragrap

styleCode=" Botrule Toprule Lrule Rrule"><paragraph>2%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>0%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>1%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragrap h>1%</paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Erectile dysfunction</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>1%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>0%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>3%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>-</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>-</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>-</paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Libido decreased</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>&lt;1%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>3%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>4%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>&lt;1%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>2%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>2%</paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Ejaculation disorder</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>0%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>1%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>2%</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>-</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>-</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>-</paragraph></td></tr><tr><td colspan="7"><paragraph>&#x2212; Not applicable</paragraph><paragraph>^*Includes abnormal orgasm and anorgasmia </paragraph></td></tr></tbody></table>

7 DRUG INTERACTIONS CYP3A4 Inhibitors: The vilazodone hydrochloride tablets dose should not exceed 20 mg once daily when coadministered with strong CYP3A4 inhibitors. ( 2.4 , 7 ) CYP3A4 Inducers: Consider increasing vilazodone hydrochloride tablets dosage by 2-fold, up to 80 mg once-daily over 1 to 2 weeks when used concomitantly with strong CYP3A4 inducers for greater than 14 days. ( 2.4 , 7 ) 7.1 Drugs Having Clinically Important Interactions with Vilazodone Hydrochloride Table 4: Clinically Important Drug Interactions with Vilazodone Hydrochloride Concomitant Drug Name or Drug Class Clinical Rationale Clinical Recommendation Monoamine Oxidase Inhibitors (MAOIs) The concomitant use of MAOIs and serotonergic drugs including vilazodone hydrochloride increases the risk of serotonin syndrome. Vilazodone hydrochloride is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [see Contraindications ( 4 ), Dosage and Administration ( 2.3 ), and Warnings and Precautions ( 5.2 )] . Other Serotonergic Drugs Concomitant use of vilazodone hydrochloride with other serotonergic drugs (including other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, buspirone, amphetamines, tryptophan, and St. John’s Wort) increases the risk of serotonin syndrome. Monitor patients for signs and symptoms of serotonin syndrome, particularly during vilazodone hydrochloride initiation. If serotonin syndrome occurs, consider discontinuation of vilazodone hydrochloride and/or concomitant serotonergic drugs [see Warnings and Precautions ( 5.2 )] . Antiplatelet Agents and Anticoagulants Serotonin release by platelets plays an important role in hemostasis. The concurrent use of an antiplatelet agent or anticoagulant with vilazodone hydrochloride may potentiate the risk of bleeding. Inform patients of the increased risk of bleeding with the concomitant use of vilazodone hydrochloride and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio (INR) when initiating, titrating, or discontinuing vilazodone hydrochloride [see Warnings and Precautions ( 5.3 )] . Strong CYP3A4 Inhibitors (e.g., itraconazole, clarithromycin, voriconazole) The concomitant use of vilazodone hydrochloride and strong CYP3A4 inhibitors increased the exposure of vilazodone compared to the use of vilazodone hydrochloride alone [see Clinical Pharmacology ( 12.3 )] . The vilazodone hydrochloride dose should not exceed 20 mg once daily with the concomitant use of a strong CYP3A4 inhibitor [see Dosage and Administration ( 2.4 ), Clinical Pharmacology ( 12.3 )] . Strong CYP3A4 Inducers (e.g., carbamazepine, phenytoin, rifampin) The concomitant use of vilazodone hydrochloride and strong CYP3A4 inducers decreased the exposure of vilazodone compared to the use of vilazodone hydrochloride alone [see Clinical Pharmacology ( 12.3 )] . Based on clinical response, consider increasing the dosage of vilazodone hydrochloride, over 1 to 2 weeks in patients taking strong CYP3A4 inducers for greater than 14 days [see Dosage and Administration ( 2.4 ), Clinical Pharmacology ( 12.3 )] . Digoxin Digoxin is a narrow therapeutic index drug. Concomitant use of vilazodone hydrochloride increased digoxin concentrations [see Clinical Pharmacology ( 12.3 )] . Measure serum digoxin concentrations before initiating concomitant use of vilazodone hydrochloride.

istration ( 2.4 ), Clinical Pharmacology ( 12.3 )] . Digoxin Digoxin is a narrow therapeutic index drug. Concomitant use of vilazodone hydrochloride increased digoxin concentrations [see Clinical Pharmacology ( 12.3 )] . Measure serum digoxin concentrations before initiating concomitant use of vilazodone hydrochloride. Continue monitoring and reduce digoxin dose as necessary. 7.2 Drugs Having No Clinically Important Interactions with Vilazodone Hydrochloride Based on pharmacokinetic studies, no dosage adjustment is required for drugs that are substrates of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and/or P-glycoprotein (except narrow therapeutic index drugs, e.g., digoxin), when vilazodone hydrochloride is administered concomitantly [see Drug Interactions ( 7.1 ), Clinical Pharmacology ( 12.3 )] .

<table width="1000px" cellspacing="0" cellpadding="4" border="1"><caption>Table 4: Clinically Important Drug Interactions with Vilazodone Hydrochloride</caption><col width="1pt"/><col width="2.55in"/><col width="2.55in"/><tbody><tr><td><paragraph><content styleCode="bold">Concomitant Drug Name or Drug Class</content></paragraph></td><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Clinical Rationale</content></paragraph></td><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Clinical Recommendation</content></paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Monoamine Oxidase Inhibitors (MAOIs)</paragraph></td><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>The concomitant use of MAOIs and serotonergic drugs including vilazodone hydrochloride increases the risk of serotonin syndrome.</paragraph></td><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Vilazodone hydrochloride is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue <content styleCode="italics">[see Contraindications ( <linkHtml href="#www.splportal.comLINK_28e66f97-39e2-493a-bde5-03b3b8b399ba">4</linkHtml>), Dosage and Administration ( <linkHtml href="#www.splportal.comLINK_9f85643e-7c17-4672-be7b-618afba782c2">2.3</linkHtml>), and Warnings and Precautions ( <linkHtml href="#www.splportal.comLINK_c4728821-ba75-41a7-9e5c-9ae4ae9d51fd">5.2</linkHtml>)] </content>. </paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Other Serotonergic Drugs</paragraph></td><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Concomitant use of vilazodone hydrochloride with other serotonergic drugs (including other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, buspirone, amphetamines, tryptophan, and St. John&#x2019;s Wort) increases the risk of serotonin syndrome.</paragraph></td><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Monitor patients for signs and symptoms of serotonin syndrome, particularly during vilazodone hydrochloride initiation. If serotonin syndrome occurs, consider discontinuation of vilazodone hydrochloride and/or concomitant serotonergic drugs <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#www.splportal.comLINK_c4728821-ba75-41a7-9e5c-9ae4ae9d51fd">5.2</linkHtml>)] </content>. </paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Antiplatelet Agents and Anticoagulants</paragraph></td><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Serotonin release by platelets plays an important role in hemostasis. The concurrent use of an antiplatelet agent or anticoagulant with vilazodone hydrochloride may potentiate the risk of bleeding.</paragraph></td><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Inform patients of the increased risk of bleeding with the concomitant use of vilazodone hydrochloride and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio (INR) when initiating, titrating, or discontinuing vilazodone hydrochloride <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#www.splportal.comLINK_07bdecac-1f2b-46ce-9890-ff15264ee1b5">5.3</linkHtml>)] </content>.

atients taking warfarin, carefully monitor the international normalized ratio (INR) when initiating, titrating, or discontinuing vilazodone hydrochloride <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#www.splportal.comLINK_07bdecac-1f2b-46ce-9890-ff15264ee1b5">5.3</linkHtml>)] </content>. </paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Strong CYP3A4 Inhibitors (e.g., itraconazole, clarithromycin, voriconazole)</paragraph></td><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>The concomitant use of vilazodone hydrochloride and strong CYP3A4 inhibitors increased the exposure of vilazodone compared to the use of vilazodone hydrochloride alone <content styleCode="italics">[see Clinical Pharmacology ( <linkHtml href="#www.splportal.comLINK_2918cb2b-1703-46cc-9d3e-43426ca8d455">12.3</linkHtml>)] </content>. </paragraph></td><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>The vilazodone hydrochloride dose should not exceed 20 mg once daily with the concomitant use of a strong CYP3A4 inhibitor <content styleCode="italics">[see Dosage and Administration ( <linkHtml href="#www.splportal.comLINK_020872f1-393c-4524-93a7-0938919c1fc4">2.4</linkHtml>), Clinical Pharmacology ( <linkHtml href="#www.splportal.comLINK_2918cb2b-1703-46cc-9d3e-43426ca8d455">12.3</linkHtml>)] </content>. </paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Strong CYP3A4</paragraph><paragraph>Inducers (e.g., carbamazepine, phenytoin, rifampin)</paragraph></td><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>The concomitant use of vilazodone hydrochloride and strong CYP3A4 inducers decreased the exposure of vilazodone compared to the use of vilazodone hydrochloride alone <content styleCode="italics">[see Clinical Pharmacology ( <linkHtml href="#www.splportal.comLINK_2918cb2b-1703-46cc-9d3e-43426ca8d455">12.3</linkHtml>)] </content>. </paragraph></td><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Based on clinical response, consider increasing the dosage of vilazodone hydrochloride, over 1 to 2 weeks in patients taking strong CYP3A4 inducers for greater than 14 days <content styleCode="italics">[see Dosage and Administration ( <linkHtml href="#www.splportal.comLINK_020872f1-393c-4524-93a7-0938919c1fc4">2.4</linkHtml>), Clinical Pharmacology ( <linkHtml href="#www.splportal.comLINK_2918cb2b-1703-46cc-9d3e-43426ca8d455">12.3</linkHtml>)] </content>. </paragraph></td></tr><tr><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Digoxin</paragraph></td><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Digoxin is a narrow therapeutic index drug. Concomitant use of vilazodone hydrochloride increased digoxin concentrations <content styleCode="italics">[see Clinical Pharmacology ( <linkHtml href="#www.splportal.comLINK_2918cb2b-1703-46cc-9d3e-43426ca8d455">12.3</linkHtml>)] </content>. </paragraph></td><td styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Measure serum digoxin concentrations before initiating concomitant use of vilazodone hydrochloride. Continue monitoring and reduce digoxin dose as necessary.</paragraph></td></tr></tbody></table>

8 USE IN SPECIFIC POPULATIONS Pregnancy: Third trimester use may increase risk for persistent pulmonary hypertension and withdrawal in the newborn. ( 8.1 ) 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 advise patients to register by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/research/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 ( 5.3 ) and Clinical Considerations] . There are no adequate and well-controlled studies of vilazodone hydrochloride in pregnant women. The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. In animal reproduction studies, oral administration of vilazodone during the period of organogenesis at doses up to 48 and 17 times the maximum recommended human dose (MRHD) in rats and rabbits, respectively, resulted in decreased fetal body weight gain and delayed skeletal ossification but no teratogenic effects were observed. Decreased fetal body weight and delayed skeletal ossification were not observed at doses up to 10 and 4 times the MRHD in rats and rabbits, respectively [see Data] . Clinical Considerations Disease-associated maternal and/or embryo/fetal risk A prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. The women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants. Consider the risks of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. Maternal Adverse Reactions Use of vilazodone hydrochloride in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions ( 5.3 )] . Fetal/Neonatal adverse reactions Exposure to SSRIs and SNRIs, including vilazodone hydrochloride, in late pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding, and/or persistent pulmonary hypertension of the newborn (PPHN). Monitor neonates who were exposed to vilazodone hydrochloride in the third trimester of pregnancy for PPHN and drug discontinuation syndrome [see Data] . Data Human Data Third Trimester Exposure Neonates exposed to SSRIs or SNRIs late in the third trimester, have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. These findings are based on postmarketing reports. Such complications can arise immediately upon delivery.

] . Data Human Data Third Trimester Exposure Neonates exposed to SSRIs or SNRIs late in the third trimester, have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. These findings are based on postmarketing reports. 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, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. In some cases, the clinical picture was consistent with serotonin syndrome [see Warnings and Precautions ( 5.2 )] . Exposure during late pregnancy to SSRIs may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in 1 to 2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. In a retrospective case-control study of 377 women whose infants were born with PPHN and 836 women whose infants were born healthy, the risk for developing PPHN was approximately six-fold higher for infants exposed to SSRIs after the 20th week of gestation compared to infants who had not been exposed to antidepressants during pregnancy. A study of 831,324 infants born in Sweden in 1997 to 2005 found a PPHN risk ratio of 2.4 (95% CI 1.2 to 4.3) associated with patient-reported maternal use of SSRIs "in early pregnancy" and a PPHN risk ratio of 3.6 (95% CI 1.2 to 8.3) associated with a combination of patient-reported maternal use of SSRIs "in early pregnancy" and an antenatal SSRI prescription "in later pregnancy." Animal Data No teratogenic effects were observed when vilazodone was given to pregnant rats or rabbits during the period of organogenesis at oral doses up to 200 mg/kg/day and 36 mg/kg/day, respectively. These doses are 48 and 17 times, in rats and rabbits, respectively, the maximum recommended human dose (MRHD) of 40 mg on a mg/m 2 basis. Fetal body weight gain was reduced, and skeletal ossification was delayed in both rats and rabbits at these doses; these effects were not observed at doses up to 10 times the MRHD in rats or 4 times the MRHD in rabbits. When vilazodone was administered to pregnant rats at an oral dose of 30 times the MRHD during the period of organogenesis and throughout pregnancy and lactation, the number of live born pups was decreased. There was an increase in early postnatal pup mortality, and among surviving pups there was decreased body weight, delayed maturation, and decreased fertility in adulthood. There was some maternal toxicity at this dose. These effects were not seen at 6 times the MRHD. 8.2 Lactation Risk Summary There are no data on the presence of vilazodone in human milk, the effects of vilazodone on the breastfed infant, or the effects of the drug on milk production. However, vilazodone is excreted in rat milk [see Data] . The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for vilazodone hydrochloride and any potential adverse effects on the breastfed child from vilazodone hydrochloride or from the underlying maternal condition. Data Animal Data Administration of vilazodone to lactating rats at an oral dose of 30 times the maximum recommended human dose (MRHD), resulted in early postnatal pup mortality, and among surviving pups there was decreased body weight and delayed maturation. 8.4 Pediatric Use The safety and effectiveness of vilazodone hydrochloride have not been established in pediatric patients for the treatment of MDD.

imes the maximum recommended human dose (MRHD), resulted in early postnatal pup mortality, and among surviving pups there was decreased body weight and delayed maturation. 8.4 Pediatric Use The safety and effectiveness of vilazodone hydrochloride have not been established in pediatric patients for the treatment of MDD. Efficacy was not demonstrated in two adequate and well controlled, 8-week studies including a total of 1,002 pediatric patients ages 7 years to 17 years of age with MDD. The following adverse reactions were reported in at least 5% of pediatric patients treated with vilazodone hydrochloride and occurred at a rate at least twice that for pediatric patients receiving placebo: nausea, vomiting, diarrhea, abdominal pain/discomfort, and dizziness. Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients [see Boxed Warning, Warnings and Precautions ( 5.1 ), and Adverse Reactions ( 6.2 )] . Juvenile Animal Toxicity Data In a juvenile animal study, male and female rats were treated with vilazodone (10 mg/kg/day, 50 mg/kg/day, and 200 mg/kg/day) starting on postnatal day (PND) 21 through 90. A delay in the age of attainment of vaginal patency (i.e. sexual maturation) was observed in females starting at 50 mg/kg/day with a No Observed Adverse Effect Level (NOAEL) of 10 mg/kg/day. This NOAEL was associated with AUC levels similar to those measured at a maximum dose tested in pediatrics (30 mg). Adverse behavioral effects (lack of habituation in an acoustic startle test) were observed in males at 200 mg/kg and females starting at 50 mg/kg both during drug treatment and the recovery periods. The NOAEL for this finding was 50 mg/kg for males and 10 mg/kg for females, which was associated with AUC levels greater than (males) or similar (females), to those observed with the maximum dose tested in pediatric patients. An 8% decrease in femur mineral density was observed in female rats at 200 mg/kg, compared to the control group. The NOAEL for this finding was 50 mg/kg, which was associated with an AUC level greater than those measured at the maximum dose tested in pediatrics. 8.5 Geriatric Use Based on a pharmacokinetic study, no dosage adjustment of vilazodone hydrochloride is recommended on the basis of age (see Figure 3). Results from pharmacokinetic study of a single 20 mg vilazodone hydrochloride dose in geriatric subjects (>65 years-old) vs. younger subjects (24 to 55 years-old) demonstrated that the pharmacokinetics were generally similar between the two age groups [see Clinical Pharmacology ( 12.3 )] . Clinical studies of vilazodone hydrochloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Of the 3,007 patients in clinical studies with vilazodone hydrochloride, 65 (2.2%) were 65 years of age or older, and 378 (12.6%) were 55 to 64 years of age. In general, dose selection for an elderly patient should be conservative, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Serotonergic antidepressants 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 ( 5.8 )] . No other differences in adverse reactions were observed between geriatric and younger patients.

therapy. Serotonergic antidepressants 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 ( 5.8 )] . No other differences in adverse reactions were observed between geriatric and younger patients. 8.6 Use in Other Patient Populations No dosage adjustment of vilazodone hydrochloride is necessary on the basis of gender, renal function (mild to severe renal impairment, glomerular filtration rate: 15 to 90 mL/minute), or hepatic function (mild to severe hepatic impairment, Child-Pugh score: 5 to 15 [see 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 advise patients to register by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/research/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 ( 5.3 ) and Clinical Considerations] . There are no adequate and well-controlled studies of vilazodone hydrochloride in pregnant women. The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. In animal reproduction studies, oral administration of vilazodone during the period of organogenesis at doses up to 48 and 17 times the maximum recommended human dose (MRHD) in rats and rabbits, respectively, resulted in decreased fetal body weight gain and delayed skeletal ossification but no teratogenic effects were observed. Decreased fetal body weight and delayed skeletal ossification were not observed at doses up to 10 and 4 times the MRHD in rats and rabbits, respectively [see Data] . Clinical Considerations Disease-associated maternal and/or embryo/fetal risk A prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. The women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants. Consider the risks of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. Maternal Adverse Reactions Use of vilazodone hydrochloride in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions ( 5.3 )] . Fetal/Neonatal adverse reactions Exposure to SSRIs and SNRIs, including vilazodone hydrochloride, in late pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding, and/or persistent pulmonary hypertension of the newborn (PPHN). Monitor neonates who were exposed to vilazodone hydrochloride in the third trimester of pregnancy for PPHN and drug discontinuation syndrome [see Data] . Data Human Data Third Trimester Exposure Neonates exposed to SSRIs or SNRIs late in the third trimester, have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. These findings are based on postmarketing reports. 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, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome.

cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. In some cases, the clinical picture was consistent with serotonin syndrome [see Warnings and Precautions ( 5.2 )] . Exposure during late pregnancy to SSRIs may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in 1 to 2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. In a retrospective case-control study of 377 women whose infants were born with PPHN and 836 women whose infants were born healthy, the risk for developing PPHN was approximately six-fold higher for infants exposed to SSRIs after the 20th week of gestation compared to infants who had not been exposed to antidepressants during pregnancy. A study of 831,324 infants born in Sweden in 1997 to 2005 found a PPHN risk ratio of 2.4 (95% CI 1.2 to 4.3) associated with patient-reported maternal use of SSRIs "in early pregnancy" and a PPHN risk ratio of 3.6 (95% CI 1.2 to 8.3) associated with a combination of patient-reported maternal use of SSRIs "in early pregnancy" and an antenatal SSRI prescription "in later pregnancy." Animal Data No teratogenic effects were observed when vilazodone was given to pregnant rats or rabbits during the period of organogenesis at oral doses up to 200 mg/kg/day and 36 mg/kg/day, respectively. These doses are 48 and 17 times, in rats and rabbits, respectively, the maximum recommended human dose (MRHD) of 40 mg on a mg/m 2 basis. Fetal body weight gain was reduced, and skeletal ossification was delayed in both rats and rabbits at these doses; these effects were not observed at doses up to 10 times the MRHD in rats or 4 times the MRHD in rabbits. When vilazodone was administered to pregnant rats at an oral dose of 30 times the MRHD during the period of organogenesis and throughout pregnancy and lactation, the number of live born pups was decreased. There was an increase in early postnatal pup mortality, and among surviving pups there was decreased body weight, delayed maturation, and decreased fertility in adulthood. There was some maternal toxicity at this dose. These effects were not seen at 6 times the MRHD.

8.2 Lactation Risk Summary There are no data on the presence of vilazodone in human milk, the effects of vilazodone on the breastfed infant, or the effects of the drug on milk production. However, vilazodone is excreted in rat milk [see Data] . The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for vilazodone hydrochloride and any potential adverse effects on the breastfed child from vilazodone hydrochloride or from the underlying maternal condition. Data Animal Data Administration of vilazodone to lactating rats at an oral dose of 30 times the maximum recommended human dose (MRHD), resulted in early postnatal pup mortality, and among surviving pups there was decreased body weight and delayed maturation.

8.4 Pediatric Use The safety and effectiveness of vilazodone hydrochloride have not been established in pediatric patients for the treatment of MDD. Efficacy was not demonstrated in two adequate and well controlled, 8-week studies including a total of 1,002 pediatric patients ages 7 years to 17 years of age with MDD. The following adverse reactions were reported in at least 5% of pediatric patients treated with vilazodone hydrochloride and occurred at a rate at least twice that for pediatric patients receiving placebo: nausea, vomiting, diarrhea, abdominal pain/discomfort, and dizziness. Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients [see Boxed Warning, Warnings and Precautions ( 5.1 ), and Adverse Reactions ( 6.2 )] . Juvenile Animal Toxicity Data In a juvenile animal study, male and female rats were treated with vilazodone (10 mg/kg/day, 50 mg/kg/day, and 200 mg/kg/day) starting on postnatal day (PND) 21 through 90. A delay in the age of attainment of vaginal patency (i.e. sexual maturation) was observed in females starting at 50 mg/kg/day with a No Observed Adverse Effect Level (NOAEL) of 10 mg/kg/day. This NOAEL was associated with AUC levels similar to those measured at a maximum dose tested in pediatrics (30 mg). Adverse behavioral effects (lack of habituation in an acoustic startle test) were observed in males at 200 mg/kg and females starting at 50 mg/kg both during drug treatment and the recovery periods. The NOAEL for this finding was 50 mg/kg for males and 10 mg/kg for females, which was associated with AUC levels greater than (males) or similar (females), to those observed with the maximum dose tested in pediatric patients. An 8% decrease in femur mineral density was observed in female rats at 200 mg/kg, compared to the control group. The NOAEL for this finding was 50 mg/kg, which was associated with an AUC level greater than those measured at the maximum dose tested in pediatrics.

8.5 Geriatric Use Based on a pharmacokinetic study, no dosage adjustment of vilazodone hydrochloride is recommended on the basis of age (see Figure 3). Results from pharmacokinetic study of a single 20 mg vilazodone hydrochloride dose in geriatric subjects (>65 years-old) vs. younger subjects (24 to 55 years-old) demonstrated that the pharmacokinetics were generally similar between the two age groups [see Clinical Pharmacology ( 12.3 )] . Clinical studies of vilazodone hydrochloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Of the 3,007 patients in clinical studies with vilazodone hydrochloride, 65 (2.2%) were 65 years of age or older, and 378 (12.6%) were 55 to 64 years of age. In general, dose selection for an elderly patient should be conservative, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Serotonergic antidepressants 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 ( 5.8 )] . No other differences in adverse reactions were observed between geriatric and younger patients.

9 DRUG ABUSE AND DEPENDENCE 9.1 Controlled Substance Vilazodone hydrochloride is not a controlled substance. 9.2 Abuse and Dependence Vilazodone hydrochloride has been systematically studied in animals and did not demonstrate abuse or dependence potential. While vilazodone hydrochloride has not been systematically studied in humans for its potential for abuse, there was no suggested evidence of drug-seeking behavior in the clinical studies.

10 OVERDOSAGE There is limited clinical trial experience regarding human overdose with vilazodone hydrochloride. The adverse reactions associated with overdose of vilazodone hydrochloride at doses of 200 mg to 280 mg (5 to 7 times the recommended dosage) as observed in clinical trials included serotonin syndrome, lethargy, restlessness, hallucinations, and disorientation. For current information on the management of poisoning or overdose, contact a poison control center at 1-800-222-1222. No specific antidotes for vilazodone are known. Removal of vilazodone by dialysis has not been studied; however, the high volume of distribution of vilazodone suggests that dialysis will not be effective in reducing vilazodone plasma concentrations.

11 DESCRIPTION Vilazodone hydrochloride tablets for oral administration contain polymorph Form IV vilazodone hydrochloride (HCl), a selective serotonin reuptake inhibitor and a 5HT 1A receptor partial agonist. Vilazodone HCl is 2-benzofurancarboxamide, 5-[4-[4-(5-cyano-1 H -indol-3-yl)butyl]-1-piperazinyl]-, hydrochloride (1:1). It has a molecular formula C 26 H 27 N 5 O 2 . HCl and its molecular weight is 477.99. The structural formula is: Vilazodone hydrochloride tablets are available as 10 mg, 20 mg, and 40 mg film-coated tablets containing 10 mg, 20 mg, and 40 mg of vilazodone HCl, respectively. In addition to the active ingredient, vilazodone hydrochloride tablets contain the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol 3350, polyvinyl alcohol – part hydrolyzed, talc and titanium dioxide. Additionally, the 10 mg tablets contain iron oxide red, the 20 mg tablets contain iron oxide red and iron oxide yellow, and the 40 mg tablets contain FD&C Blue #2/indigo carmine aluminum lake. formula

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The mechanism of action of vilazodone in the treatment of major depressive disorder is not fully understood, but is thought to be related to its enhancement of serotonergic activity in the CNS through selective inhibition of serotonin reuptake. Vilazodone is also a partial agonist at serotonergic 5-HT 1A receptors; however, the net result of this action on serotonergic transmission and its role in vilazodone’s antidepressant effect are unknown. 12.2 Pharmacodynamics Vilazodone binds with high affinity to the serotonin reuptake site (Ki= 0.1 nM), but not to the norepinephrine (Ki=56 nM) or dopamine (Ki=37 nM) reuptake sites. Vilazodone potently and selectively inhibits reuptake of serotonin (IC 50 =1.6 nM). Vilazodone also binds selectively with high affinity to 5-HT 1A receptors (IC 50 =2.1 nM) and is a 5-HT 1A receptor partial agonist. Cardiac Electrophysiology Treatment with vilazodone hydrochloride did not prolong the QTc interval. The effect of vilazodone hydrochloride [20 mg, 40 mg, 60 mg, and 80 mg (2 times the recommended dosage)] on the QTc interval was evaluated in a randomized, placebo-, and active-controlled (moxifloxacin 400 mg), parallel-group, thorough QTc study in 157 healthy subjects. The study demonstrated an ability to detect small effects. The upper bound of the 90% confidence interval for the largest placebo-adjusted, baseline-corrected QTc interval was below 10 msec, based on the individual correction method (QTcI). Thus, at doses of 2 times the recommended dosage, vilazodone hydrochloride did not prolong the QTc interval to a clinically relevant extent. 12.3 Pharmacokinetics Vilazodone activity is due primarily to the parent drug. The pharmacokinetics of vilazodone (5 mg to 80 mg) are dose-proportional. Accumulation of vilazodone after administration of single vilazodone hydrochloride doses did not vary with dose, and steady-state was achieved in about 3 days. Elimination of vilazodone is primarily by hepatic metabolism with a terminal half-life of approximately 25 hours. At steady-state, after daily dosing of vilazodone hydrochloride 40 mg under fed conditions, the mean C max value was 156 ng/mL, and the mean AUC ( 0-24 hours ) value was 1645 ng·h/mL. Absorption Vilazodone concentrations peaked at a median of 4-5 hours (T max ) after vilazodone hydrochloride administration and declined with a terminal half-life of approximately 25 hours. The absolute bioavailability of vilazodone was 72% with food. Vilazodone AUC and C max in the fasted state can be decreased by approximately 50% and 60%, respectively, compared to the fed state. Administration without food can result in inadequate drug concentrations and may reduce effectiveness. Coadministration of vilazodone hydrochloride with ethanol or with a proton pump inhibitor (pantoprazole) did not affect the rate or extent of vilazodone absorption. In addition, neither the T max nor terminal elimination rate of vilazodone was altered by coadministration with either pantoprazole or ethanol. Absorption is decreased by approximately 25% if vomiting occurs within 7 hours of ingestion; no replacement dose is needed. Distribution Vilazodone is widely distributed and approximately 96% to 99% protein-bound. Administration of vilazodone hydrochloride to a patient taking another drug that is highly protein bound may cause increased free concentrations of the other drug, because vilazodone is highly bound to plasma protein.

e is needed. Distribution Vilazodone is widely distributed and approximately 96% to 99% protein-bound. Administration of vilazodone hydrochloride to a patient taking another drug that is highly protein bound may cause increased free concentrations of the other drug, because vilazodone is highly bound to plasma protein. The interaction between vilazodone and other highly protein-bound drugs has not been evaluated. Metabolism and Elimination Vilazodone hydrochloride is extensively metabolized through CYP and non-CYP pathways (possibly by carboxylesterase), with only 1% of the dose recovered in the urine and 2% of the dose recovered in the feces as unchanged vilazodone. CYP3A4 is primarily responsible for its metabolism among CYP pathways, with minor contributions from CYP2C19 and CYP2D6. Drug Interaction Studies Figure 1 below includes the impact of other drugs on the pharmacokinetics of vilazodone [see Drug Interactions ( 7 )]. Figure 1. Effect of Other Drugs on Vilazodone Pharmacokinetics In vitro studies indicate that vilazodone is unlikely to inhibit or induce the metabolism of substrates for CYP1A1, 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4 or 3A5, except for CYP2C8. The effect of vilazodone on CYP2C8 activity has not been tested in vivo . Figure 2 below includes the impact of vilazodone on the pharmacokinetics of other drugs in vivo . Figure 2. Impact of Vilazodone on Other Drug Pharmacokinetics AUCp = area under plasma concentration-time curve of nifedipine; CRmp = plasma concentration ratio of paraxanthine vs caffeine at 8 hours; URmp = urinary recovery ratio of 4-OH-debrisoquine vs debrisoquine; CLrm = renal clearance of 4′-OH-flurbiprofen; Um = urinary recovery of 4′-OH-mephenytoin; C max = maximal plasma concentration of digoxin; AUC = area under concentration-time curve of digoxin; P-gp = P-glycoprotein. Studies in Specific Populations: The presence of mild to severe renal impairment or mild to severe hepatic impairment did not affect the apparent clearance of vilazodone (see Figure 3). There were no pharmacokinetic differences of vilazodone in geriatric patients compared to younger patients, or between males and females (see Figure 3). Figure 3: Impact of Intrinsic Factors on Vilazodone Pharmacokinetics The data shown for elderly subjects (>65 years) are relative to younger subjects (24 to 55 years). The data shown for female subjects are relative to male subjects. The data shown for renal and hepatic impairment are relative to subjects with normal renal and hepatic function, respectively. fig1 fig2 fig3

12.1 Mechanism of Action The mechanism of action of vilazodone in the treatment of major depressive disorder is not fully understood, but is thought to be related to its enhancement of serotonergic activity in the CNS through selective inhibition of serotonin reuptake. Vilazodone is also a partial agonist at serotonergic 5-HT 1A receptors; however, the net result of this action on serotonergic transmission and its role in vilazodone’s antidepressant effect are unknown.

12.2 Pharmacodynamics Vilazodone binds with high affinity to the serotonin reuptake site (Ki= 0.1 nM), but not to the norepinephrine (Ki=56 nM) or dopamine (Ki=37 nM) reuptake sites. Vilazodone potently and selectively inhibits reuptake of serotonin (IC 50 =1.6 nM). Vilazodone also binds selectively with high affinity to 5-HT 1A receptors (IC 50 =2.1 nM) and is a 5-HT 1A receptor partial agonist. Cardiac Electrophysiology Treatment with vilazodone hydrochloride did not prolong the QTc interval. The effect of vilazodone hydrochloride [20 mg, 40 mg, 60 mg, and 80 mg (2 times the recommended dosage)] on the QTc interval was evaluated in a randomized, placebo-, and active-controlled (moxifloxacin 400 mg), parallel-group, thorough QTc study in 157 healthy subjects. The study demonstrated an ability to detect small effects. The upper bound of the 90% confidence interval for the largest placebo-adjusted, baseline-corrected QTc interval was below 10 msec, based on the individual correction method (QTcI). Thus, at doses of 2 times the recommended dosage, vilazodone hydrochloride did not prolong the QTc interval to a clinically relevant extent.

12.3 Pharmacokinetics Vilazodone activity is due primarily to the parent drug. The pharmacokinetics of vilazodone (5 mg to 80 mg) are dose-proportional. Accumulation of vilazodone after administration of single vilazodone hydrochloride doses did not vary with dose, and steady-state was achieved in about 3 days. Elimination of vilazodone is primarily by hepatic metabolism with a terminal half-life of approximately 25 hours. At steady-state, after daily dosing of vilazodone hydrochloride 40 mg under fed conditions, the mean C max value was 156 ng/mL, and the mean AUC ( 0-24 hours ) value was 1645 ng·h/mL. Absorption Vilazodone concentrations peaked at a median of 4-5 hours (T max ) after vilazodone hydrochloride administration and declined with a terminal half-life of approximately 25 hours. The absolute bioavailability of vilazodone was 72% with food. Vilazodone AUC and C max in the fasted state can be decreased by approximately 50% and 60%, respectively, compared to the fed state. Administration without food can result in inadequate drug concentrations and may reduce effectiveness. Coadministration of vilazodone hydrochloride with ethanol or with a proton pump inhibitor (pantoprazole) did not affect the rate or extent of vilazodone absorption. In addition, neither the T max nor terminal elimination rate of vilazodone was altered by coadministration with either pantoprazole or ethanol. Absorption is decreased by approximately 25% if vomiting occurs within 7 hours of ingestion; no replacement dose is needed. Distribution Vilazodone is widely distributed and approximately 96% to 99% protein-bound. Administration of vilazodone hydrochloride to a patient taking another drug that is highly protein bound may cause increased free concentrations of the other drug, because vilazodone is highly bound to plasma protein. The interaction between vilazodone and other highly protein-bound drugs has not been evaluated. Metabolism and Elimination Vilazodone hydrochloride is extensively metabolized through CYP and non-CYP pathways (possibly by carboxylesterase), with only 1% of the dose recovered in the urine and 2% of the dose recovered in the feces as unchanged vilazodone. CYP3A4 is primarily responsible for its metabolism among CYP pathways, with minor contributions from CYP2C19 and CYP2D6. Drug Interaction Studies Figure 1 below includes the impact of other drugs on the pharmacokinetics of vilazodone [see Drug Interactions ( 7 )]. Figure 1. Effect of Other Drugs on Vilazodone Pharmacokinetics In vitro studies indicate that vilazodone is unlikely to inhibit or induce the metabolism of substrates for CYP1A1, 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4 or 3A5, except for CYP2C8. The effect of vilazodone on CYP2C8 activity has not been tested in vivo . Figure 2 below includes the impact of vilazodone on the pharmacokinetics of other drugs in vivo . Figure 2. Impact of Vilazodone on Other Drug Pharmacokinetics AUCp = area under plasma concentration-time curve of nifedipine; CRmp = plasma concentration ratio of paraxanthine vs caffeine at 8 hours; URmp = urinary recovery ratio of 4-OH-debrisoquine vs debrisoquine; CLrm = renal clearance of 4′-OH-flurbiprofen; Um = urinary recovery of 4′-OH-mephenytoin; C max = maximal plasma concentration of digoxin; AUC = area under concentration-time curve of digoxin; P-gp = P-glycoprotein.

paraxanthine vs caffeine at 8 hours; URmp = urinary recovery ratio of 4-OH-debrisoquine vs debrisoquine; CLrm = renal clearance of 4′-OH-flurbiprofen; Um = urinary recovery of 4′-OH-mephenytoin; C max = maximal plasma concentration of digoxin; AUC = area under concentration-time curve of digoxin; P-gp = P-glycoprotein. Studies in Specific Populations: The presence of mild to severe renal impairment or mild to severe hepatic impairment did not affect the apparent clearance of vilazodone (see Figure 3). There were no pharmacokinetic differences of vilazodone in geriatric patients compared to younger patients, or between males and females (see Figure 3). Figure 3: Impact of Intrinsic Factors on Vilazodone Pharmacokinetics The data shown for elderly subjects (>65 years) are relative to younger subjects (24 to 55 years). The data shown for female subjects are relative to male subjects. The data shown for renal and hepatic impairment are relative to subjects with normal renal and hepatic function, respectively. fig1 fig2 fig3

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Carcinogenicity studies were conducted in which B6C3F1mice and Wistar rats were given oral doses of vilazodone up to 135 mg/kg/day and 150 mg/kg/day, respectively, for 2 years. These doses are approximately 16.5 and 36 times the maximum recommended human dose (MRHD) of 40 mg, respectively, on a mg/m 2 basis. In mice, the incidence of hepatocellular carcinomas was increased in males at 16.5 times the MRHD; this finding was not observed at 5.5 times the MRHD. The incidence of malignant mammary gland tumors was numerically increased in females at 5.5 and 16.5 times the MRHD, with statistical significance at 16.5 the MRHD; this finding was not observed at 1.8 times the MRHD. Elevated prolactin levels were observed in a 2-week study of vilazodone administered at 5.5 and 33 times the MRHD. Increases in prolactin levels are known to cause mammary tumors in rodents. In the rat study, vilazodone was not carcinogenic in either sex at doses up to 36 times the MRHD. Mutagenesis Vilazodone was not mutagenic in the in vitro bacterial reverse mutation assay (Ames test). Vilazodone was negative in the in vitro V79/HGRPT mammalian cell forward mutation assay. Vilazodone was clastogenic in two in vitro mammalian cell chromosome aberration assays. However, vilazodone was negative for clastogenic activity in both an in vivo rat bone marrow chromosome aberration assay and a micronucleus test. Vilazodone was also negative in an in vivo / in vitro unscheduled DNA synthesis assay in rats. Impairment of Fertility Treatment of rats with vilazodone at a dose of 125 mg/kg, which is 30 times the MRHD of 40 mg on a mg/m 2 basis, caused impairment of male fertility with no effect on female fertility. Impaired male fertility was not observed at 6 times the MRHD.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Carcinogenicity studies were conducted in which B6C3F1mice and Wistar rats were given oral doses of vilazodone up to 135 mg/kg/day and 150 mg/kg/day, respectively, for 2 years. These doses are approximately 16.5 and 36 times the maximum recommended human dose (MRHD) of 40 mg, respectively, on a mg/m 2 basis. In mice, the incidence of hepatocellular carcinomas was increased in males at 16.5 times the MRHD; this finding was not observed at 5.5 times the MRHD. The incidence of malignant mammary gland tumors was numerically increased in females at 5.5 and 16.5 times the MRHD, with statistical significance at 16.5 the MRHD; this finding was not observed at 1.8 times the MRHD. Elevated prolactin levels were observed in a 2-week study of vilazodone administered at 5.5 and 33 times the MRHD. Increases in prolactin levels are known to cause mammary tumors in rodents. In the rat study, vilazodone was not carcinogenic in either sex at doses up to 36 times the MRHD. Mutagenesis Vilazodone was not mutagenic in the in vitro bacterial reverse mutation assay (Ames test). Vilazodone was negative in the in vitro V79/HGRPT mammalian cell forward mutation assay. Vilazodone was clastogenic in two in vitro mammalian cell chromosome aberration assays. However, vilazodone was negative for clastogenic activity in both an in vivo rat bone marrow chromosome aberration assay and a micronucleus test. Vilazodone was also negative in an in vivo / in vitro unscheduled DNA synthesis assay in rats. Impairment of Fertility Treatment of rats with vilazodone at a dose of 125 mg/kg, which is 30 times the MRHD of 40 mg on a mg/m 2 basis, caused impairment of male fertility with no effect on female fertility. Impaired male fertility was not observed at 6 times the MRHD.

14 CLINICAL STUDIES The efficacy of vilazodone hydrochloride as a treatment for major depressive disorder was demonstrated in four multicenter, randomized, double-blind, placebo-controlled studies in adult (18 to 70 years of age) outpatients who met the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria for MDD. Three 8-week studies evaluated the efficacy of vilazodone hydrochloride tablets 40 mg (Studies 1 to 3) and one 10-week study (Study 4) evaluated the efficacy of vilazodone hydrochloride tablets 20 mg and 40 mg (see Table 5). In these studies, patients were randomized to either 20 mg or 40 mg, or placebo once daily with food. Patients were either titrated over 1week to a dose of 20 mg daily or over 2 weeks to a dose of 40 mg once daily of vilazodone hydrochloride tablets with food. Vilazodone hydrochloride was superior to placebo in the improvement of depressive symptoms as measured by the change from baseline to endpoint visit in the Montgomery-Asberg Depression Rating Scale (MADRS) total score for both doses. The MADRS is a ten-item, clinician-rated scale used to assess severity of depressive symptoms. Scores on the MADRS range from 0 to 60, with higher scores indicating more severe depression. Clinical Global Impression - Severity (CGI-S) was evaluated in Studies 3 and 4. Vilazodone hydrochloride tablets 20 mg and 40 mg demonstrated superiority over placebo as measured by improvement in CGI-S score. Table 5: Summary of Results for the Primary Efficacy Endpoint - MADRS Total Score Study Number Treatment Group Number of Patients a Mean Baseline Score (SD) LS Mean Change from Baseline (SE) Placebo-subtracted Difference b (95% CI) Study 1 Vilazodone Hydrochloride 40 mg/day 198 30.8 (3.90) -12.9 (0.77) -3.2 (-5.2, -1.3) Placebo 199 30.7 (3.93) -9.6 (0.76) Study 2 Vilazodone Hydrochloride 40 mg/day 231 31.9 (3.50) -13.3 (0.90) -2.5 (-4.4, -0.6) Placebo 232 32.0 (3.63) -10.8 (0.90) Study 3 Vilazodone Hydrochloride 40 mg/day 253 30.7 (3.3) -16.1 (0.64) -5.1 (-6.9, -3.3) Placebo 252 30.9 (3.3) -11.0 (0.65) Study 4 Vilazodone Hydrochloride 20 mg/day * 288 31.3 (3.5) -17.3 (0.63) -2.6 (-4.3, -0.8) Vilazodone Hydrochloride 40 mg/day * 284 31.2 (3.8) -17.6 (0.65) -2.8 (-4.6, -1.1) Placebo 281 31.4 (3.8) -14.8 (0.62) SD = standard deviation; SE = standard error; LS Mean = least-square mean; CI = confidence interval a based on patients who took study medication and had baseline and postbaseline MADRS assessments b difference (drug minus placebo) in least-square mean change from baseline to endpoint * All vilazodone hydrochloride treatment dose groups remained statistically significant compared with placebo after adjusting for multiplicity Baseline demographics information were generally similar across all treatment groups. Examination of population subgroups based on age (there were few patients over 65), gender and race did not reveal any clear evidence of differential responsiveness.

<table width="1000px" cellspacing="0" cellpadding="4"><caption>Table 5: Summary of Results for the Primary Efficacy Endpoint - MADRS Total Score</caption><col width="0.75in"/><col width="1.5in"/><col width="63pt"/><col width="99pt"/><col width="103.5pt"/><col width="117.9pt"/><tbody><tr><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Study</content></paragraph><paragraph><content styleCode="bold">Number</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Treatment Group</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Number of</content></paragraph><paragraph><content styleCode="bold">Patients ^a</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Mean</content></paragraph><paragraph><content styleCode="bold">Baseline Score (SD)</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">LS Mean Change</content></paragraph><paragraph><content styleCode="bold">from Baseline (SE)</content></paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Placebo-subtracted Difference ^b(95% CI) </content></paragraph></td></tr><tr><td align="center" rowspan="2" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Study 1</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Vilazodone Hydrochloride 40 mg/day </paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>198</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>30.8 (3.90)</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>-12.9 (0.77)</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>-3.2 (-5.2, -1.3)</paragraph></td></tr><tr><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Placebo</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>199</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>30.7 (3.93)</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>-9.6 (0.76)</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/></tr><tr><td align="center" rowspan="2" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Study 2</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Vilazodone Hydrochloride</paragraph><paragraph>40 mg/day</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>231</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>31.9 (3.50)</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>-13.3 (0.90)</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>-2.5 (-4.4, -0.6)</paragraph></td></tr><tr><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Placebo</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>232</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>32.0 (3.63)</paragraph></td><td align="center" styleCode=" Bo

r><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Placebo</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>232</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>32.0 (3.63)</paragraph></td><td align="center" styleCode=" Bo trule Toprule Lrule Rrule"><paragraph>-10.8 (0.90)</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/></tr><tr><td align="center" rowspan="2" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Study 3</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Vilazodone Hydrochloride</paragraph><paragraph>40 mg/day</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>253</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>30.7 (3.3)</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>-16.1 (0.64)</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>-5.1 (-6.9, -3.3)</paragraph></td></tr><tr><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Placebo</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>252</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>30.9 (3.3)</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>-11.0 (0.65)</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/></tr><tr><td align="center" rowspan="3" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Study 4</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Vilazodone Hydrochloride</paragraph><paragraph>20 mg/day ^*</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>288</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>31.3 (3.5)</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>-17.3 (0.63)</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>-2.6 (-4.3, -0.8)</paragraph></td></tr><tr><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Vilazodone Hydrochloride</paragraph><paragraph>40 mg/day ^*</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>284</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>31.2 (3.8)</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>-17.6 (0.65)</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>-2.8 (-4.6, -1.1)</paragraph></td></tr><tr><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>Placebo</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>281</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>31.4 (3.8)</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"><paragraph>-14.8 (0.62)</paragraph></td><td align="center" styleCode=" Botrule Toprule Lrule Rrule"/></tr><tr><td colspan="6"><paragraph>SD = standard deviation; SE = standard error; LS Mean = least-square mean; CI = confidence interval</paragraph></td></tr><tr><td colspan="6"><paragraph>^abased on patients who took study medication and had baseline and postbaseline MADRS assessments </paragraph></td></tr><tr><td colspan="6"><paragraph>^bdifference (drug minus placebo) in least-square mean change from baseline to endpoint </paragraph></td></tr><tr><td colspan="6"><paragraph>^*All vilazodone hydrochloride treatment dose groups remained statistical

d postbaseline MADRS assessments </paragraph></td></tr><tr><td colspan="6"><paragraph>^bdifference (drug minus placebo) in least-square mean change from baseline to endpoint </paragraph></td></tr><tr><td colspan="6"><paragraph>^*All vilazodone hydrochloride treatment dose groups remained statistical ly significant compared with placebo after adjusting for multiplicity </paragraph></td></tr></tbody></table>

16 HOW SUPPLIED/STORAGE AND HANDLING Vilazodone hydrochloride tablets are supplied in the following configurations: Tablet Strength Tablet Color/Shape Tablet Markings Package Configuration NDC Code 10 mg pink, oval shaped, film-coated tablet debossed with “TV” on one side and “V7” on the other side Bottle / 30 count 51407-915-30 20 mg beige, oval shaped, film-coated tablet debossed with “TV” on one side and “V71” on the other side Bottle / 30 count 51407-916-30 40 mg blue, oval shaped, film-coated tablet debossed with “TV” on one side and “V72” on the other side Bottle / 30 count 51407-917-30 Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

<table border="1" cellpadding="4" cellspacing="0" width="1000px"><colgroup><col width="1pt"/><col width="1in"/><col width="117pt"/><col width="94.5pt"/><col width="148.5pt"/></colgroup><tbody><tr><td align="center"><paragraph><content styleCode="bold">Tablet Strength</content></paragraph></td><td align="center" styleCode="Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Tablet Color/Shape</content></paragraph></td><td align="center" styleCode="Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Tablet Markings</content></paragraph></td><td align="center" styleCode="Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Package Configuration</content></paragraph></td><td align="center" styleCode="Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">NDC Code</content></paragraph></td></tr><tr><td align="center" styleCode="Botrule Toprule Lrule Rrule"><paragraph>10 mg</paragraph></td><td align="center" styleCode="Botrule Toprule Lrule Rrule"><paragraph>pink, oval shaped, film-coated tablet</paragraph></td><td align="center" styleCode="Botrule Toprule Lrule Rrule"><paragraph>debossed with</paragraph><paragraph>&#x201C;TV&#x201D; on one side and &#x201C;V7&#x201D; on the other side</paragraph></td><td align="center" styleCode="Botrule Toprule Lrule Rrule"><paragraph>Bottle / 30 count</paragraph></td><td align="center" styleCode="Botrule Toprule Lrule Rrule"><paragraph>51407-915-30</paragraph></td></tr><tr><td align="center" styleCode="Botrule Toprule Lrule Rrule"><paragraph>20 mg</paragraph></td><td align="center" styleCode="Botrule Toprule Lrule Rrule"><paragraph>beige, oval shaped, film-coated tablet</paragraph></td><td align="center" styleCode="Botrule Toprule Lrule Rrule"><paragraph>debossed with</paragraph><paragraph>&#x201C;TV&#x201D; on one side and &#x201C;V71&#x201D; on the other side</paragraph></td><td align="center" styleCode="Botrule Toprule Lrule Rrule"><paragraph>Bottle / 30 count</paragraph></td><td align="center" styleCode="Botrule Toprule Lrule Rrule"><paragraph>51407-916-30</paragraph></td></tr><tr><td align="center" styleCode="Botrule Toprule Lrule Rrule"><paragraph>40 mg</paragraph></td><td align="center" styleCode="Botrule Toprule Lrule Rrule"><paragraph>blue, oval shaped, film-coated tablet</paragraph></td><td align="center" styleCode="Botrule Toprule Lrule Rrule"><paragraph>debossed with</paragraph><paragraph>&#x201C;TV&#x201D; on one side and &#x201C;V72&#x201D; on the other side</paragraph></td><td align="center" styleCode="Botrule Toprule Lrule Rrule"><paragraph>Bottle / 30 count</paragraph></td><td align="center" styleCode="Botrule Toprule Lrule Rrule"><paragraph>51407-917-30</paragraph></td></tr></tbody></table>

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 )] . Dosage and Administration Instruct patients to take vilazodone hydrochloride tablets with food and to follow prescribed dosage instructions [see Dosage and Administration ( 2.1 , 2.3 , 2.4 , 2.5 )] . Serotonin Syndrome Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of vilazodone hydrochloride tablets with other serotonergic drugs including triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, and 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). Patients should 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 ) and Drug Interactions ( 7 )] . Increased Risk of Bleeding Inform patients about the concomitant use of vilazodone hydrochloride tablets with aspirin, NSAIDs, other antiplatelet drugs, warfarin, or other anticoagulants because the combined use of drugs that interfere with serotonin reuptake (e.g., vilazodone hydrochloride tablets) and these medications has been associated with an increased risk of bleeding. Advise them 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 ( 5.3 )] . 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 ( 5.4 )] . Discontinuation Syndrome Advise patients not to abruptly discontinue vilazodone hydrochloride tablets and to discuss any tapering regimen with their healthcare provider. Adverse reactions can occur when vilazodone hydrochloride tablets are discontinued [see Warnings and Precautions ( 5.5 )] . Seizures Caution patients about using vilazodone hydrochloride tablets if they have a history of a seizure disorder [see Warnings and Precautions ( 5.6 )] . Sexual Dysfunction Advise patients that use of vilazodone hydrochloride 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 ( 5.9 )] . 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 ( 6.2 )] . Concomitant Medications Advise patients to inform their health care providers if they are taking, or plan to take any prescription or over-the-counter medications since there is a potential for interactions [see Drug Interactions ( 7.1 )] .

ash, hives, swelling, or difficulty breathing [see Adverse Reactions ( 6.2 )] . Concomitant Medications Advise patients to inform their health care providers if they are taking, or plan to take any prescription or over-the-counter medications since there is a potential for interactions [see Drug Interactions ( 7.1 )] . Pregnancy Advise pregnant women to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with vilazodone hydrochloride tablets [see Use in Specific Populations ( 8.1 )] . Advise patients that vilazodone hydrochloride tablets use late 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 Use in Specific Populations ( 8.1 )] . Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to vilazodone hydrochloride tablets during pregnancy [see Use in Specific Populations ( 8.1 )] . Dispense with Medication Guide available at: www.tevausa.com/medguides Manufactured In Croatia By: Pliva Hrvatska d.o.o. Zagreb, Croatia Manufactured For: Teva Pharmaceuticals Parsippany, NJ 07054 Rev. B 4/2024 Marketed by: GSMS, Inc. Camarillo, CA 93012 USA

Dispense with Medication Guide available at: www.tevausa.com/medguides MEDICATION GUIDE Vilazodone Hydrochloride ( vil az′ oh done hye″ droe klor′ ide) Tablets, for oral use What is the most important information I should know about vilazodone hydrochloride tablets? Vilazodone hydrochloride tablets may cause serious side effects, including: Increased risk of suicidal thoughts or actions in some children, adolescents, and young adults. Vilazodone hydrochloride tablets and other antidepressant medicines may increase suicidal thoughts or actions in some people 24 years of age and younger, especially within the first few months of treatment or when the dose is changed. Vilazodone hydrochloride tablets are not for use in children. Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions. Some people may have a higher risk of having suicidal thoughts or actions. These include people who have (or have a family history of) depression, bipolar illness (also called manic-depressive illness) or have a history of suicidal thoughts or 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 dose is changed. Call your healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings. 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 or your family member have any of the following symptoms, especially if they are new, worse, or worry you: attempts to commit suicide acting aggressive, being angry or violent new or worse depression panic attacks new or worse irritability an extreme increase in activity or talking (mania) acting on dangerous impulses thoughts about suicide or dying new or worse anxiety feeling agitated or restless trouble sleeping (insomnia) other unusual changes in behavior or mood What is vilazodone hydrochloride tablets? Vilazodone hydrochloride tablets are a prescription medicine used to treat a certain type of depression called Major Depressive Disorder (MDD) in adults. It is not known if vilazodone hydrochloride tablets are safe and effective for use in children for the treatment of MDD. Who should not take vilazodone hydrochloride tablets? Do not take vilazodone hydrochloride 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 Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid or intravenous methylene blue. Do not start taking an MAOI for at least 14 days after you stop treatment with vilazodone hydrochloride tablets.

th the antibiotic linezolid or intravenous methylene blue Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid or intravenous methylene blue. Do not start taking an MAOI for at least 14 days after you stop treatment with vilazodone hydrochloride tablets. Before taking vilazodone hydrochloride tablets, tell your healthcare provider about all your medical conditions, including if you: have or have a family history of suicide, depression, bipolar disorder, mania or hypomania have or had bleeding problems have or had seizures or convulsions have high pressure in the eye (glaucoma) have or had seizures or convulsions have low sodium levels in your blood drink alcohol are pregnant or plan to become pregnant. Taking vilazodone hydrochloride tablets late in pregnancy may lead to an increased risk of certain problems in your newborn. Talk to your healthcare provider about the risks to your baby if you take vilazodone hydrochloride tablets during pregnancy. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with vilazodone hydrochloride tablets. There is a pregnancy registry for females who are exposed to vilazodone hydrochloride tablets pregnancy. The purpose of the registry is to collect information about the health of females exposed to vilazodone hydrochloride tablets and their baby. If you become pregnant during treatment with vilazodone hydrochloride tablets, talk to your healthcare provider about registering with the National Pregnancy Registry for Antidepressants. You can register by calling 1-844-405-6185 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/antidepressants . are breastfeeding or plan to breastfeed. It is not known if vilazodone hydrochloride passes into breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with vilazodone hydrochloride tablets. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Vilazodone hydrochloride tablets and some medicines may affect each other causing possible serious side effects. Vilazodone hydrochloride tablets may affect the way other medicines work and other medicines may affect the way vilazodone hydrochloride tablets work. Especially tell your healthcare provider if you take: MAOIs medicines used to treat migraine headaches known as 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) and warfarin diuretics medicines used to treat mood, anxiety, psychotic or thought disorders, including selective serotonin reuptake inhibitors (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 vilazodone hydrochloride tablets with your other medicines. Do not start or stop any other medicines during treatment with vilazodone hydrochloride tablets without talking to your healthcare provider first. Stopping vilazodone hydrochloride tablets suddenly may cause you to have serious side effects. See, “What are the possible side effects of vilazodone hydrochloride 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 vilazodone hydrochloride tablets? Take vilazodone hydrochloride tablets exactly as your healthcare provider tell you to.

e side effects of vilazodone hydrochloride 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 vilazodone hydrochloride tablets? Take vilazodone hydrochloride tablets exactly as your healthcare provider tell you to. Do not change your dose or stop taking vilazodone hydrochloride tablets without first talking to your healthcare provider. Your healthcare provider may need to change the dose of vilazodone hydrochloride tablets until it is the right dose for you. Take vilazodone hydrochloride tablets 1 time each day with food. If you miss a dose of vilazodone hydrochloride tablets, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of vilazodone hydrochloride tablets at the same time. If you take too many vilazodone hydrochloride tablets, call your healthcare provider or poison control center at 1-800-222-1222 right away, or get emergency treatment right away. What should I avoid while taking vilazodone hydrochloride tablet? Do not drive, operate heavy machinery, or do other dangerous activities until you know how vilazodone hydrochloride tablets affect you. Vilazodone hydrochloride tablets can cause sleepiness or may affect your ability to make decisions, think clearly, or react quickly. Avoid drinking alcohol during treatment with vilazodone hydrochloride tablets. What are the possible side effects of vilazodone hydrochloride tablets? Vilazodone hydrochloride tablets may cause serious side effects, including: See , “What is the most important information I should know about vilazodone hydrochloride tablets?” Serotonin Syndrome. A potentially life-threatening problem called serotonin syndrome can happen when vilazodone hydrochloride tablets are taken with certain other medicines. See, “Who should not take vilazodone hydrochloride tablets?” Stop taking vilazodone hydrochloride tablets and 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 confusion fast heart beat dizziness flushing tremors, stiff muscles, or muscle twitching seizures seeing or hearing things that are not real (hallucinations) coma blood pressure changes sweating high body temperature (hyperthermia) loss of coordination nausea, vomiting, diarrhea Increased risk of bleeding. Taking vilazodone hydrochloride tablets with aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), warfarin or blood thinners may add to this risk. Tell your healthcare provider right away about any unusual bleeding or bruising. Mania or hypomania (manic episodes) in people who have a history of bipolar disorder. Symptoms may include: greatly increased energy racing thoughts unusually grand ideas talking more or faster than usual severe trouble sleeping reckless behavior excessive happiness or irritability Discontinuation syndrome. Suddenly stopping vilazodone hydrochloride tablets may cause you to have serious side effects. Your healthcare provider may want to decrease your dose slowly. Symptoms may include: nausea changes in your mood irritability and agitation dizziness electric shock sensation (paresthesia) anxiety confusion sweating headache tiredness problems sleeping hypomania ringing in your ears (tinnitus) seizures Seizures (convulsions). Eye problems (angle-closure glaucoma): Vilazodone hydrochloride tablets may cause a certain type of eye problem called angle-closure glaucoma. Call your healthcare provider if you have changes in your vision or eye pain. Low sodium levels in your blood (hyponatremia).

ur ears (tinnitus) seizures Seizures (convulsions). Eye problems (angle-closure glaucoma): Vilazodone hydrochloride tablets may cause a certain type of eye problem called angle-closure glaucoma. Call your healthcare provider if you have changes in your vision or eye pain. Low sodium levels in your blood (hyponatremia). Low sodium levels in your blood may be serious and may cause death. Elderly people may be at greater risk for this. Signs and Symptoms of low sodium levels in your blood may include: headache memory changes weakness and unsteadiness on your feet which can lead to falls difficulty concentrating confusion In severe or more sudden cases, signs and symptoms include: hallucinations (seeing or hearing things that are not real) seizures respiratory arrest fainting coma death Sexual problems (dysfunction). Taking selective serotonin reuptake inhibitors (SSRIs), including vilazodone hydrochloride tablets, may cause sexual problems. Symptoms in males may include: delayed ejaculation or inability to have an ejaculation problems getting or keeping an erection decreased sex drive Symptoms in females may include: decreased sex drive 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 vilazodone hydrochloride tablets. There may be treatments your healthcare provider can suggest. The most common side effects of vilazodone hydrochloride tablets include diarrhea, nausea or vomiting, trouble sleeping. These are not all the possible side effects of vilazodone hydrochloride 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 vilazodone hydrochloride tablets? Store vilazodone hydrochloride tablets at room temperature between 68°F to 77°F (20°C to 25°C). Keep vilazodone hydrochloride tablets and all medicines out of the reach of children. General information about the safe and effective use of vilazodone hydrochloride tablets. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use vilazodone hydrochloride tablets for a condition for which it was not prescribed. Do not give vilazodone hydrochloride 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 vilazodone hydrochloride tablets that is written for healthcare professionals. What are the ingredients in vilazodone hydrochloride tablets? Active ingredient: vilazodone hydrochloride Inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol 3350, polyvinyl alcohol – part hydrolyzed, talc and titanium dioxide. Additionally, the 10 mg tablets contain iron oxide red, the 20 mg tablets contain iron oxide red and iron oxide yellow, and the 40 mg tablets contain FD&C Blue #2/indigo carmine aluminum lake. Manufactured In Croatia By: Pliva Hrvatska d.o.o., Zagreb, Croatia Manufactured For: Teva Pharmaceuticals, Parsippany, NJ 07054 For more information about vilazodone hydrochloride tablets call Teva at 1-888-838-2872. Marketed by: GSMS, Inc. Camarillo, CA 93012 USA This Medication Guide has been approved by the U.S. Food and Drug Administration. Rev. B 4/2024

<table cellpadding="5"><colgroup><col/><col/></colgroup><tbody><tr><td colspan="2"><paragraph>Dispense with Medication Guide available at: www.tevausa.com/medguides</paragraph></td></tr><tr><td align="center" colspan="2" styleCode="Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold"><content styleCode="bold">MEDICATION GUIDE</content></content></paragraph><paragraph><content styleCode="bold">Vilazodone Hydrochloride (</content><content styleCode="bold">vil az&#x2032; oh done hye&#x2033; droe klor&#x2032; ide) Tablets, for oral use </content></paragraph></td></tr><tr><td colspan="2" styleCode="Toprule Lrule Rrule"><paragraph><content styleCode="bold">What is the most important information I should know about vilazodone hydrochloride tablets?</content></paragraph><paragraph><content styleCode="bold">Vilazodone hydrochloride tablets may cause serious side effects, including:</content></paragraph><list listType="unordered"><item><content styleCode="bold">Increased risk of suicidal thoughts or actions in some children, adolescents, and young adults.</content>Vilazodone hydrochloride tablets and other antidepressant medicines may increase suicidal thoughts or actions in some people 24 years of age and younger, <content styleCode="bold">especially within the first few months of treatment or when the dose is changed.</content><content styleCode="bold">Vilazodone hydrochloride tablets are not for use in children.</content><list listType="unordered" styleCode="Circle"><item><content styleCode="bold">Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions. Some people may have a higher risk of having suicidal thoughts or actions. </content>These include people who have (or have a family history of) depression, bipolar illness (also called manic-depressive illness) or have a history of suicidal thoughts or actions. </item></list></item></list><paragraph><content styleCode="bold"><content styleCode="bold">How can I watch for and try to prevent suicidal thoughts and actions?</content></content></paragraph><list listType="unordered" styleCode="Circle"><item>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.</item><item>Call your healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings.</item><item>Keep all follow-up visits with your healthcare provider as scheduled.

ghts or actions. This is very important when an antidepressant medicine is started or when the dose is changed.</item><item>Call your healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings.</item><item>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.</item></list><content styleCode="bold">Call your healthcare provider or get emergency medical help right away if you or your family member have any of the following symptoms, especially if they are new, worse, or worry you: </content></td></tr><tr><td styleCode="Botrule Lrule"><list listType="unordered"><item>attempts to commit suicide</item><item>acting aggressive, being angry or violent</item><item>new or worse depression</item><item>panic attacks</item><item>new or worse irritability</item><item>an extreme increase in activity or talking (mania)</item></list></td><td styleCode="Botrule Rrule"><list listType="unordered"><item>acting on dangerous impulses</item><item>thoughts about suicide or dying</item><item>new or worse anxiety</item><item>feeling agitated or restless</item><item>trouble sleeping (insomnia)</item><item>other unusual changes in behavior or mood</item></list></td></tr><tr><td colspan="2" styleCode="Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">What is</content><content styleCode="bold">vilazodone hydrochloride tablets?</content></paragraph><paragraph>Vilazodone hydrochloride tablets are a prescription medicine used to treat a certain type of depression called Major Depressive Disorder (MDD) in adults.</paragraph> It is not known if vilazodone hydrochloride tablets are safe and effective for use in children for the treatment of MDD. </td></tr><tr><td colspan="2" styleCode="Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">Who should not take</content><content styleCode="bold">vilazodone hydrochloride tablets?</content></paragraph><paragraph><content styleCode="bold">Do not take</content><content styleCode="bold">vilazodone hydrochloride tablets if you:</content></paragraph><list listType="unordered"><item>take a Monoamine Oxidase Inhibitor (MAOI)</item><item>have stopped taking an MAOI in the last 14 days</item><item>are being treated with the antibiotic linezolid or intravenous methylene blue</item></list><paragraph>Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid or intravenous methylene blue.</paragraph><content styleCode="bold">Do not start taking an MAOI for at least 14 days after you stop treatment with vilazodone hydrochloride tablets.</content></td></tr><tr><td colspan="2" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Before taking </content><content styleCode="bold">vilazodone hydrochloride tablets, tell your healthcare provider about all your medical conditions, including if you:</content><list listType="unordered"><item>have or have a family history of suicide, depression, bipolar disorder, mania or hypomania</item><item>have or had bleeding problems</item><item>have or had seizures or convulsions</item><item>have high pressure in the eye (glaucoma)</item><item>have or had seizures or convulsions</item><item>have low sodium levels in your blood</item><item>drink alcohol</item><item>are pregnant or plan to become pregnant. Taking vilazodone hydrochloride tablets late in pregnancy may lead to an increased risk of certain problems in your newborn. Talk to your healthcare provider about the risks to your baby if you take vilazodone hydrochloride tablets during pregnancy.

tem>drink alcohol</item><item>are pregnant or plan to become pregnant. Taking vilazodone hydrochloride tablets late in pregnancy may lead to an increased risk of certain problems in your newborn. Talk to your healthcare provider about the risks to your baby if you take vilazodone hydrochloride tablets during pregnancy. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with vilazodone hydrochloride tablets. <list listType="unordered" styleCode="Circle"><item>There is a pregnancy registry for females who are exposed to vilazodone hydrochloride tablets pregnancy. The purpose of the registry is to collect information about the health of females exposed to vilazodone hydrochloride tablets and their baby. If you become pregnant during treatment with vilazodone hydrochloride tablets, talk to your healthcare provider about registering with the National Pregnancy Registry for Antidepressants. You can register by calling 1-844-405-6185 or visiting online at <content styleCode="italics">https://womensmentalhealth.org/research/pregnancyregistry/antidepressants</content>. </item></list></item><item>are breastfeeding or plan to breastfeed. It is not known if vilazodone hydrochloride passes into breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with vilazodone hydrochloride tablets.</item></list><paragraph><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. </paragraph><paragraph>Vilazodone hydrochloride tablets and some medicines may affect each other causing possible serious side effects. Vilazodone hydrochloride tablets may affect the way other medicines work and other medicines may affect the way vilazodone hydrochloride tablets work.</paragraph><paragraph><content styleCode="bold">Especially tell your healthcare provider if you take:</content></paragraph><list listType="unordered"><item>MAOIs</item><item>medicines used to treat migraine headaches known as 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&#x2019;s Wort</item><item>medicines that can affect blood clotting such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) and warfarin</item><item>diuretics</item><item>medicines used to treat mood, anxiety, psychotic or thought disorders, including selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs)</item></list><paragraph>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 vilazodone hydrochloride tablets with your other medicines. Do not start or stop any other medicines during treatment with vilazodone hydrochloride tablets without talking to your healthcare provider first. Stopping vilazodone hydrochloride tablets suddenly may cause you to have serious side effects. See, <content styleCode="bold">&#x201C;What are the possible side effects of vilazodone hydrochloride 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. </paragraph></td></tr><tr><td colspan="2" styleCode="Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">How should I take vilazodone hydrochloride tablets?</content></paragraph><list listType="unordered"><item>Take vilazodone hydrochloride tablets exactly as your healthcare provider tell you to.

edicine. </paragraph></td></tr><tr><td colspan="2" styleCode="Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">How should I take vilazodone hydrochloride tablets?</content></paragraph><list listType="unordered"><item>Take vilazodone hydrochloride tablets exactly as your healthcare provider tell you to. Do not change your dose or stop taking vilazodone hydrochloride tablets without first talking to your healthcare provider.</item><item>Your healthcare provider may need to change the dose of vilazodone hydrochloride tablets until it is the right dose for you.</item><item><content styleCode="bold">Take vilazodone hydrochloride tablets 1 time each day with food.</content></item><item>If you miss a dose of vilazodone hydrochloride tablets, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of vilazodone hydrochloride tablets at the same time.</item><item>If you take too many vilazodone hydrochloride tablets, call your healthcare provider or poison control center at 1-800-222-1222 right away, or get emergency treatment right away. </item></list></td></tr><tr><td colspan="2" styleCode="Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">What should I avoid while taking</content><content styleCode="bold">vilazodone hydrochloride tablet?</content></paragraph><list listType="unordered"><item>Do not drive, operate heavy machinery, or do other dangerous activities until you know how vilazodone hydrochloride tablets affect you. Vilazodone hydrochloride tablets can cause sleepiness or may affect your ability to make decisions, think clearly, or react quickly.</item><item>Avoid drinking alcohol during treatment with vilazodone hydrochloride tablets. </item></list></td></tr><tr><td colspan="2" styleCode="Toprule Lrule Rrule"><paragraph><content styleCode="bold">What are the possible side effects of vilazodone hydrochloride tablets?</content></paragraph><paragraph><content styleCode="bold">Vilazodone hydrochloride tablets may cause serious side effects, including:</content></paragraph><list listType="unordered"><item>See <content styleCode="bold">, &#x201C;What is the most important information I should know about vilazodone hydrochloride tablets?&#x201D;</content></item><item><content styleCode="bold">Serotonin Syndrome.</content>A potentially life-threatening problem called serotonin syndrome can happen when vilazodone hydrochloride tablets are taken with certain other medicines.

most important information I should know about vilazodone hydrochloride tablets?&#x201D;</content></item><item><content styleCode="bold">Serotonin Syndrome.</content>A potentially life-threatening problem called serotonin syndrome can happen when vilazodone hydrochloride tablets are taken with certain other medicines. See, <content styleCode="bold">&#x201C;Who should not take</content><content styleCode="bold">vilazodone hydrochloride tablets?&#x201D;</content>Stop taking vilazodone hydrochloride tablets and 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: </item></list></td></tr><tr><td styleCode="Lrule"><list listType="unordered" styleCode="Circle"><item>agitation</item><item>confusion</item><item>fast heart beat</item><item>dizziness</item><item>flushing</item><item>tremors, stiff muscles, or muscle twitching</item><item>seizures</item></list></td><td styleCode="Rrule"><list listType="unordered" styleCode="Circle"><item>seeing or hearing things that are not real (hallucinations)</item><item>coma</item><item>blood pressure changes</item><item>sweating</item><item>high body temperature (hyperthermia)</item><item>loss of coordination</item><item>nausea, vomiting, diarrhea</item></list></td></tr><tr><td colspan="2" styleCode="Lrule Rrule"><list listType="unordered"><item><content styleCode="bold">Increased risk of bleeding.</content>Taking vilazodone hydrochloride tablets with aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), warfarin or blood thinners may add to this risk. Tell your healthcare provider right away about any unusual bleeding or bruising. </item><item><content styleCode="bold">Mania or hypomania (manic episodes)</content>in people who have a history of bipolar disorder. Symptoms may include: </item></list></td></tr><tr><td styleCode="Lrule"><list listType="unordered" styleCode="Circle"><item>greatly increased energy</item><item>racing thoughts</item><item>unusually grand ideas</item><item>talking more or faster than usual</item></list></td><td styleCode="Rrule"><list listType="unordered" styleCode="Circle"><item>severe trouble sleeping</item><item>reckless behavior</item><item>excessive happiness or irritability</item></list></td></tr><tr><td colspan="2" styleCode="Lrule Rrule"><list listType="unordered"><item><content styleCode="bold">Discontinuation syndrome.</content>Suddenly stopping vilazodone hydrochloride tablets may cause you to have serious side effects. Your healthcare provider may want to decrease your dose slowly. Symptoms may include: </item></list></td></tr><tr><td styleCode="Lrule"><list listType="unordered" styleCode="Circle"><item>nausea</item><item>changes in your mood</item><item>irritability and agitation</item><item>dizziness</item><item>electric shock sensation (paresthesia)</item><item>anxiety</item><item>confusion</item></list></td><td styleCode="Rrule"><list listType="unordered" styleCode="Circle"><item>sweating</item><item>headache</item><item>tiredness</item><item>problems sleeping</item><item>hypomania</item><item>ringing in your ears (tinnitus)</item><item>seizures </item></list></td></tr><tr><td colspan="2" styleCode="Lrule Rrule"><list listType="unordered"><item><content styleCode="bold">Seizures (convulsions).</content></item><item><content styleCode="bold">Eye problems (angle-closure glaucoma):</content>Vilazodone hydrochloride tablets may cause a certain type of eye problem called angle-closure glaucoma. Call your healthcare provider if you have changes in your vision or eye pain. </item><item><content styleCode="bold">Low sodium levels in your blood (hyponatremia).</content>Low sodium levels in your blood may be serious and may cause death.

tablets may cause a certain type of eye problem called angle-closure glaucoma. Call your healthcare provider if you have changes in your vision or eye pain. </item><item><content styleCode="bold">Low sodium levels in your blood (hyponatremia).</content>Low sodium levels in your blood may be serious and may cause death. Elderly people may be at greater risk for this. Signs and Symptoms of low sodium levels in your blood may include: </item></list></td></tr><tr><td styleCode="Lrule"><list listType="unordered" styleCode="Circle"><item>headache</item><item>memory changes</item><item>weakness and unsteadiness on your feet which can lead to falls </item></list></td><td styleCode="Rrule"><list listType="unordered" styleCode="Circle"><item>difficulty concentrating</item><item>confusion</item></list></td></tr><tr><td colspan="2" styleCode="Lrule Rrule"><paragraph><content styleCode="bold">In severe or more sudden cases, signs and symptoms include: </content></paragraph></td></tr><tr><td styleCode="Lrule"><list listType="unordered" styleCode="Circle"><item>hallucinations (seeing or hearing things that are not real)</item><item>seizures</item><item>respiratory arrest </item></list></td><td styleCode="Rrule"><list listType="unordered" styleCode="Circle"><item>fainting</item><item>coma</item><item>death</item></list></td></tr><tr><td colspan="2" styleCode="Lrule Rrule"><list listType="unordered"><item><content styleCode="bold">Sexual problems (dysfunction).</content>Taking selective serotonin reuptake inhibitors (SSRIs), including vilazodone hydrochloride tablets, may cause sexual problems. </item></list><paragraph> Symptoms in males may include:</paragraph></td></tr><tr><td styleCode="Lrule"><list listType="unordered" styleCode="Circle"><item>delayed ejaculation or inability to have an ejaculation</item><item>problems getting or keeping an erection</item></list></td><td styleCode="Rrule"><list listType="unordered" styleCode="Circle"><item> decreased sex drive</item></list></td></tr><tr><td colspan="2" styleCode="Lrule Rrule"> Symptoms in females may include:</td></tr><tr><td styleCode="Lrule"><list listType="unordered" styleCode="Circle"><item> decreased sex drive</item></list></td><td styleCode="Rrule"><list listType="unordered" styleCode="Circle"><item>delayed orgasm or inability to have an orgasm</item></list></td></tr><tr><td colspan="2" styleCode="Botrule Lrule Rrule">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 vilazodone hydrochloride tablets. There may be treatments your healthcare provider can suggest. <paragraph><content styleCode="bold">The most common side effects of </content><content styleCode="bold">vilazodone hydrochloride tablets include </content>diarrhea, nausea or vomiting, trouble sleeping. </paragraph><paragraph>These are not all the possible side effects of vilazodone hydrochloride tablets.</paragraph> 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 colspan="2" styleCode="Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">How should I store vilazodone hydrochloride tablets?</content></paragraph><list listType="unordered"><item>Store vilazodone hydrochloride tablets at room temperature between 68&#xB0;F to 77&#xB0;F (20&#xB0;C to 25&#xB0;C).</item><item><content styleCode="bold">Keep</content><content styleCode="bold">vilazodone hydrochloride tablets and all medicines out of the reach of children.

></paragraph><list listType="unordered"><item>Store vilazodone hydrochloride tablets at room temperature between 68&#xB0;F to 77&#xB0;F (20&#xB0;C to 25&#xB0;C).</item><item><content styleCode="bold">Keep</content><content styleCode="bold">vilazodone hydrochloride tablets and all medicines out of the reach of children. </content></item></list></td></tr><tr><td colspan="2" styleCode="Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">General information about the safe and effective use of vilazodone hydrochloride tablets.</content></paragraph> Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use vilazodone hydrochloride tablets for a condition for which it was not prescribed. Do not give vilazodone hydrochloride 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 vilazodone hydrochloride tablets that is written for healthcare professionals. </td></tr><tr><td colspan="2" styleCode="Botrule Toprule Lrule Rrule"><paragraph><content styleCode="bold">What are the ingredients in vilazodone hydrochloride tablets?</content></paragraph><paragraph><content styleCode="bold">Active ingredient:</content>vilazodone hydrochloride </paragraph><paragraph><content styleCode="bold">Inactive ingredients:</content>colloidal silicon dioxide, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol 3350, polyvinyl alcohol &#x2013; part hydrolyzed, talc and titanium dioxide. Additionally, the 10 mg tablets contain iron oxide red, the 20 mg tablets contain iron oxide red and iron oxide yellow, and the 40 mg tablets contain FD&amp;C Blue #2/indigo carmine aluminum lake. </paragraph><paragraph>Manufactured In Croatia By: <content styleCode="bold">Pliva Hrvatska d.o.o.,</content>Zagreb, Croatia Manufactured For: <content styleCode="bold">Teva Pharmaceuticals,</content>Parsippany, NJ 07054 </paragraph><paragraph>For more information about vilazodone hydrochloride tablets call Teva at 1-888-838-2872.</paragraph><paragraph>Marketed by:</paragraph><paragraph><content styleCode="bold">GSMS, Inc.</content></paragraph><paragraph>Camarillo, CA 93012 USA</paragraph></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 [ . Vilazodone hydrochloride tablets is not approved for use in pediatric patients [see ] . • Antidepressants increase the risk of suicidal thoughts and behaviors in pediatric and young adult patients () • Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors () • Vilazodone hydrochloride tablets is not approved for use in pediatric patients ()

1 INDICATIONS AND USAGE Vilazodone hydrochloride tablets are indicated for the treatment of major depressive disorder (MDD) in adults ]. Vilazodone hydrochloride tablets are indicated for the treatment of major depressive disorder (MDD) in adults ().

2 DOSAGE AND ADMINISTRATION • Recommended target dosage: 20 mg to 40 mg once daily with food ( 2.1 , ). • To titrate: start with initial dosage of 10 mg once daily for 7 days, followed by 20 mg once daily. The dose may be increased up to 40 mg once daily after a minimum of 7 days between dosage increases ( 2.1 ). • Prior to initiating vilazodone hydrochloride, screen for bipolar disorder (, ). • When discontinuing vilazodone hydrochloride, reduce dosage gradually (, ). 2.1 Dosage for Treatment of Major Depressive Disorder The recommended target dosage for vilazodone hydrochloride is 20 mg to 40 mg orally once daily with food [see Clinical Pharmacology (12.3), . To achieve the target dosage, titrate vilazodone hydrochloride as follows: • Start with an initial dosage of 10 mg once daily with food for 7 days, • Then increase to 20 mg once daily with food. • The dose may be increased up to 40 mg once daily with food after a minimum of 7 days between dosage increases. If a dose is missed, it should be taken as soon as the patient remembers. If it is almost time for the next dose, the patient should skip the missed dose and take the next dose at the regular time. Two doses should not be taken at the same time. 2.2 Screen for Bipolar Disorder Prior to Starting Vilazodone Hydrochloride Prior to initiating treatment with vilazodone hydrochloride tablets or another antidepressant, screen patients for a personal or family history of bipolar disorder, mania, or hypomania 2.3 Switching to or from a Monoamine Oxidase Inhibitor Antidepressant At least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI) antidepressant and initiation of vilazodone hydrochloride. In addition, at least 14 days must elapse after stopping vilazodone hydrochloride before starting an MAOI antidepressant [ see Contraindications (4) , ]. 2.4 Dosage Adjustments with CYP3A4 Inhibitors or Inducers Patients receiving concomitant CYP3A4 inhibitors: During concomitant use of a strong CYP3A4 inhibitor (e.g., itraconazole, clarithromycin, voriconazole), the vilazodone hydrochloride dose should not exceed 20 mg once daily. The original vilazodone hydrochloride dose level, can be resumed when the CYP3A4 inhibitor is discontinued [ see Drug Interactions (7) ]. Patients receiving concomitant CYP3A4 inducers: Based on clinical response, consider increasing the dosage of vilazodone hydrochloride by 2-fold, up to a maximum 80 mg once daily, over 1 to 2 weeks in patients taking strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin) for greater than 14 days. If CYP3A4 inducers are discontinued, gradually reduce the vilazodone hydrochloride dosage to its original level over 1 to 2 weeks [ see Drug Interactions (7) ]. 2.5 Discontinuing Treatment with Vilazodone Hydrochloride Adverse reactions may occur upon discontinuation of vilazodone hydrochloride [ ] . A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible. Vilazodone hydrochloride should be down tapered from the 40 mg once daily dose to 20 mg once daily for 4 days, followed by 10 mg once daily for 3 days. Patients taking vilazodone hydrochloride 20 mg once daily should be tapered to 10 mg once daily for 7 days.

3 DOSAGE FORMS AND STRENGTHS Vilazodone Hydrochloride Tablets are available as 10 mg, 20 mg and 40 mg film-coated tablets. 10 mg: Pink colored, ellipse shaped, biconvex, film coated tablets, debossed with “MV” on one side and “14” on other side, free from physical defects. 20 mg: Orange colored, ellipse shaped, biconvex, film coated tablets, debossed with “MV” on one side and “15” on other side, free from physical defects. 40 mg: Blue colored, ellipse shaped, biconvex, film coated tablets, debossed with “MV” on one side and “16” on other side, free from physical defects Tablets: 10 mg, 20 mg and 40 mg ()

4 CONTRAINDICATIONS Vilazodone hydrochloride tablets are contraindicated in: • Patients taking, or within 14 days of stopping, monoamine oxidase inhibitors (MAOIs), including MAOIs such as linezolid or intravenous methylene blue, because of an increased risk of serotonin syndrome [ ), Drug Interactions (7) ]. • Concomitant use of monoamine oxidase inhibitors (MAOIs), or use within 14 days of stopping MAOIs ( 4 ).

5 WARNINGS AND PRECAUTIONS • Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents (e.g., SSRI, SNRI, triptans, amphetamines), but also when taken alone. If it occurs, discontinue vilazodone hydrochloride and initiate supportive treatment (). • Increased Risk of Bleeding: Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), other antiplatelet drugs, warfarin, and other anticoagulants may increase this risk (). • Activation of Mania/Hypomania: Screen patients for bipolar disorder (). • Seizures: Can occur with treatment. Use with caution in patients with a seizure disorder (). • Angle Closure Glaucoma: Avoid use of antidepressants, including vilazodone hydrochloride, in patients with untreated anatomically narrow angles. (). • Sexual Dysfunction: Vilazodone hydrochloride may cause symptoms of sexual dysfunction (). 5.1 Suicidal Thoughts and Behavior 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 over 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater in antidepressant-treated patients 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 1. Table 1: Risk Differences of the Number of Patients with Suicidal Thoughts or Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients Age Range (years) Drug-Placebo Difference in Number of Patients with Suicidal Thoughts or Behaviors per 1000 Patients Treated Increases Compared to Placebo <18 14 additional patients 18-24 5 additional patients Decreases Compared to Placebo 25-64 1 fewer patient ≥65 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 studies 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 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 vilazodone hydrochloride, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors. 5.2 Serotonin Syndrome Serotonin and norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitor (SSRIs), including vilazodone hydrochloride, can precipitate serotonin syndrome, a potentially life-threatening condition.

ly worse, or who are experiencing emergent suicidal thoughts or behaviors. 5.2 Serotonin Syndrome Serotonin and norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitor (SSRIs), including vilazodone hydrochloride, 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, tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [ see Contraindications (4) and Drug Interactions (7) ] . Serotonin syndrome can also occur when these drugs are used alone. Symptoms of serotonin syndrome were noted in 0.1% of MDD patients treated with vilazodone hydrochloride in premarketing clinical trials. 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 vilazodone hydrochloride with MAOIs is contraindicated. In addition, do not initiate vilazodone hydrochloride 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 vilazodone hydrochloride, discontinue vilazodone hydrochloride before initiating treatment with the MAOI [ see Contraindications (4) , )]. Monitor all patients taking vilazodone hydrochloride for the emergence of serotonin syndrome. Discontinue treatment with vilazodone hydrochloride and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of vilazodone hydrochloride with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms. 5.3 Increased Risk of Bleeding Drugs that interfere with serotonin reuptake inhibition, including vilazodone hydrochloride, 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. Bleeding events related to drugs that interfere with serotonin reuptake 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 vilazodone hydrochloride and antiplatelet agents or anticoagulants. For patients taking warfarin, carefully monitor coagulation indices when initiating, titrating, or discontinuing vilazodone hydrochloride. 5.4 Activation of Mania or Hypomania In patients with bipolar disorder, treating a depressive episode with vilazodone hydrochloride or another antidepressant may precipitate a mixed/manic episode. In controlled clinical trials, patients with bipolar disorder were excluded; however, symptoms of mania or hypomania were reported in 0.1% of undiagnosed patients treated with vilazodone hydrochloride.

ng a depressive episode with vilazodone hydrochloride or another antidepressant may precipitate a mixed/manic episode. In controlled clinical trials, patients with bipolar disorder were excluded; however, symptoms of mania or hypomania were reported in 0.1% of undiagnosed patients treated with vilazodone hydrochloride. Prior to initiating treatment with vilazodone hydrochloride, screen patients for any personal or family history of bipolar disorder, mania, or hypomania [ ]. 5.5 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 [ ]. 5.6 Seizures Vilazodone hydrochloride has not been systematically evaluated in patients with a seizure disorder. Patients with a history of seizures were excluded from clinical studies. Vilazodone hydrochloride should be prescribed with caution in patients with a seizure disorder. 5.7 Angle-Closure Glaucoma The pupillary dilation that occurs following use of many antidepressant drugs including vilazodone hydrochloride may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy. Avoid use of antidepressants, including vilazodone hydrochloride, in patients with untreated anatomically narrow angles. 5.8 Hyponatremia Hyponatremia may occur as a result of treatment with SNRIs and SSRIs, including vilazodone hydrochloride. Cases of 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 vilazodone hydrochloride 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 and SNRIs [ )] . 5.9 Sexual Dysfunction Use of SSRIs, including vilazodone hydrochloride, may cause symptoms of sexual dysfunction [ ] . 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 vilazodone hydrochloride 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 cellpadding="0pt" cellspacing="0pt" width="100%"><col width="12%"/><col width="88%"/><tbody><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph> <content styleCode="bold">Age Range</content> <content styleCode="bold">(years)</content> </paragraph></td><td align="center" styleCode="Rrule Botrule Toprule " valign="top"><paragraph> <content styleCode="bold">Drug-Placebo Difference in Number of Patients with Suicidal Thoughts or Behaviors per 1000</content> <content styleCode="bold">Patients Treated</content> </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph> <content styleCode="bold">Increases Compared to Placebo</content> </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> &lt;18 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph> 14 additional patients </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> 18-24 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph> 5 additional patients </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph> <content styleCode="bold">Decreases Compared to Placebo</content> </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> 25-64 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph> 1 fewer patient </paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="top"><paragraph> &#x2265;65 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph> 6 fewer patients </paragraph></td></tr></tbody></table>

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: • Suicidal Thoughts and Behaviors in Adolescents and Young Adults [ ]. • Serotonin Syndrome [ ]. • Increased Risk of Bleeding [ ]. • Activation of Mania or Hypomania [ ]. • Discontinuation Syndrome [ ]. • Seizures [ ]. • Angle-Closure Glaucoma [ ]. • Hyponatremia [ ]. • Sexual Dysfunction [ ]. Most common adverse reactions (incidence ≥ 5% and at least twice the rate of placebo): diarrhea, nausea, vomiting, and insomnia ( 6 ).To report SUSPECTED ADVERSE REACTIONS, contact Novadoz Pharmaceuticals LLC at 1-855-668-2369 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 and varying lengths of time, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect rates observed in practice. The most commonly observed adverse reactions in vilazodone hydrochloride-treated patients with major depressive disorder (MDD) in placebo-controlled studies (incidence ≥ 5% and at least twice the rate of placebo) were diarrhea, nausea, vomiting, and insomnia. Patient Exposure The safety of vilazodone hydrochloride was evaluated in 3,007 patients (18 to 70 years of age) diagnosed with MDD who participated in clinical studies, representing 676 patient-years of exposure. In an open-label 52 week study at 40 mg daily, 599 patients were exposed to vilazodone hydrochloride for a total of 348 patient-years. The adverse reaction information presented below was derived from studies of vilazodone hydrochloride 20 mg and 40 mg daily in patients with MDD including: • Four placebo-controlled 8 to 10-week studies in 2,233 patients, including 1,266 vilazodone hydrochloride-treated patients; and • An open-label 52-week study of 599 vilazodone hydrochloride-treated patients. These studies included a titration period of 10 mg daily for 7 days, followed by 20 mg daily for 7 days or to 40 mg daily over 2 weeks. In these clinical trials, vilazodone hydrochloride was administered with food. Adverse reactions reported as reasons for discontinuation of treatment In these studies, 7.3% of the vilazodone hydrochloride-treated patients discontinued treatment due to an adverse reaction, compared with 3.5% of placebo-treated patients. The most common adverse reaction leading to discontinuation in at least 1% of the vilazodone hydrochloride-treated patients in the placebo-controlled studies was nausea (1.4%). Common adverse reactions in placebo-controlled MDD studies Table 2 shows the incidence of common adverse reactions occurring in ≥ 2% of vilazodone hydrochloride-treated patients and greater than the rate of placebo-treated patients in MDD Studies. There were no dose-related adverse reactions between 20 mg and 40 mg reported. Table 2: Common Adverse Reactions Occurring in ≥ 2% of Vilazodone Hydrochloride-treated Patients and Greater than the Rate of Placebo-Treated Patients System Organ Class Preferred Term Placebo N=967 Vilazodone Hydrochloride 20 mg/day N=288 Vilazodone Hydrochloride 40 mg/day N=978 1 Includes abdominal discomfort, abdominal pain upper, and abdominal pain.

ccurring in ≥ 2% of Vilazodone Hydrochloride-treated Patients and Greater than the Rate of Placebo-Treated Patients System Organ Class Preferred Term Placebo N=967 Vilazodone Hydrochloride 20 mg/day N=288 Vilazodone Hydrochloride 40 mg/day N=978 1 Includes abdominal discomfort, abdominal pain upper, and abdominal pain. 2 Includes headache and tension headache 3 Includes restlessness, akathisia, and restless legs syndrome Sexual adverse reactions are presented in Table 3 Gastrointestinal disorders Diarrhea 10% 26% 29% Nausea 7% 22% 24% Dry mouth 5% 8% 7% Vomiting 2% 4% 5% Abdominal pain1 3% 7% 4% Dyspepsia 2% 2% 3% Flatulence 1% 3% 3% Gastroenteritis 1% 1% 2% Abdominal distension 1% 2% 1% Nervous system disorders Headache2 14% 15% 14% Dizziness 5% 6% 8% Somnolence 2% 4% 5% Paresthesia 1% 1% 2% Psychiatric disorders Insomnia 2% 7% 6% Abnormal dreams 2% 2% 3% Restlessness3 1% 2% 3% General disorders Fatigue 3% 4% 3% Cardiac disorders Palpitations <1% 1% 2% Metabolism and nutrition disorders Increased appetite 1% 1% 3% Musculoskeletal and connective tissue disorders Arthralgia 1% 2% 1% Investigations Increased weight 1% 1% 2% Sexual adverse reactions Table 3 displays the most common sexual adverse reactions in the placebo-controlled MDD studies. Table 3: Common Sexual Adverse Reactions Occurring in ≥ 2% of Vilazodone Hydrochloride-treated Patients and Greater than the Rate of Placebo-Treated Patients − Not applicable *Includes abnormal orgasm and anorgasmia Preferred Term Males Females Placebo N=416 Vilazodone Hydrochloride 20 mg/day N=122 Vilazodone Hydrochloride 40 mg/day N=417 Placebo N=551 Vilazodone Hydrochloride 20 mg/day N=166 Vilazodone Hydrochloride 40 mg/day N=561 Abnormal Orgasm* <1% 2% 2% 0% 1% 1% Erectile dysfunction 1% 0% 3% - - - Libido decreased <1% 3% 4% <1% 2% 2% Ejaculation disorder 0% 1% 2% - - - Other adverse reactions observed in clinical studies The following list does not include reactions: 1) already listed in previous tables or elsewhere in labeling, 2) for which a drug cause was remote, 3) which were so general as to be uninformative, 4) which were not considered to have significant clinical implications, or 5) which occurred at a rate equal to or less than placebo. Reactions are categorized by body system according to the following definitions: frequent adverse reactions are those occurring in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1000 patients; rare reactions are those occurring in fewer than 1/1000 patients: Cardiac disorders: infrequent: ventricular extrasystoles Eye disorders: infrequent: dry eye, vision blurred, rare: cataracts Nervous System: frequent: sedation, tremor; infrequent: migraine Psychiatric disorders: infrequent: panic attack Skin and subcutaneous tissue disorders: infrequent: hyperhidrosis, night sweats 6.2 Post-marketing Experience The following adverse reactions have been identified during post-approval use of vilazodone hydrochloride. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure. Reports of adverse reactions temporally associated with vilazodone hydrochloride that have been received since market introduction and that are not listed above include the following: General Disorders and Administration Site Conditions : irritability Nervous System Disorders: sleep paralysis Psychiatric Disorders: hallucinations, suicide attempt, suicidal ideation Skin and subcutaneous tissue disorders: rash, generalized rash, urticaria, drug eruption Gastrointestinal System: acute pancreatitis

<table cellpadding="0pt" cellspacing="0pt" width="100%"><col width="27%"/><col width="21%"/><col width="26%"/><col width="26%"/><thead><tr><th align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <content styleCode="bold">System Organ Class</content> <content styleCode="bold">Preferred Term</content></th><th align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <content styleCode="bold">Placebo</content> <content styleCode="bold">N=967</content></th><th align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <content styleCode="bold">Vilazodone Hydrochloride</content> <content styleCode="bold">20 mg/day</content> <content styleCode="bold">N=288</content></th><th align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <content styleCode="bold">Vilazodone Hydrochloride</content> <content styleCode="bold">40 mg/day</content> <content styleCode="bold">N=978</content></th></tr></thead><tfoot><tr><td align="left" colspan="4" valign="top">1 Includes abdominal discomfort, abdominal pain upper, and abdominal pain.

le Toprule " valign="top"> <content styleCode="bold">Vilazodone Hydrochloride</content> <content styleCode="bold">40 mg/day</content> <content styleCode="bold">N=978</content></th></tr></thead><tfoot><tr><td align="left" colspan="4" valign="top">1 Includes abdominal discomfort, abdominal pain upper, and abdominal pain. </td></tr><tr><td align="left" colspan="4" valign="top">2 Includes headache and tension headache </td></tr><tr><td align="left" colspan="4" valign="top">3 Includes restlessness, akathisia, and restless legs syndrome </td></tr><tr><td align="left" colspan="4" valign="top">Sexual adverse reactions are presented in Table 3 </td></tr></tfoot><tbody><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph><content styleCode="bold">Gastrointestinal disorders</content></paragraph></td><td styleCode="Rrule Toprule Botrule " valign="top"/><td styleCode="Rrule Toprule Botrule " valign="top"/><td styleCode="Rrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Diarrhea </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>10% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>26% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>29% </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Nausea </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>7% </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 Lrule Botrule " valign="middle"><paragraph> Dry mouth </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>5% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>8% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>7% </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Vomiting </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>4% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>5% </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Abdominal pain1</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>3% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>7% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>4% </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>2% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>3% </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Flatulence </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>3% </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Gastroenteritis </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><par

rule " valign="middle"><paragraph>3% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>3% </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Gastroenteritis </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><par agraph>1% </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></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Abdominal distension </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 Botrule " valign="middle"><paragraph><content styleCode="bold">Nervous system disorders</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Headache2</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>14% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>15% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>14% </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Dizziness </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>5% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>6% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>8% </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Somnolence </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>4% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>5% </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Paresthesia </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1% </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></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Psychiatric disorders</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Insomnia </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>7% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>6% </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Abnormal dreams </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>3% </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " va

gn="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>2% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>3% </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " va lign="middle"><paragraph> Restlessness3</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>3% </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">General disorders</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Fatigue </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>3% </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 Botrule " valign="middle"><paragraph><content styleCode="bold">Cardiac disorders</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Palpitations </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>&lt;1% </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></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Metabolism and nutrition disorders</content></paragraph></td><td styleCode="Rrule Botrule " valign="middle"/><td styleCode="Rrule Botrule " valign="middle"/><td styleCode="Rrule Botrule " valign="middle"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Increased appetite </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1% </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></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Musculoskeletal and connective tissue disorders</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph> Arthralgia </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 Botrule " valign="middle"><paragraph><content styleCode="bold">Investigations</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Botrule Lrule " valign="middle"><paragraph> Increased weight </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1% </p

d styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Botrule Lrule " valign="middle"><paragraph> Increased weight </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1% </p aragraph></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></tr></tbody></table>

d styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/><td styleCode="Rrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Botrule Lrule " valign="middle"><paragraph> Increased weight </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="middle"><paragraph>1% </p aragraph></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></tr></tbody></table> <table cellpadding="0pt" cellspacing="0pt" width="100%"><col width="18%"/><col width="18%"/><col width="13%"/><col width="13%"/><col width="12%"/><col width="13%"/><col width="13%"/><tfoot><tr><td align="left" colspan="7" valign="top">&#x2212; Not applicable *Includes abnormal orgasm and anorgasmia </td></tr></tfoot><tbody><tr><td align="center" rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph> <content styleCode="bold">Preferred Term</content></paragraph></td><td align="center" colspan="3" styleCode="Rrule Botrule Toprule " valign="top"><paragraph><content styleCode="bold">Males</content></paragraph></td><td align="center" colspan="3" styleCode="Rrule Botrule Toprule " valign="top"><paragraph><content styleCode="bold">Females</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> <content styleCode="bold"> Placebo</content> <content styleCode="bold">N=416</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph> <content styleCode="bold">Vilazodone Hydrochloride 20 mg/day</content> <content styleCode="bold">N=122</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph> <content styleCode="bold">Vilazodone Hydrochloride</content> <content styleCode="bold">40 mg/day</content> <content styleCode="bold">N=417</content></paragraph></td><td styleCode="Rrule Botrule " valign="top"><paragraph> <content styleCode="bold">Placebo</content> <content styleCode="bold">N=551</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph> <content styleCode="bold">Vilazodone Hydrochloride 20 mg/day</content> <content styleCode="bold">N=166</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph> <content styleCode="bold">Vilazodone Hydrochloride</content> <content styleCode="bold">40 mg/day</content> <content styleCode="bold">N=561</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Abnormal Orgasm* </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;1% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1% </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Erectile dysfunction </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>- </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>- </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>- </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Libido decreased </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;1% </paragraph></td><td align="cen

- </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>- </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Libido decreased </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;1% </paragraph></td><td align="cen ter" styleCode="Rrule Botrule " valign="top"><paragraph>3% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>4% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;1% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2% </paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="top"><paragraph>Ejaculation disorder </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2% </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>- </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>- </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>- </paragraph></td></tr></tbody></table>

7 DRUG INTERACTIONS • CYP3A4 Inhibitors: The vilazodone hydrochloride dose should not exceed 20 mg once daily when co-administered with strong CYP3A4 inhibitors (, 7 ). • CYP3A4 Inducers: Consider increasing vilazodone hydrochloride dosage by 2-fold, up to 80 mg once-daily over 1 to 2 weeks when used concomitantly with strong CYP3A4 inducers for greater than 14 days (, 7 ). 7.1 Drugs Having Clinically Important Interactions With Vilazodone Hydrochloride Table 1: Clinically Important Drug Interactions with Vilazodone Hydrochloride Concomitant Drug Name or Drug Class Clinical Rationale Clinical Recommendation Monoamine Oxidase Inhibitors (MAOIs) The concomitant use of MAOIs and serotonergic drugs including vilazodone hydrochloride increases the risk of serotonin syndrome. Vilazodone hydrochloride is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [see Contraindications (4) , , and . Other Serotonergic Drugs The concomitant use of serotonergic drugs including vilazodone hydrochloride and other serotonergic drugs increases the risk of serotonin syndrome. Monitor patients for signs and symptoms of serotonin syndrome, particularly during vilazodone hydrochloride initiation. If serotonin syndrome occurs, consider discontinuation of vilazodone hydrochloride and/or concomitant serotonergic drugs [ ]. Antiplatelet Agents and Anticoagulants Serotonin release by platelets plays an important role in hemostasis. The concurrent use of an antiplatelet agent or anticoagulant with vilazodone hydrochloride may potentiate the risk of bleeding. Inform patients of the increased risk of bleeding with the concomitant use of vilazodone hydrochloride and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio (INR) when initiating, titrating, or discontinuing vilazodone hydrochloride [ ] . Strong CYP3A4 Inhibitors (e.g., itraconazole, clarithromycin, voriconazole) The concomitant use of vilazodone hydrochloride and strong CYP3A4 inhibitors increased the exposure of vilazodone compared to the use of vilazodone hydrochloride alone [ ]. The vilazodone hydrochloride dose should not exceed 20 mg once daily with the concomitant use of a strong CYP3A4 inhibitor [ , ]. Strong CYP3A4 Inducers (e.g., carbamazepine, phenytoin, rifampin) The concomitant use of vilazodone hydrochloride and strong CYP3A4 inducers decreased the exposure of vilazodone compared to the use of vilazodone hydrochloride alone [ ]. Based on clinical response, consider increasing the dosage of vilazodone hydrochloride, over 1 to 2 weeks inpatients taking strong CYP3A4 inducers for greater than 14 days [ ]. Digoxin Digoxin is a narrow therapeutic index drug. Concomitant use of vilazodone hydrochloride increased digoxin concentrations [ ] . Measure serum digoxin concentrations before initiating concomitant use of vilazodone hydrochloride. Continue monitoring and reduce digoxin dose as necessary. 7.2 Drugs Having No Clinically Important Interactions With Vilazodone Hydrochloride Based on pharmacokinetic studies, no dosage adjustment is required for drugs that are substrates of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and/or P-glycoprotein (except narrow therapeutic index drugs, e.g., digoxin), when vilazodone hydrochloride is administered concomitantly , .

<table cellpadding="0pt" cellspacing="0pt" width="100%"><caption>Table 1: Clinically Important Drug Interactions with Vilazodone Hydrochloride </caption><col width="33%"/><col width="33%"/><col width="33%"/><tbody><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph> <content styleCode="bold">Concomitant Drug Name or Drug Class</content></paragraph></td><td styleCode="Rrule Botrule Toprule " valign="middle"><paragraph> <content styleCode="bold">Clinical Rationale</content></paragraph></td><td styleCode="Rrule Botrule Toprule " valign="middle"><paragraph> <content styleCode="bold">Clinical Recommendation</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Monoamine Oxidase Inhibitors (MAOIs) </paragraph></td><td styleCode="Rrule Botrule " valign="middle"><paragraph>The concomitant use of MAOIs and serotonergic drugs including vilazodone hydrochloride increases the risk of serotonin syndrome. </paragraph></td><td styleCode="Rrule Botrule " valign="middle"><paragraph>Vilazodone hydrochloride is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue<content styleCode="italics"><linkHtml href="#_RefSection_4">[see Contraindications (4)</linkHtml>, </content>, and .</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Other Serotonergic Drugs </paragraph></td><td styleCode="Rrule Botrule " valign="middle"><paragraph>The concomitant use of serotonergic drugs including vilazodone hydrochloride and other serotonergic drugs increases the risk of serotonin syndrome. </paragraph></td><td styleCode="Rrule Botrule " valign="middle"><paragraph>Monitor patients for signs and symptoms of serotonin syndrome, particularly during vilazodone hydrochloride initiation. If serotonin syndrome occurs, consider discontinuation of vilazodone hydrochloride and/or concomitant serotonergic drugs <content styleCode="italics">[</content><content styleCode="italics">].</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Antiplatelet Agents and Anticoagulants </paragraph></td><td styleCode="Rrule Botrule " valign="middle"><paragraph>Serotonin release by platelets plays an important role in hemostasis. The concurrent use of an antiplatelet agent or anticoagulant with vilazodone hydrochloride may potentiate the risk of bleeding. </paragraph></td><td styleCode="Rrule Botrule " valign="middle"><paragraph>Inform patients of the increased risk of bleeding with the concomitant use of vilazodone hydrochloride and antiplatelet agents and anticoagulants.

platelet agent or anticoagulant with vilazodone hydrochloride may potentiate the risk of bleeding. </paragraph></td><td styleCode="Rrule Botrule " valign="middle"><paragraph>Inform patients of the increased risk of bleeding with the concomitant use of vilazodone hydrochloride and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio (INR) when initiating, titrating, or discontinuing vilazodone hydrochloride <content styleCode="italics">[</content><content styleCode="italics">]</content>.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Strong CYP3A4 Inhibitors (e.g., itraconazole, clarithromycin, voriconazole) </paragraph></td><td styleCode="Rrule Botrule " valign="middle"><paragraph>The concomitant use of vilazodone hydrochloride and strong CYP3A4 inhibitors increased the exposure of vilazodone compared to the use of vilazodone hydrochloride alone <content styleCode="italics">[</content><content styleCode="italics">].</content></paragraph></td><td styleCode="Rrule Botrule " valign="middle"><paragraph>The vilazodone hydrochloride dose should not exceed 20 mg once daily with the concomitant use of a strong CYP3A4 inhibitor <content styleCode="italics">[</content>, <content styleCode="italics">].</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Strong CYP3A4 Inducers (e.g., carbamazepine, phenytoin, rifampin) </paragraph></td><td styleCode="Rrule Botrule " valign="middle"><paragraph>The concomitant use of vilazodone hydrochloride and strong CYP3A4 inducers decreased the exposure of vilazodone compared to the use of vilazodone hydrochloride alone <content styleCode="italics">[</content><content styleCode="italics">].</content></paragraph></td><td styleCode="Rrule Botrule " valign="middle"><paragraph>Based on clinical response, consider increasing the dosage of vilazodone hydrochloride, over 1 to 2 weeks inpatients taking strong CYP3A4 inducers for greater than 14 days<content styleCode="italics"> [</content><content styleCode="italics">].</content></paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="middle"><paragraph>Digoxin </paragraph></td><td styleCode="Rrule Botrule " valign="middle"><paragraph>Digoxin is a narrow therapeutic index drug. Concomitant use of vilazodone hydrochloride increased digoxin concentrations <content styleCode="italics">[</content><content styleCode="italics">]</content>. </paragraph></td><td styleCode="Rrule Botrule " valign="middle"><paragraph>Measure serum digoxin concentrations before initiating concomitant use of vilazodone hydrochloride. Continue monitoring and reduce digoxin dose as necessary. </paragraph></td></tr></tbody></table>

8 USE IN SPECIFIC POPULATIONS Pregnancy: Third trimester use may increase risk for persistent pulmonary hypertension and withdrawal in the newborn (). 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 1-844-405- 6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants. Risk Summary There are no adequate and well-controlled studies of vilazodone hydrochloride in pregnant women. The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies. In animal reproduction studies, oral administration of vilazodone during the period of organogenesis at doses up to 48 and 17 times the maximum recommended human dose (MRHD) in rats and rabbits, respectively, resulted in decreased fetal body weight gain and delayed skeletal ossification but no teratogenic effects were observed. Decreased fetal body weight and delayed skeletal ossification were not observed at doses up to 10 and 4 times the MRHD in rats and rabbits, respectively [see Data] . Clinical Considerations Disease-associated maternal and/or embryo/fetal risk A prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. The women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants. Consider the risks of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. Fetal/Neonatal adverse reactions Exposure to SSRIs and SNRIs, including vilazodone hydrochloride, in late pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding, and/or persistent pulmonary hypertension of the newborn (PPHN). Monitor neonates who were exposed to vilazodone hydrochloride in the third trimester of pregnancy for PPHN and drug discontinuation syndrome [see Data)] . Data Human Data Third Trimester Exposure Neonates exposed to SSRIs or SNRIs late in the third trimester, have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. These findings are based on post-marketing reports. 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, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. In some cases, the clinical picture was consistent with serotonin syndrome [ ] . Exposure during late pregnancy to SSRIs may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN).

consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. In some cases, the clinical picture was consistent with serotonin syndrome [ ] . Exposure during late pregnancy to SSRIs may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in 1 to 2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. In a retrospective case-control study of 377 women whose infants were born with PPHN and 836 women whose infants were born healthy, the risk for developing PPHN was approximately six-fold higher for infants exposed to SSRIs after the 20th week of gestation compared to infants who had not been exposed to antidepressants during pregnancy. A study of 831,324 infants born in Sweden in 1997-2005 found a PPHN risk ratio of 2.4 (95% CI 1.2 to 4.3) associated with patient-reported maternal use of SSRIs “in early pregnancy” and a PPHN risk ratio of 3.6 (95% CI 1.2 to 8.3) associated with a combination of patient-reported maternal use of SSRIs “in early pregnancy” and an antenatal SSRI prescription “in later pregnancy.” Animal Data No teratogenic effects were observed when vilazodone was given to pregnant rats or rabbits during the period of organogenesis at oral doses up to 200 and 36 mg/kg/day, respectively. These doses are 48 and 17 times, in rats and rabbits, respectively, the maximum recommended human dose (MRHD) of 40 mg on a mg/m2 basis. Fetal body weight gain was reduced, and skeletal ossification was delayed in both rats and rabbits at these doses; these effects were not observed at doses up to 10 times the MRHD in rats or 4 times the MRHD in rabbits. When vilazodone was administered to pregnant rats at an oral dose of 30 times the MRHD during the period of organogenesis and throughout pregnancy and lactation, the number of live born pups was decreased. There was an increase in early postnatal pup mortality, and among surviving pups there was decreased body weight, delayed maturation, and decreased fertility in adulthood. There was some maternal toxicity at this dose. These effects were not seen at 6 times the MRHD. 8.2 Lactation Risk Summary There are no data on the presence of vilazodone in human milk, the effects of vilazodone on the breastfed infant, or the effects of the drug on milk production. However, vilazodone is excreted in rat milk [ see Data ]. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for vilazodone hydrochloride and any potential adverse effects on the breastfed child from vilazodone hydrochloride or from the underlying maternal condition. Data Animal Data Administration of vilazodone to lactating rats at an oral dose of 30 times the maximum recommended human dose (MRHD), resulted in early postnatal pup mortality, and among surviving pups there was decreased body weight and delayed maturation. 8.4 Pediatric Use The safety and effectiveness of vilazodone hydrochloride tablets have not been established in pediatric patients for the treatment of MDD. Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients, and . Juvenile Animal Toxicity Data In a juvenile animal study, male and female rats were treated with vilazodone (10, 50, and 200 mg/kg/day) starting on postnatal day (PND) 21 through 90. A delay in the age of attainment of vaginal patency (i.e. sexual maturation) was observed in females starting at 50 mg/kg/day with a No Observed Adverse Effect Level (NOAEL) of 10 mg/kg/day. Adverse behavioral effects (lack of habituation in an acoustic startle test) were observed in males at 200 mg/kg and females starting at 50 mg/kg both during drug treatment and the recovery periods.

ration) was observed in females starting at 50 mg/kg/day with a No Observed Adverse Effect Level (NOAEL) of 10 mg/kg/day. Adverse behavioral effects (lack of habituation in an acoustic startle test) were observed in males at 200 mg/kg and females starting at 50 mg/kg both during drug treatment and the recovery periods. The NOAEL for this finding was 50 mg/kg for males and 10 mg/kg for females. An 8% decrease in femur mineral density was observed in female rats at 200 mg/kg, compared to the control group. The NOAEL for this finding was 50 mg/kg. Pediatric information describing a clinical study in which efficacy was not demonstrated is approved for Allergan’s Viibryd (vilazodone hydrochloride) tablets. However, due to Allergan’s marketing exclusivity rights, this drug product is not labeled with that information. 8.5 Geriatric Use Based on a pharmacokinetic study, no dosage adjustment of vilazodone hydrochloride is recommended on the basis of age (see Figure 3). Results from pharmacokinetic study of a single 20 mg vilazodone hydrochloride dose in geriatric subjects (> 65 years-old) vs. younger subjects (24 to 55 years-old) demonstrated that the pharmacokinetics were generally similar between the two age groups . Clinical studies of vilazodone hydrochloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Of the 3,007 patients in clinical studies with vilazodone hydrochloride, 65 (2.2%) were 65 years of age or older, and 378 (12.6%) were 55 to 64 years of age. In general, dose selection for an elderly patient should be conservative, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Serotonergic antidepressants have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction . No other differences in adverse reactions were observed between geriatric and younger patients. 8.6 Use in Other Patient Populations No dosage adjustment of vilazodone hydrochloride is necessary on the basis of gender, renal function (mild to severe renal impairment, glomerular filtration rate: 15 to 90 mL/minute), or hepatic function (mild to severe hepatic impairment, Child-Pugh score: 5 to 15 .

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 1-844-405- 6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants. Risk Summary There are no adequate and well-controlled studies of vilazodone hydrochloride in pregnant women. The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies. In animal reproduction studies, oral administration of vilazodone during the period of organogenesis at doses up to 48 and 17 times the maximum recommended human dose (MRHD) in rats and rabbits, respectively, resulted in decreased fetal body weight gain and delayed skeletal ossification but no teratogenic effects were observed. Decreased fetal body weight and delayed skeletal ossification were not observed at doses up to 10 and 4 times the MRHD in rats and rabbits, respectively [see Data] . Clinical Considerations Disease-associated maternal and/or embryo/fetal risk A prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. The women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants. Consider the risks of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. Fetal/Neonatal adverse reactions Exposure to SSRIs and SNRIs, including vilazodone hydrochloride, in late pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding, and/or persistent pulmonary hypertension of the newborn (PPHN). Monitor neonates who were exposed to vilazodone hydrochloride in the third trimester of pregnancy for PPHN and drug discontinuation syndrome [see Data)] . Data Human Data Third Trimester Exposure Neonates exposed to SSRIs or SNRIs late in the third trimester, have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. These findings are based on post-marketing reports. 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, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. In some cases, the clinical picture was consistent with serotonin syndrome [ ] . Exposure during late pregnancy to SSRIs may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in 1 to 2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality.

picture was consistent with serotonin syndrome [ ] . Exposure during late pregnancy to SSRIs may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in 1 to 2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. In a retrospective case-control study of 377 women whose infants were born with PPHN and 836 women whose infants were born healthy, the risk for developing PPHN was approximately six-fold higher for infants exposed to SSRIs after the 20th week of gestation compared to infants who had not been exposed to antidepressants during pregnancy. A study of 831,324 infants born in Sweden in 1997-2005 found a PPHN risk ratio of 2.4 (95% CI 1.2 to 4.3) associated with patient-reported maternal use of SSRIs “in early pregnancy” and a PPHN risk ratio of 3.6 (95% CI 1.2 to 8.3) associated with a combination of patient-reported maternal use of SSRIs “in early pregnancy” and an antenatal SSRI prescription “in later pregnancy.” Animal Data No teratogenic effects were observed when vilazodone was given to pregnant rats or rabbits during the period of organogenesis at oral doses up to 200 and 36 mg/kg/day, respectively. These doses are 48 and 17 times, in rats and rabbits, respectively, the maximum recommended human dose (MRHD) of 40 mg on a mg/m2 basis. Fetal body weight gain was reduced, and skeletal ossification was delayed in both rats and rabbits at these doses; these effects were not observed at doses up to 10 times the MRHD in rats or 4 times the MRHD in rabbits. When vilazodone was administered to pregnant rats at an oral dose of 30 times the MRHD during the period of organogenesis and throughout pregnancy and lactation, the number of live born pups was decreased. There was an increase in early postnatal pup mortality, and among surviving pups there was decreased body weight, delayed maturation, and decreased fertility in adulthood. There was some maternal toxicity at this dose. These effects were not seen at 6 times the MRHD.

8.2 Lactation Risk Summary There are no data on the presence of vilazodone in human milk, the effects of vilazodone on the breastfed infant, or the effects of the drug on milk production. However, vilazodone is excreted in rat milk [ see Data ]. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for vilazodone hydrochloride and any potential adverse effects on the breastfed child from vilazodone hydrochloride or from the underlying maternal condition. Data Animal Data Administration of vilazodone to lactating rats at an oral dose of 30 times the maximum recommended human dose (MRHD), resulted in early postnatal pup mortality, and among surviving pups there was decreased body weight and delayed maturation.

8.4 Pediatric Use The safety and effectiveness of vilazodone hydrochloride tablets have not been established in pediatric patients for the treatment of MDD. Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients, and . Juvenile Animal Toxicity Data In a juvenile animal study, male and female rats were treated with vilazodone (10, 50, and 200 mg/kg/day) starting on postnatal day (PND) 21 through 90. A delay in the age of attainment of vaginal patency (i.e. sexual maturation) was observed in females starting at 50 mg/kg/day with a No Observed Adverse Effect Level (NOAEL) of 10 mg/kg/day. Adverse behavioral effects (lack of habituation in an acoustic startle test) were observed in males at 200 mg/kg and females starting at 50 mg/kg both during drug treatment and the recovery periods. The NOAEL for this finding was 50 mg/kg for males and 10 mg/kg for females. An 8% decrease in femur mineral density was observed in female rats at 200 mg/kg, compared to the control group. The NOAEL for this finding was 50 mg/kg. Pediatric information describing a clinical study in which efficacy was not demonstrated is approved for Allergan’s Viibryd (vilazodone hydrochloride) tablets. However, due to Allergan’s marketing exclusivity rights, this drug product is not labeled with that information.

8.5 Geriatric Use Based on a pharmacokinetic study, no dosage adjustment of vilazodone hydrochloride is recommended on the basis of age (see Figure 3). Results from pharmacokinetic study of a single 20 mg vilazodone hydrochloride dose in geriatric subjects (> 65 years-old) vs. younger subjects (24 to 55 years-old) demonstrated that the pharmacokinetics were generally similar between the two age groups . Clinical studies of vilazodone hydrochloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Of the 3,007 patients in clinical studies with vilazodone hydrochloride, 65 (2.2%) were 65 years of age or older, and 378 (12.6%) were 55 to 64 years of age. In general, dose selection for an elderly patient should be conservative, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Serotonergic antidepressants have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction . No other differences in adverse reactions were observed between geriatric and younger patients.

9.2 Abuse and Dependence Vilazodone hydrochloride has been systematically studied in animals and did not demonstrate abuse or dependence potential. While vilazodone hydrochloride has not been systematically studied in humans for its potential for abuse, there was no suggested evidence of drug-seeking behavior in the clinical studies.

10 OVERDOSAGE There is limited clinical trial experience regarding human overdose with vilazodone hydrochloride. The adverse reactions associated with overdose of vilazodone hydrochloride at doses of 200 to 280 mg (5 to 7 times the recommended dosage) as observed in clinical trials included serotonin syndrome, lethargy, restlessness, hallucinations, and disorientation. For current information on the management of poisoning or overdose, contact a poison control center at 1-800-222-1222. No specific antidotes for vilazodone are known. Removal of vilazodone by dialysis has not been studied; however, the high volume of distribution of vilazodone suggests that dialysis will not be effective in reducing vilazodone plasma concentrations.

11 DESCRIPTION Vilazodone hydrochloride tablets for oral administration contain polymorph Form IV vilazodone hydrochloride (HCl), a selective serotonin reuptake inhibitor and a 5HT1A receptor partial agonist. Vilazodone Hydrochloride is 2-benzofurancarboxamide, 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-1-piperazinyl]-, hydrochloride with a molecular formula of C 26 H 27 N 5 O 2 .HCl. Its molecular weight is 479.99 g/mol. The structural formula is: Vilazodone hydrochloride tablets are available as 10 mg, 20 mg, and 40 mg film-coated tablets containing 10 mg, 20 mg, and 40 mg of vilazodone HCl, respectively. In addition to the active ingredient, vilazodone hydrochloride tablets contain the following inactive ingredients: colloidal silicon dioxide, FD&C Blue #1 Aluminum Lake (40 mg only), Ferric Oxide Red (10 mg only) and FD&C Yellow #6 Aluminum Lake (20 mg only), lactose monohydrate, macrogol (polyethylene glycol), magnesium stearate, microcrystalline cellulose, opadry II blue (for 40 mg), opadry II pink (for 10 mg) and opadry II orange (for 20 mg), polyvinyl alcohol, polyethylene glycol, titanium dioxide, talc. vilazodone-str

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of action The mechanism of action of vilazodone in the treatment of major depressive disorder is not fully understood, but is thought to be related to its enhancement of serotonergic activity in the CNS through selective inhibition of serotonin reuptake. Vilazodone is also a partial agonist at serotonergic 5-HT 1A receptors; however, the net result of this action on serotonergic transmission and its role in vilazodone’s antidepressant effect are unknown. 12.2 Pharmacodynamics Vilazodone binds with high affinity to the serotonin reuptake site (Ki= 0.1 nM), but not to the norepinephrine (Ki=56 nM) or dopamine (Ki=37 nM) reuptake sites. Vilazodone potently and selectively inhibits reuptake of serotonin (IC 50 = 1.6 nM). Vilazodone also binds selectively with high affinity to 5-HT 1A receptors (IC 50 =2.1 nM) and is a 5-HT 1A receptor partial agonist. Cardiac Electrophysiology Treatment with vilazodone hydrochloride did not prolong the QTc interval. The effect of vilazodone hydrochloride [20, 40, 60, and 80 mg (2 times the recommended dosage)] on the QTc interval was evaluated in a randomized, placebo-, and active-controlled (moxifloxacin 400 mg), parallel-group, thorough QTc study in 157 healthy subjects. The study demonstrated an ability to detect small effects. The upper bound of the 90% confidence interval for the largest placebo-adjusted, baseline-corrected QTc interval was below 10 msec, based on the individual correction method (QTcI). Thus, at doses of 2 times the recommended dosage, vilazodone hydrochloride did not prolong the QTc interval to a clinically relevant extent. 12.3 Pharmacokinetics Vilazodone activity is due primarily to the parent drug. The pharmacokinetics of vilazodone (5 mg to 80 mg) are dose-proportional. Accumulation of vilazodone after administration of single vilazodone hydrochloride doses did not vary with dose, and steady-state was achieved in about 3 days. Elimination of vilazodone is primarily by hepatic metabolism with a terminal half-life of approximately 25 hours. At steady-state, after daily dosing of vilazodone hydrochloride 40 mg under fed conditions, the mean C max value was 156 ng/mL, and the mean AUC (0-24 hours) value was 1645 ng·h/mL. Absorption Vilazodone concentrations peaked at a median of 4 to 5 hours (T max ) after vilazodone hydrochloride administration and declined with a terminal half-life of approximately 25 hours. The absolute bioavailability of vilazodone was 72% with food. Vilazodone AUC and Cmax in the fasted state can be decreased by approximately 50% and 60%, respectively, compared to the fed state. Administration without food can result in inadequate drug concentrations and may reduce effectiveness. Co-administration of vilazodone hydrochloride with ethanol or with a proton pump inhibitor (pantoprazole) did not affect the rate or extent of vilazodone absorption. In addition, neither the Tmax nor terminal elimination rate of vilazodone was altered by co-administration with either pantoprazole or ethanol. Absorption is decreased by approximately 25% if vomiting occurs within 7 hours of ingestion; no replacement dose is needed. Distribution Vilazodone is widely distributed and approximately 96 to 99% protein-bound. Administration of vilazodone hydrochloride to a patient taking another drug that is highly protein bound may cause increased free concentrations of the other drug, because vilazodone is highly bound to plasma protein.

se is needed. Distribution Vilazodone is widely distributed and approximately 96 to 99% protein-bound. Administration of vilazodone hydrochloride to a patient taking another drug that is highly protein bound may cause increased free concentrations of the other drug, because vilazodone is highly bound to plasma protein. The interaction between vilazodone and other highly protein-bound drugs has not been evaluated. Metabolism and Elimination Vilazodone hydrochloride is extensively metabolized through CYP and non-CYP pathways (possibly by carboxylesterase), with only 1% of the dose recovered in the urine and 2% of the dose recovered in the feces as unchanged vilazodone. CYP3A4 is primarily responsible for its metabolism among CYP pathways, with minor contributions from CYP2C19 and CYP2D6. Drug Interaction Studies Figure 1 below includes the impact of other drugs on the pharmacokinetics of vilazodone [ see Drug Interactions (7 )]. Figure 1. Effect of Other Drugs on Vilazodone Pharmacokinetics In vitro studies indicate that vilazodone is unlikely to inhibit or induce the metabolism of substrates for CYP1A1, 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4 or 3A5, except for CYP2C8. The effect of vilazodone on CYP2C8 activity has not been tested in vivo . Figure 2 below includes the impact of vilazodone on the pharmacokinetics of other drugs in vivo . Figure 2. Impact of Vilazodone on Other Drug Pharmacokinetics Studies in Specific Populations: The presence of mild to severe renal impairment or mild to severe hepatic impairment did not affect the apparent clearance of vilazodone (see Figure 3). There were no pharmacokinetic differences of vilazodone in geriatric patients compared to younger patients, or between males and females (see Figure 3). Figure 3: Impact of Intrinsic Factors on Vilazodone Pharmacokinetics vilazodone-figure1 vilazodone-figure2 vilazodone-figure3

12.1 Mechanism of action The mechanism of action of vilazodone in the treatment of major depressive disorder is not fully understood, but is thought to be related to its enhancement of serotonergic activity in the CNS through selective inhibition of serotonin reuptake. Vilazodone is also a partial agonist at serotonergic 5-HT 1A receptors; however, the net result of this action on serotonergic transmission and its role in vilazodone’s antidepressant effect are unknown.

12.2 Pharmacodynamics Vilazodone binds with high affinity to the serotonin reuptake site (Ki= 0.1 nM), but not to the norepinephrine (Ki=56 nM) or dopamine (Ki=37 nM) reuptake sites. Vilazodone potently and selectively inhibits reuptake of serotonin (IC 50 = 1.6 nM). Vilazodone also binds selectively with high affinity to 5-HT 1A receptors (IC 50 =2.1 nM) and is a 5-HT 1A receptor partial agonist. Cardiac Electrophysiology Treatment with vilazodone hydrochloride did not prolong the QTc interval. The effect of vilazodone hydrochloride [20, 40, 60, and 80 mg (2 times the recommended dosage)] on the QTc interval was evaluated in a randomized, placebo-, and active-controlled (moxifloxacin 400 mg), parallel-group, thorough QTc study in 157 healthy subjects. The study demonstrated an ability to detect small effects. The upper bound of the 90% confidence interval for the largest placebo-adjusted, baseline-corrected QTc interval was below 10 msec, based on the individual correction method (QTcI). Thus, at doses of 2 times the recommended dosage, vilazodone hydrochloride did not prolong the QTc interval to a clinically relevant extent.

12.3 Pharmacokinetics Vilazodone activity is due primarily to the parent drug. The pharmacokinetics of vilazodone (5 mg to 80 mg) are dose-proportional. Accumulation of vilazodone after administration of single vilazodone hydrochloride doses did not vary with dose, and steady-state was achieved in about 3 days. Elimination of vilazodone is primarily by hepatic metabolism with a terminal half-life of approximately 25 hours. At steady-state, after daily dosing of vilazodone hydrochloride 40 mg under fed conditions, the mean C max value was 156 ng/mL, and the mean AUC (0-24 hours) value was 1645 ng·h/mL. Absorption Vilazodone concentrations peaked at a median of 4 to 5 hours (T max ) after vilazodone hydrochloride administration and declined with a terminal half-life of approximately 25 hours. The absolute bioavailability of vilazodone was 72% with food. Vilazodone AUC and Cmax in the fasted state can be decreased by approximately 50% and 60%, respectively, compared to the fed state. Administration without food can result in inadequate drug concentrations and may reduce effectiveness. Co-administration of vilazodone hydrochloride with ethanol or with a proton pump inhibitor (pantoprazole) did not affect the rate or extent of vilazodone absorption. In addition, neither the Tmax nor terminal elimination rate of vilazodone was altered by co-administration with either pantoprazole or ethanol. Absorption is decreased by approximately 25% if vomiting occurs within 7 hours of ingestion; no replacement dose is needed. Distribution Vilazodone is widely distributed and approximately 96 to 99% protein-bound. Administration of vilazodone hydrochloride to a patient taking another drug that is highly protein bound may cause increased free concentrations of the other drug, because vilazodone is highly bound to plasma protein. The interaction between vilazodone and other highly protein-bound drugs has not been evaluated. Metabolism and Elimination Vilazodone hydrochloride is extensively metabolized through CYP and non-CYP pathways (possibly by carboxylesterase), with only 1% of the dose recovered in the urine and 2% of the dose recovered in the feces as unchanged vilazodone. CYP3A4 is primarily responsible for its metabolism among CYP pathways, with minor contributions from CYP2C19 and CYP2D6. Drug Interaction Studies Figure 1 below includes the impact of other drugs on the pharmacokinetics of vilazodone [ see Drug Interactions (7 )]. Figure 1. Effect of Other Drugs on Vilazodone Pharmacokinetics In vitro studies indicate that vilazodone is unlikely to inhibit or induce the metabolism of substrates for CYP1A1, 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4 or 3A5, except for CYP2C8. The effect of vilazodone on CYP2C8 activity has not been tested in vivo . Figure 2 below includes the impact of vilazodone on the pharmacokinetics of other drugs in vivo . Figure 2. Impact of Vilazodone on Other Drug Pharmacokinetics Studies in Specific Populations: The presence of mild to severe renal impairment or mild to severe hepatic impairment did not affect the apparent clearance of vilazodone (see Figure 3). There were no pharmacokinetic differences of vilazodone in geriatric patients compared to younger patients, or between males and females (see Figure 3). Figure 3: Impact of Intrinsic Factors on Vilazodone Pharmacokinetics vilazodone-figure1 vilazodone-figure2 vilazodone-figure3

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Carcinogenicity studies were conducted in which B6C3F1 mice and Wistar rats were given oral doses of vilazodone up to 135 and 150 mg/kg/day, respectively, for 2 years. These doses are approximately 16.5 and 36 times the maximum recommended human dose (MRHD) of 40 mg, respectively, on a mg/m 2 basis. In mice, the incidence of hepatocellular carcinomas was increased in males at 16.5 times the MRHD; this finding was not observed at 5.5 times the MRHD. The incidence of malignant mammary gland tumors was numerically increased in females at 5.5 and 16.5 times the MRHD, with statistical significance at 16.5 the MRHD; this finding was not observed at 1.8 times the MRHD. Elevated prolactin levels were observed in a 2-week study of vilazodone administered at 5.5 and 33 times the MRHD. Increases in prolactin levels are known to cause mammary tumors in rodents. In the rat study, vilazodone was not carcinogenic in either sex at doses up to 36 times the MRHD. Mutagenesis Vilazodone was not mutagenic in the in vitro bacterial reverse mutation assay (Ames test). Vilazodone was negative in the in vitro V79/HGRPT mammalian cell forward mutation assay. Vilazodone was clastogenic in two in vitro mammalian cell chromosome aberration assays. However, vilazodone was negative for clastogenic activity in both an in vivo rat bone marrow chromosome aberration assay and a micronucleus test. Vilazodone was also negative in an in vivo / in vitro unscheduled DNA synthesis assay in rats. Impairment of Fertility Treatment of rats with vilazodone at a dose of 125 mg/kg, which is 30 times the MRHD of 40 mg on a mg/m 2 basis, caused impairment of male fertility with no effect on female fertility. Impaired male fertility was not observed at 6 times the MRHD.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Carcinogenicity studies were conducted in which B6C3F1 mice and Wistar rats were given oral doses of vilazodone up to 135 and 150 mg/kg/day, respectively, for 2 years. These doses are approximately 16.5 and 36 times the maximum recommended human dose (MRHD) of 40 mg, respectively, on a mg/m 2 basis. In mice, the incidence of hepatocellular carcinomas was increased in males at 16.5 times the MRHD; this finding was not observed at 5.5 times the MRHD. The incidence of malignant mammary gland tumors was numerically increased in females at 5.5 and 16.5 times the MRHD, with statistical significance at 16.5 the MRHD; this finding was not observed at 1.8 times the MRHD. Elevated prolactin levels were observed in a 2-week study of vilazodone administered at 5.5 and 33 times the MRHD. Increases in prolactin levels are known to cause mammary tumors in rodents. In the rat study, vilazodone was not carcinogenic in either sex at doses up to 36 times the MRHD. Mutagenesis Vilazodone was not mutagenic in the in vitro bacterial reverse mutation assay (Ames test). Vilazodone was negative in the in vitro V79/HGRPT mammalian cell forward mutation assay. Vilazodone was clastogenic in two in vitro mammalian cell chromosome aberration assays. However, vilazodone was negative for clastogenic activity in both an in vivo rat bone marrow chromosome aberration assay and a micronucleus test. Vilazodone was also negative in an in vivo / in vitro unscheduled DNA synthesis assay in rats. Impairment of Fertility Treatment of rats with vilazodone at a dose of 125 mg/kg, which is 30 times the MRHD of 40 mg on a mg/m 2 basis, caused impairment of male fertility with no effect on female fertility. Impaired male fertility was not observed at 6 times the MRHD.

14 CLINICAL STUDIES The efficacy of vilazodone hydrochloride as a treatment for major depressive disorder was demonstrated in four multicenter, randomized, double-blind, placebo-controlled studies in adult (18 to 70 years of age) outpatients who met the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria for MDD. Three 8-week studies evaluated the efficacy of vilazodone hydrochloride 40 mg (Studies 1 to 3) and one 10-week study (Study 4) evaluated the efficacy of vilazodone hydrochloride 20 mg and 40 mg (see Table 5). In these studies, patients were randomized to either 20 mg or 40 mg, or placebo once daily with food. Patients were either titrated over 1 week to a dose of 20 mg daily or over 2 weeks to a dose of 40 mg once daily of vilazodone hydrochloride with food. Vilazodone hydrochloride was superior to placebo in the improvement of depressive symptoms as measured by the change from baseline to endpoint visit in the Montgomery-Asberg Depression Rating Scale (MADRS) total score for both doses. The MADRS is a ten-item, clinician-rated scale used to assess severity of depressive symptoms. Scores on the MADRS range from 0 to 60, with higher scores indicating more severe depression. Clinical Global Impression - Severity (CGI-S) was evaluated in Studies 3 and 4. Vilazodone hydrochloride 20 mg and 40 mg demonstrated superiority over placebo as measured by improvement in CGI-S score. Table 2: Summary of Results for the Primary Efficacy Endpoint - MADRS Total Score SD = standard deviation; SE = standard error; LS Mean = least-square mean; CI = confidence interval a based on patients who took study medication and had baseline and post baseline MADRS assessments b difference (drug minus placebo) in least-square mean change from baseline to endpoint * All vilazodone hydrochloride treatment dose groups remained statistically significant compared with placebo after adjusting for multiplicity Study Number Treatment Group Number of Patients a Mean Baseline Score (SD) LS Mean Change from Baseline (SE) Placebo-subtracted Difference b (95% CI) Study 1 Vilazodone hydrochloride 40 mg/day 198 30.8 (3.90) -12.9 (0.77) -3.2 (-5.2, -1.3) Placebo 199 30.7 (3.93) -9.6 (0.76) Study 2 Vilazodone hydrochloride 40 mg/day 231 31.9 (3.50) -13.3 (0.90) -2.5 (-4.4, -0.6) Placebo 232 32.0 (3.63) -10.8 (0.90) Study 3 Vilazodone hydrochloride 40 mg/day 253 30.7 (3.3) -16.1 (0.64) -5.1 (-6.9, -3.3) Placebo 252 30.9 (3.3) -11.0 (0.65) Vilazodone hydrochloride 20 mg/day* 288 31.3 (3.5) -17.3 (0.63) -2.6 (-4.3, -0.8) Study 4 Vilazodone hydrochloride 40 mg/day* 284 31.2 (3.8) -17.6 (0.65) -2.8 (-4.6, -1.1) Placebo 281 31.4 (3.8) -14.8 (0.62) Baseline demographics information were generally similar across all treatment groups. Examination of population subgroups based on age (there were few patients over 65), gender and race did not reveal any clear evidence of differential responsiveness.

<table ID="_RefID0EBWBG" cellpadding="0pt" cellspacing="0pt" width="100%"><caption>Table 2: Summary of Results for the Primary Efficacy Endpoint - MADRS Total Score </caption><col width="14%"/><col width="17%"/><col width="17%"/><col width="17%"/><col width="17%"/><col width="17%"/><tfoot><tr><td align="left" colspan="6" valign="top">SD = standard deviation; SE = standard error; LS Mean = least-square mean; CI = confidence interval </td></tr><tr><td align="left" colspan="6" valign="top">^a based on patients who took study medication and had baseline and post baseline MADRS assessments ^b difference (drug minus placebo) in least-square mean change from baseline to endpoint </td></tr><tr><td align="left" colspan="6" valign="top">^*All vilazodone hydrochloride treatment dose groups remained statistically significant compared with placebo after adjusting for multiplicity </td></tr></tfoot><tbody><tr><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Study</content> <content styleCode="bold">Number</content></paragraph></td><td align="center" styleCode="Rrule Botrule Toprule " valign="top"><paragraph><content styleCode="bold">Treatment Group</content></paragraph></td><td align="center" styleCode="Rrule Botrule Toprule " valign="top"><paragraph><content styleCode="bold">Number of Patients ^a</content></paragraph></td><td align="center" styleCode="Rrule Botrule Toprule " valign="top"><paragraph><content styleCode="bold">Mean Baseline Score (SD)</content></paragraph></td><td align="center" styleCode="Rrule Botrule Toprule " valign="top"><paragraph><content styleCode="bold">LS Mean Change from Baseline (SE)</content></paragraph></td><td align="center" styleCode="Rrule Botrule Toprule " valign="top"><paragraph><content styleCode="bold">Placebo-subtracted Difference ^b</content> <content styleCode="bold"> (95% CI)</content></paragraph></td></tr><tr><td align="center" rowspan="2" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Study 1 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>Vilazodone hydrochloride 40 mg/day </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>198 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>30.8 (3.90) </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>-12.9 (0.77) </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>-3.2 (-5.2, -1.3) </paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Placebo </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>199 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>30.7 (3.93) </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>-9.6 (0.76) </paragraph></td><td styleCode="Rrule Botrule " valign="top"/></tr><tr><td align="center" rowspan="2" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Study 2 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>Vilazodone hydrochloride 40 mg/day </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>231 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>31.9 (3.50) </paragraph></td><td align="

align="center" styleCode="Rrule Botrule " valign="top"><paragraph>Vilazodone hydrochloride 40 mg/day </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>231 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>31.9 (3.50) </paragraph></td><td align=" center" styleCode="Rrule Botrule " valign="top"><paragraph>-13.3 (0.90) </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>-2.5 (-4.4, -0.6) </paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Placebo </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>232 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>32.0 (3.63) </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>-10.8 (0.90) </paragraph></td><td styleCode="Rrule Botrule " valign="top"/></tr><tr><td align="center" rowspan="2" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Study 3 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>Vilazodone hydrochloride 40 mg/day </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>253 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>30.7 (3.3) </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>-16.1 (0.64) </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>-5.1 (-6.9, -3.3) </paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Placebo </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>252 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>30.9 (3.3) </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>-11.0 (0.65) </paragraph></td><td styleCode="Rrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"/><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>Vilazodone hydrochloride 20 mg/day* </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>288 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>31.3 (3.5) </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>-17.3 (0.63) </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>-2.6 (-4.3, -0.8) </paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Study 4 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>Vilazodone hydrochloride 40 mg/day* </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>284 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>31.2 (3.8) </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>-17.6 (0.65) </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>-2.8 (-4.6, -1.1) </paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="top"/><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>Placebo </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>281 </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>31.4 (3.8) </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>-14.8 (0.62) </paragraph></td><td styleCode="Rrule Botrule " valign="top"/></tr></tbody></table>

16 HOW SUPPLIED/STORAGE AND HANDLING Vilazodone hydrochloride tablets are supplied in the following configurations: 20 mg: Orange colored, ellipse shaped, biconvex, film coated tablets, debossed with “MV” on one side and “15” on other side, 68788-8734-3 30-count bottles 40 mg: Blue colored, ellipse shaped, biconvex, film coated tablets, debossed with “MV” on one side and “16” on other side. 68788-8735-330-count bottles Vilazodone hydrochloride tablets should be stored at 25°C (77°F); excursions permitted from 15°C to 30°C (59°F 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 . Dosage and Administration Instruct patients to take vilazodone hydrochloride with food and to follow prescribed dosage instructions [see Dosage and Administration (2.1 , , , )]. Serotonin Syndrome Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of vilazodone hydrochloride with other serotonergic drugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and 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). Patients should contact their health care provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome and Drug Interactions (7 )] . Increased Risk of Bleeding Inform patients about the concomitant use of vilazodone hydrochloride tablets with aspirin, NSAIDs, other antiplatelet drugs, warfarin, or other anticoagulants because the combined use of drugs that interfere with serotonin reuptake (e.g., vilazodone hydrochloride) and these medications has been associated with an increased risk of bleeding. Advise them 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. 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 . Discontinuation Syndrome Advise patients not to abruptly discontinue vilazodone hydrochloride tablets and to discuss any tapering regimen with their healthcare provider. Adverse reactions can occur when vilazodone hydrochloride tablets are discontinued[] . Seizures Caution patients about using vilazodone hydrochloride if they have a history of a seizure disorder . Sexual Dysfunction Advise patients that use of vilazodone hydrochloride 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 . Allergic Reactions Advise patients to notify their healthcare provider if they develop an allergic reaction such as rash, hives, swelling, or difficulty breathing . Concomitant Medications Advise patients to inform their health care providers if they are taking, or plan to take any prescription or over-the-counter medications since there is a potential for interactions Pregnancy • Advise pregnant women to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with vilazodone hydrochloride tablets . • Advise patients that vilazodone hydrochloride tablets use late 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) .

reatment with vilazodone hydrochloride tablets . • Advise patients that vilazodone hydrochloride tablets use late 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) . • Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to vilazodone hydrochloride tablets during pregnancy . Manufactured by: MSN Laboratories Private Limited Telangana – 509 228, INDIA Distributed by: Novadoz Pharmaceuticals LLC Piscataway, NJ 08854-3714 Issued on: June 2023 Repackaged By: Preferred Pharmaceuticals Inc.

MEDICATION GUIDE Vilazodone Hydrochloride Tablets, for oral use (vil-AZ-oh-done) What is the most important information I should know about vilazodone hydrochloride tablets? Vilazodone hydrochloride tablets may cause serious side effects, including: • Increased risk of suicidal thoughts or actions in some children, adolescents, and young adults. Vilazodone hydrochloride tablets and other antidepressant medicines may increase suicidal thoughts or actions in some people 24 years of age and younger, especially within the first few months of treatment or when the dose is changed.Vilazodone hydrochloride tablets are not for use in children. • Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions. S ome people may have a higher risk of having suicidal thoughts or actions. These include people who have (or have a family history of) depression, bipolar illness (also called manic-depressive illness) or have a history of suicidal thoughts or 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 dose is changed. • Call your healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings. • 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 or your family member 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, being angry or violent • thoughts about suicide or dying • new or worse depression • new or worse anxiety • panic attacks • feeling agitated or restless • new or worse irritability • trouble sleeping (insomnia) • an extreme increase in activity or talking (mania) • other unusual changes in behavior or mood What are vilazodone hydrochloride tablets? Vilazodone hydrochloride tablets are a prescription medicine used to treat a certain type of depression called Major Depressive Disorder (MDD) in adults. It is not known if vilazodone hydrochloride tablets are safe and effective for use in children for the treatment of MDD. Who should not take vilazodone hydrochloride tablets? Do not take vilazodone hydrochloride 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 Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid or intravenous methylene blue. Do not start taking an MAOI for at least 14 days after you stop treatment with vilazodone hydrochloride. Before taking vilazodone hydrochloride tablets, tell your healthcare provider about all your medical conditions, including if you: • have or have a family history of suicide, depression, bipolar disorder, mania or hypomania • have or had bleeding problems • have or had seizures or convulsions • have high pressure in the eye (glaucoma) • have low sodium levels in your blood • drink alcohol • are pregnant or plan to become pregnant.

ncluding if you: • have or have a family history of suicide, depression, bipolar disorder, mania or hypomania • have or had bleeding problems • have or had seizures or convulsions • have high pressure in the eye (glaucoma) • have low sodium levels in your blood • drink alcohol • are pregnant or plan to become pregnant. Taking vilazodone hydrochloride tablets late in pregnancy may lead to an increased risk of certain problems in your newborn. Talk to your healthcare provider about the risks to your baby if you take vilazodone hydrochloride tablets during pregnancy. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with vilazodone hydrochloride tablets. • There is a pregnancy registry for females who are exposed to vilazodone hydrochloride pregnancy. The purpose of the registry is to collect information about the health of females exposed to vilazodone hydrochloride and their baby. If you become pregnant during treatment with vilazodone hydrochloride, talk to your healthcare provider about registering with the National Pregnancy Registry for Antidepressants. You can register by calling 1-844-405-6185. • are breastfeeding or plan to breastfeed. It is not known if vilazodone hydrochloride passes into breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with vilazodone hydrochloride tablets. Tell your healthcare provider about all the medicines that you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Vilazodone hydrochloride and some medicines may affect each other causing possible serious side effects. Vilazodone hydrochloride may affect the way other medicines work and other medicines may affect the way vilazodone hydrochloride works. Especially tell your healthcare provider if you take: • MAOIs • medicines used to treat migraine headaches known as triptans • tricyclic antidepressants • fentanyl • lithium • tramadol • tryptophan • buspirone • amphetamines • St. John's Wort • medicines that can affect blood clotting such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) and warfarin • diuretics • medicines used to treat mood, anxiety, psychotic or thought disorders, including selective serotonin reuptake inhibitors (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 vilazodone hydrochloride tablets with your other medicines. Do not start or stop any other medicines during treatment vilazodone hydrochloride tablets without talking to your healthcare provider first. Stopping vilazodone hydrochloride tablets suddenly may cause you to have serious side effects. See, "What are the possible side effects of vilazodone hydrochloride 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 vilazodone hydrochloride tablets? • Take vilazodone hydrochloride tablets exactly as your healthcare provider tell you to. Do not change your dose or stop taking vilazodone hydrochloride tablets without first talking to your healthcare provider. • Your healthcare provider may need to change the dose of vilazodone hydrochloride until it is the right dose for you. • Take vilazodone hydrochloride tablets 1 time each day with food. • If you miss a dose of vilazodone hydrochloride tablets, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of vilazodone hydrochloride tablets at the same time.

tablets 1 time each day with food. • If you miss a dose of vilazodone hydrochloride tablets, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of vilazodone hydrochloride tablets at the same time. • If you take too much vilazodone hydrochloride tablets, call your healthcare provider or poison control center at 1-800-222-1222 right away, or get emergency treatment right away. What should I avoid while taking vilazodone hydrochloride tablets? • Do not drive, operate heavy machinery, or do other dangerous activities until you know how vilazodone hydrochloride tablets affects you. Vilazodone hydrochloride tablets can cause sleepiness or may affect your ability to make decisions, think clearly, or react quickly. • Avoid drinking alcohol during treatment with vilazodone hydrochloride tablets. What are the possible side effects of vilazodone hydrochloride tablets? Vilazodone hydrochloride tablets may cause serious side effects, including: • See, "What is the most important information I should know about vilazodone hydrochloride tablets?’’ • Serotonin Syndrome. A potentially life-threatening problem called serotonin syndrome can happen when vilazodone hydrochloride tablets are taken with certain other medicines. See, "Who should not take vilazodone hydrochloride tablets?" Stop taking vilazodone hydrochloride tablets and 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 • seeing or hearing things that are not real (hallucinations) • confusion • coma • fast heart beat • blood pressure changes • dizziness • sweating • flushing • high body temperature (hyperthermia) • tremors, stiff muscles, or muscle twitching • loss of coordination • seizures • nausea, vomiting, diarrhea • Increased risk of bleeding. Taking vilazodone hydrochloride tablets with aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), warfarin or blood thinners may add to this risk. Tell your healthcare provider right away about any unusual bleeding or bruising. • Mania or hypomania (manic episodes) in people who have a history of bipolar disorder. Symptoms may include: • greatly increased energy • severe trouble sleeping • racing thoughts • reckless behavior • unusually grand ideas • excessive happiness or irritability • talking more or faster than usual • Discontinuation syndrome. Suddenly stopping vilazodone hydrochloride tablets may cause you to have serious side effects. Your healthcare provider may want to decrease your dose slowly. Symptoms may include: • nausea • sweating • changes in your mood • headache • irritability and agitation • tiredness • dizziness • problems sleeping • electric shock sensation (paresthesia) • hypomania • anxiety • ringing in your ears (tinnitus) • confusion • seizures • Seizures (convulsions). • Eye problems (angle-closure glaucoma): vilazodone hydrochloride tablets may cause a certain type of eye problem called angle-closure glaucoma. Call your healthcare provider if you have changes in your vision or eye pain. • Low sodium levels in your blood (hyponatremia). Low sodium levels in your blood may be serious and may cause death. Elderly people may be at greater risk for this. Signs and Symptoms of low sodium levels in your blood may include: • headache • difficulty concentrating • memory changes • confusion • weakness and unsteadiness on your feet which can lead to falls In severe or more sudden cases, signs and symptoms include: • hallucinations (seeing or hearing things that are not real) • fainting • seizures • coma • respiratory arrest • death • Sexual problems (dysfunction).

concentrating • memory changes • confusion • weakness and unsteadiness on your feet which can lead to falls In severe or more sudden cases, signs and symptoms include: • hallucinations (seeing or hearing things that are not real) • fainting • seizures • coma • respiratory arrest • death • Sexual problems (dysfunction). Taking selective serotonin reuptake inhibitors (SSRIs), including vilazodone hydrochloride tablets, may cause sexual problems.Symptoms in males may include: • delayed ejaculation or inability to have an ejaculation • problems getting or keeping an erection • decreased sex drive Symptoms in females may include: • decreased sex drive • 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 vilazodone hydrochloride tablets. There may be treatments your healthcare provider can suggest. The most common side effects of vilazodone hydrochloride tablets include diarrhea, nausea or vomiting, trouble sleeping. These are not all the possible side effects of vilazodone hydrochloride 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 vilazodone hydrochloride tablets? • Store vilazodone hydrochloride tablets at room temperature between 68°F to 77°F (20°C to 25°C). • Keep vilazodone hydrochloride tablets and all medicines out of the reach of children. General information about the safe and effective use of vilazodone hydrochloride tablets. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use vilazodone hydrochloride tablets for a condition for which it was not prescribed. Do not give vilazodone hydrochloride 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 vilazodone hydrochloride that is written for healthcare professionals. What are the ingredients in vilazodone hydrochloride tablets? Active ingredient: vilazodone hydrochloride Inactive ingredients: colloidal silicon dioxide, FD&C Blue #1 Aluminum Lake (40 mg only), Ferric Oxide Red (10 mg only) and FD&C Yellow #6 Aluminum Lake (20 mg only), lactose monohydrate, macrogol (polyethylene glycol), magnesium stearate, microcrystalline cellulose, opadry II blue (for 40 mg), opadry II pink (for 10 mg) and opadry II orange (for 20 mg), polyvinyl alcohol, polyethylene glycol, titanium dioxide, talc. This Medication Guide has been approved by the U.S. Food and Drug Administration. Manufactured by: MSN Laboratories Private Limited Telangana – 509 228, INDIA Distributed by: Novadoz Pharmaceuticals LLC Piscataway, NJ 08854-3714 Issued on: June 2023 Repackaged By: Preferred Pharmaceuticals Inc.