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WARNING: LITHIUM TOXICITY Lithium toxicity is closely related to serum lithium concentrations, and can occur at doses close to therapeutic concentrations. Facilities for prompt and accurate serum lithium determinations should be available before initiating treatment [see Dosage and Administration (2.3) , Warnings and Precautions (5.1) ]. WARNING: LITHIUM TOXICITY See full prescribing information for complete boxed warning. Lithium toxicity is closely related to serum lithium concentrations, and can occur at doses close to therapeutic concentrations. Facilities for prompt and accurate serum lithium determinations should be available before initiating therapy (2.3 , 5.1) .

1 INDICATIONS AND USAGE Lithium is a mood-stabilizing agent indicated as monotherapy for the treatment of bipolar I disorder: Treatment of acute manic and mixed episodes in patients 7 years and older [see Clinical Studies (14) ] Maintenance treatment in patients 7 years and older [see Clinical Studies (14) ] Lithium is a mood-stabilizing agent indicated as monotherapy for the treatment of bipolar I disorder: Treatment of acute manic and mixed episodes in patients 7 years and older (1) Maintenance treatment in patients 7 years and older (1)

2 DOSAGE AND ADMINISTRATION Recommended starting dosage for adults and pediatric patients over 30 kg (2.2) : Capsules: 300 mg, three times daily Recommended starting dosage for pediatric patients 20 to 30 kg (2.2) : Capsules: 300 mg twice daily Obtain serum lithium concentration assay after 3 days, drawn 12 hours after the last oral dose and regularly until patient is stabilized. Acute Manic or Mixed Episodes (patients 7 years and older): Titrate to serum lithium concentrations 0.8 to 1.2 mEq/L (2.2) . Maintenance Treatment for Bipolar I Disorder (patients 7 years and older): Titrate to serum lithium concentrations 0.8 to 1 mEq/L (2.2) . Pre-treatment Screening: Evaluate renal function, vital signs, electrolytes, thyroid function, concurrent medications, and pregnancy status (2.1) . Mild to Moderate Renal Impairment (CLer 30 to 89 mL/min): Start with dosages less than those for patients with normal renal function, titrate slowly with frequent monitoring (2.5) . Severe Renal Impairment (CLer < 30 mL/min): Avoid use of lithium (2.5) . 2.1 Pre-treatment Screening Before initiating treatment with lithium, renal function, vital signs, serum electrolytes, and thyroid function should be evaluated. Concurrent medications should be assessed, and if the patient is a woman of childbearing potential, pregnancy status and potential should be considered. 2.2 Recommended Dosage See Table 1 for dosage recommendations for acute and maintenance treatment of bipolar I disorder in adult and pediatric patients (7 to 17 years). Obtain serum lithium concentration assay after 3 days, drawn 12 hours after the last oral dose and regularly until patient is stabilized. Fine hand tremor, polyuria, and thirst may occur during initial therapy for the acute manic phase and may persist throughout treatment. Nausea and general discomfort may also appear during the first few days of lithium administration. These adverse reactions may subside with continued treatment, concomitant administration with food, or temporary reduction or cessation of dosage. Table 1. Lithium Dosing for Bipolar I Disorder Patient Group Formulation Starting Dose Dose Titration Acute Goal Maintenance Goal Serum Level Usual Dose Serum Level Usual Dose Adult and Pediatric Patients over 30 kg Capsules 300 mg three times daily 300 mg every 3 days 0.8 to 1.2 mEq/L 600 mg two to three times daily 0.8 to 1 mEq/L 300 to 600 mg two to three times daily Pediatric Patients 20 to 30 kg Capsules 300 mg twice daily 300 mg weekly 600 to 1500 mg in divided doses daily 600 to 1200 mg in divided doses daily 2.3 Serum Lithium Monitoring Blood samples for serum lithium determination should be drawn immediately prior to the next dose when lithium concentrations are relatively stable (i.e., 12 hours after the previous dose). Total reliance must not be placed on serum concentrations alone. Accurate patient evaluation requires both clinical and laboratory analysis. In addition to regular monitoring of serum lithium concentrations for patients on maintenance treatment, serum lithium concentrations should be monitored after any change in dosage, concurrent medication (e.g., diuretics, non-steroidal anti-inflammatory drugs, renin-angiotensin system antagonists, or metronidazole), marked increase or decrease in routinely performed strenuous physical activity (such as an exercise program) and in the event of a concomitant disease [see Boxed Warning , Warnings and Precautions (5.1) , Drug Interactions (7.1) ].

roidal anti-inflammatory drugs, renin-angiotensin system antagonists, or metronidazole), marked increase or decrease in routinely performed strenuous physical activity (such as an exercise program) and in the event of a concomitant disease [see Boxed Warning , Warnings and Precautions (5.1) , Drug Interactions (7.1) ]. Patients abnormally sensitive to lithium may exhibit toxic signs at serum concentrations that are within what is considered the therapeutic range. Geriatric patients often respond to reduced dosage, and may exhibit signs of toxicity at serum concentrations ordinarily tolerated by other patients [see Specific Populations (8.5) ]. 2.4 Dosage Adjustments during Pregnancy and the Postpartum Period If the decision is made to continue lithium treatment during pregnancy, monitor serum lithium concentrations and adjust the dosage as needed in a pregnant woman because renal lithium clearance increases during pregnancy. Avoid sodium restriction or diuretic administration. To decrease the risk of postpartum lithium intoxication, decrease or discontinue lithium therapy two to three days before the expected delivery date to reduce neonatal concentrations and reduce the risk of maternal lithium intoxication due to the change in vascular volume which occurs during delivery. At delivery, vascular volume rapidly decreases and the renal clearance of lithium may decrease to pre-pregnancy concentrations. Restart treatment at the preconception dose when the patient is medically stable after delivery with careful monitoring of serum lithium concentrations [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ]. 2.5 Dosage Adjustments for Patients with Renal Impairment Start patients with mild to moderately impaired renal function (creatinine clearance 30 to 89 mL/min evaluated by Cockcroft-Gault) with dosages less than those for patients with normal renal function [see Dosage and Administration (2.2) ]. Titrate slowly while frequently monitoring serum lithium concentrations and monitoring for signs of lithium toxicity. Lithium is not recommended for use in patients with severe renal impairment (creatinine clearance less than 30 mL/min evaluated by Cockcroft-Gault) [see Use in Specific Populations (8.6) ].

3 DOSAGE FORMS AND STRENGTHS Each 150 mg capsule for oral administration contains: lithium carbonate, USP 150 mg and is a two piece light gray hard gelatin capsules (size ‘4’) imprinted with ‘150’ on the body and ‘G220’ on the cap. Each 300 mg capsule for oral administration contains: lithium carbonate, USP 300 mg and is a two piece pink hard gelatin capsules (size ‘2’) imprinted with ‘300’ on the body and ‘G221’ on the cap. Each 600 mg capsule for oral administration contains: lithium carbonate, USP 600 mg and is a two piece hard gelatin capsules (size ‘0’ elongated) pink colored cap and light gray colored body imprinted with ‘600’ on the body and ‘G222’ on the cap. Capsules: 150 mg, 300 mg, 600 mg of lithium carbonate, USP (3)

4 CONTRAINDICATIONS Lithium is contraindicated in patients with known hypersensitivity to any inactive ingredient in the lithium carbonate capsule [see Adverse Reactions (6) ]. Known hypersensitivity to any inactive ingredient in the drug product. (4)

5 WARNINGS AND PRECAUTIONS Lithium-Induced Polyuria: May develop during initiation of treatment. Increases risk of lithium toxicity. Educate patient to avoid dehydration. Monitor for lithium toxicity and metabolic acidosis. Discontinue lithium or treat with amiloride as a therapeutic agent (5.2) . Hyponatremia: Symptoms are more severe with faster-onset hyponatremia. Dehydration from protracted sweating, diarrhea, or elevated temperatures from infection increases risk of hyponatremia and lithium toxicity. Educate patients on maintaining a normal diet with salt and staying hydrated. Monitor for and treat hyponatremia and lithium toxicity, which may necessitate a temporary reduction or cessation of lithium and infusion of serum sodium (5.3) . Lithium-Induced Chronic Kidney Disease: Associated with structural changes in patients on chronic lithium therapy. Monitor kidney function during treatment with lithium (5.4) . Encephalopathic Syndrome: Increased risk in patients treated with lithium and an antipsychotic. Monitor routinely for changes to cognitive function (5.5) . Hypothyroidism and Hyperthyroidism: Monitor thyroid function regularly (5.7) . Hypercalcemia and Hyperparathyroidism: Associated with long-term lithium use. Monitor serum calcium (5.8) . 5.1 Lithium Toxicity The toxic concentrations for lithium (≥1.5 mEq/L) are close to the therapeutic range (0.8 to 1.2mEq/L). Some patients abnormally sensitive to lithium may exhibit toxic signs at serum concentrations that are considered within the therapeutic range [see Boxed Warning , Dosage and Administration (2.3) ]. Lithium may take up to 24 hours to distribute into brain tissue, so occurrence of acute toxicity symptoms may be delayed. Neurological signs of lithium toxicity range from mild neurological adverse reactions such as fine tremor, lightheadedness, lack of coordination, and weakness; to moderate manifestations like giddiness, apathy, drowsiness, hyperreflexia, muscle twitching, ataxia, blurred vision, tinnitus, and slurred speech; and severe manifestations such as clonus, confusion, seizure, coma, and death. In rare cases, neurological sequelae may persist despite discontinuing lithium treatment and may be associated with cerebellar atrophy. Cardiac manifestations involve electrocardiographic changes, such as prolonged QT interval, ST and T-wave changes and myocarditis. Renal manifestations include urine concentrating defect, nephrogenic diabetes insipidus, and renal failure. Respiratory manifestations include dyspnea, aspiration pneumonia, and respiratory failure. Gastrointestinal manifestations include nausea, vomiting, diarrhea, and bloating. No specific antidote for lithium poisoning is known [see Overdosage (10) ]. The risk of lithium toxicity is increased by: Recent onset of concurrent febrile illness Concomitant administration of drugs which increase lithium serum concentrations by pharmacokinetic interactions or drugs affecting kidney function [see Drug Interactions (7) ]. Acute ingestion Impaired renal function Volume depletion or dehydration Significant cardiovascular disease Changes in electrolyte concentrations (especially sodium and potassium) Monitor for signs and symptoms of lithium toxicity. If symptoms occur, decrease dosage or discontinue lithium treatment.

Interactions (7) ]. Acute ingestion Impaired renal function Volume depletion or dehydration Significant cardiovascular disease Changes in electrolyte concentrations (especially sodium and potassium) Monitor for signs and symptoms of lithium toxicity. If symptoms occur, decrease dosage or discontinue lithium treatment. 5.2 Lithium-Induced Polyuria Chronic lithium treatment may be associated with diminution of renal concentrating ability, occasionally presenting as nephrogenic diabetes insipidus, with polyuria and polydipsia. The concentrating defect and natriuretic effect characteristic of this condition may develop within weeks of lithium initiation. Lithium can also cause renal tubular acidosis, resulting in hyperchloremic metabolic acidosis. Such patients should be carefully managed to avoid dehydration with resulting lithium retention and toxicity. This condition is usually reversible when lithium is discontinued, although for patients treated with long-term lithium, nephrogenic diabetes insipidus may be only partly reversible upon discontinuation of lithium. Amiloride may be considered as a therapeutic agent for lithium-induced nephrogenic diabetes insipidus. 5.3 Hyponatremia Lithium can cause hyponatremia by decreasing sodium reabsorption by the renal tubules, leading to sodium depletion. Therefore, it is essential for patients receiving lithium treatment to maintain a normal diet, including salt, and an adequate fluid intake (2500 to 3000 mL) at least during the initial stabilization period. Decreased tolerance to lithium has also been reported to ensue from protracted sweating or diarrhea and, if such occur, supplemental fluid and salt should be administered under careful medical supervision and lithium intake reduced or suspended until the condition is resolved. In addition, concomitant infection with elevated temperatures may also necessitate a temporary reduction or cessation of medication. Symptoms are also more severe with faster-onset hyponatremia. Mild hyponatremia (i.e., serum Na > 120 mEq/L) can be asymptomatic. Below this threshold, clinical signs are usually present, consisting mainly of changes in mental status, such as altered personality, lethargy, and confusion. For more severe hyponatremia (serum Na < 115 mEq/L), stupor, neuromuscular hyperexcitability, hyperreflexia, seizures, coma, and death can result. During treatment of hyponatremia, serum sodium should not be elevated by more than 10 to 12 mEq/L in 24 hours, or 18 mEq/L in 48 hours. In the case of severe hyponatremia where severe neurologic symptoms are present, a faster infusion rate to correct serum sodium concentration may be needed. Patients rapidly treated or with serum sodium <120mEq/L are more at risk of developing osmotic demyelination syndrome (previously called central pontine myelinolysis). Occurrence is more common among patients with alcoholism, undernutrition, or other chronic debilitating illness. Common signs include flaccid paralysis, dysarthria. In severe cases with extended lesions patients may develop a locked-in syndrome (generalized motor paralysis). Damage often is permanent. If neurologic symptoms start to develop during treatment of hyponatremia, serum sodium correction should be suspended to mitigate the development of permanent neurologic damage. 5.4 Lithium-Induced Chronic Kidney Disease The predominant form of chronic renal disease associated with long-term lithium treatment is a chronic tubulointerstitial nephropathy (CTIN). The biopsy findings in patients with lithium induced CTIN include tubular atrophy, interstitial fibrosis, sclerotic glomeruli, tubular dilation, and nephron atrophy with cyst formation. The relationship between renal function and morphologic changes and their association with lithium treatment has not been established.

The biopsy findings in patients with lithium induced CTIN include tubular atrophy, interstitial fibrosis, sclerotic glomeruli, tubular dilation, and nephron atrophy with cyst formation. The relationship between renal function and morphologic changes and their association with lithium treatment has not been established. CTIN patients might present with nephrotic proteinuria (>3g/dL), worsening renal insufficiency and/or nephrogenic diabetes insipidus. Postmarketing cases consistent with nephrotic syndrome in patients with or without CTIN have also been reported. The biopsy findings in patients with nephrotic syndrome include minimal change disease and focal segmental glomerulosclerosis. The discontinuation of lithium in patients with nephrotic syndrome has resulted in remission of nephrotic syndrome. Kidney function should be assessed prior to and during lithium treatment. Routine urinalysis and other tests may be used to evaluate tubular function (e.g., urine specific gravity or osmolality following a period of water deprivation, or 24-hour urine volume) and glomerular function (e.g., serum creatinine, creatinine clearance, or proteinuria). During lithium treatment, progressive or sudden changes in renal function, even within the normal range, indicate the need for re-evaluation of treatment. 5.5 Encephalopathic Syndrome An encephalopathic syndrome, characterized by weakness, lethargy, fever, tremulousness and confusion, extrapyramidal symptoms, leukocytosis, elevated serum enzymes, BUN and fasting blood glucose, has occurred in patients treated with lithium and an antipsychotic. In some instances, the syndrome was followed by irreversible brain damage. Because of a possible causal relationship between these events and the concomitant administration of lithium and antipsychotics, patients receiving such combined treatment should be monitored closely for early evidence of neurological toxicity and treatment discontinued promptly if such signs appear. This encephalopathic syndrome may be similar to or the same as neuroleptic malignant syndrome (NMS). 5.6 Serotonin Syndrome Lithium can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, triptans, tricyclic antidepressants, fentanyl, tramadol, tryptophan, buspirone, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [see Drug Interactions (7.1) ] . 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). Monitor all patients taking lithium for the emergence of serotonin syndrome. Discontinue treatment with lithium and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of lithium with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms. 5.7 Hypothyroidism or Hyperthyroidism Lithium is concentrated within the thyroid and can inhibit thyroid synthesis and release which can lead to hypothyroidism. Where hypothyroidism exists, careful monitoring of thyroid function during lithium stabilization and maintenance allows for correction of changing thyroid parameters, if any.

ism or Hyperthyroidism Lithium is concentrated within the thyroid and can inhibit thyroid synthesis and release which can lead to hypothyroidism. Where hypothyroidism exists, careful monitoring of thyroid function during lithium stabilization and maintenance allows for correction of changing thyroid parameters, if any. Where hypothyroidism occurs during lithium stabilization and maintenance, supplemental thyroid treatment may be used. Paradoxically, some cases of hyperthyroidism have been reported including Grave’s disease, toxic multinodular goiter and silent thyroiditis. Monitor thyroid function before the initiation of treatment, at three months and every six to twelve months while treatment is ongoing. If serum thyroid tests warrant concern, monitoring should occur more frequently. 5.8 Hypercalcemia and Hyperparathyroidism Long-term lithium treatment is associated with persistent hyperparathyroidism and hypercalcemia. When clinical manifestations of hypercalcemia are present, lithium withdrawal and change to another mood stabilizer may be necessary. Hypercalcemia may not resolve upon discontinuation of lithium, and may require surgical intervention. Lithium-induced cases of hyperparathyroidism are more often multiglandular compared to standard cases. False hypercalcemia due to plasma volume depletion resulting from nephrogenic diabetes insipidus should be excluded in individuals with mildly increased serum calcium. Monitor serum calcium concentrations regularly. 5.9 Unmasking of Brugada Syndrome There have been postmarketing reports of a possible association between treatment with lithium and the unmasking of Brugada Syndrome. Brugada Syndrome is a disorder characterized by abnormal electrocardiographic (ECG) findings and a risk of sudden death. Lithium should be avoided in patients with Brugada Syndrome or those suspected of having Brugada Syndrome. Consultation with a cardiologist is recommended if: (1) treatment with lithium is under consideration for patients suspected of having Brugada Syndrome or patients who have risk factors for Brugada Syndrome, e.g., unexplained syncope, a family history of Brugada Syndrome, or a family history of sudden unexplained death before the age of 45 years, (2) patients who develop unexplained syncope or palpitations after starting lithium treatment. 5.10 Pseudotumor Cerebri Cases of pseudotumor cerebri (increased intracranial pressure and papilledema) have been reported with lithium use. If undetected, this condition may result in enlargement of the blind spot, constriction of visual fields and eventual blindness due to optic atrophy. Consider discontinuing lithium if this syndrome occurs.

6 ADVERSE REACTIONS The following adverse reactions are described in greater detail in other sections: Acute Lithium Toxicity [see Warnings and Precautions (5.1) ] Lithium-Induced Polyuria [see Warnings and Precautions (5.2) ] Hyponatremia [see Warnings and Precautions (5.3) ] Lithium-Induced Chronic Kidney Disease [see Warnings and Precautions (5.4) ] Encephalopathic Syndrome [see Warnings and Precautions (5.5) ] Serotonin Syndrome [see Warnings and Precautions (5.6) ] Hypothyroidism or Hyperthyroidism [see Warnings and Precautions (5.7) ] Hypercalcemia and Hyperparathyroidism [see Warnings and Precautions (5.8) ] Unmasking of Brugada Syndrome [see Warnings and Precautions (5.9) ] Pseudotumor Cerebri [see Warnings and Precautions (5.10) ] Common Adverse Reactions: Adult Patients: fine hand tremor, polyuria, mild thirst, nausea, general discomfort during initial treatment (6) Pediatric Patients (7 to 17 years): nausea/vomiting, polyuria, thyroid abnormalities, tremor, thirst/polydipsia, dizziness, rash/dermatitis, ataxia/gait disturbance, decreased appetite, and blurry vision (6) To report SUSPECTED ADVERSE REACTIONS, contact Glenmark Pharmaceuticals Inc., USA at 1 (888) 721-7115 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Pediatric Patients (7 to 17 years): Bipolar I Disorder : The following findings are based on an 8-week, placebo-controlled study for acute manic or mixed episodes of bipolar I disorder in pediatric patients 7 to 17 years (N= 81). In this study, lithium was administered at daily doses ranging from 300 to 3600 (mean dose 1483 mg ± 584) with serum levels ranging from 0 to 2 (mean level 0.98 mEq/L ± 0.47). Common Adverse Reactions (incidence ≥ 5% and at least twice the rate of placebo) : nausea/vomiting, polyuria, thyroid abnormalities, tremor, thirst/polydipsia, dizziness, rash/dermatitis, ataxia/gait disturbance, decreased appetite, and blurry vision. Adverse Reactions Occurring at an Incidence of 2% or More in Lithium-Treated Pediatric Patients : Adverse reactions associated with the use of lithium (incidence of 2% or greater, rounded to the nearest percent, and lithium incidence greater than placebo) that occurred during acute therapy (up to 8-weeks in pediatric patients with bipolar disorder) are shown in Table 3. Table 3: Adverse Reactions Reported in 2% or More of Pediatric Patients on Lithium and That Occurred at Greater Incidence Than in the Placebo Group in the 8-Week Acute Bipolar Trial System Organ Class/ Preferred Term Placebo N=28 % Lithium N=53 % Gastrointestinal Disorders Nausea/vomiting 29 57 General Disorders Fatigue 4 26 Genitourinary Disorders Polyuria (Including Enuresis) 14 38 Investigations Increased TSH 0 25 Metabolism and nutrition disorders Thirst/polydipsia 11 28 Decreased appetite 4 9 Nervous system disorders Ataxia/gait disturbance 0 13 Blurry vision 0 9 Disorientation 0 6 Dizziness 7 23 Tremor 7 32 Skin and subcutaneous tissue disorders Rash/dermatitis 0 13 Adult Patients: The following adverse reactions have been identified following use of lithium.

Thirst/polydipsia 11 28 Decreased appetite 4 9 Nervous system disorders Ataxia/gait disturbance 0 13 Blurry vision 0 9 Disorientation 0 6 Dizziness 7 23 Tremor 7 32 Skin and subcutaneous tissue disorders Rash/dermatitis 0 13 Adult Patients: The following adverse reactions have been identified following use of lithium. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Central Nervous System: tremor, muscle hyperirritability (fasciculations, twitching, clonic movements of whole limbs), hypertonicity, ataxia, choreoathetotic movements, hyperactive deep tendon reflexes, extrapyramidal symptoms including acute dystonia, cogwheel rigidity, blackout spells, epileptiform seizures, slurred speech, dizziness, vertigo, downbeat nystagmus, incontinence of urine or feces, somnolence, psychomotor retardation, restlessness, confusion, stupor, coma, tongue movements, tics, tinnitus, hallucinations, poor memory, slowed intellectual functioning, startled response, worsening of organic brain syndromes, myasthenic syndromes (rarely). EEG Changes: diffuse slowing, widening of frequency spectrum, potentiation and disorganization of background rhythm. Cardiovascular: conduction disturbance (mostly sinus node dysfunction with possibly severe sinus bradycardia and sinoatrial block), ventricular tachyarrhythmia, peripheral vasculopathy (resembling Raynaud’s Syndrome). ECG Changes: reversible flattening, isoelectricity or rarely inversion of T-waves, prolongation of the QTc interval. Gastrointestinal: anorexia, nausea, vomiting, diarrhea, gastritis, salivary gland swelling, abdominal pain, excessive salivation, flatulence, indigestion. Genitourinary: glycosuria, decreased creatinine clearance, albuminuria, oliguria, and symptoms of nephrogenic diabetes insipidus including polyuria, thirst, and polydipsia. Dermatologic: drying and thinning of hair, alopecia, anesthesia of skin, chronic folliculitis, xerosis cutis, psoriasis onset or exacerbation, generalized pruritus with or without rash, cutaneous ulcers, angioedema, drug reaction with eosinophilia and systemic symptoms (DRESS). Autonomic Nervous System: blurred vision, dry mouth, impotence/sexual dysfunction. Miscellaneous: fatigue, lethargy, transient scotoma, exopthalmos, dehydration, weight loss, leukocytosis, headache, transient hyperglycemia, hypermagnesemia, excessive weight gain, edematous swelling of ankles or wrists, dysgeusia/taste distortion (e.g., metallic or salty taste), thirst, swollen lips, tightness in chest, swollen and/or painful joints, fever, polyarthralgia, and dental caries.

<table width="100%"><caption>Table 3: Adverse Reactions Reported in 2% or More of Pediatric Patients on Lithium and That Occurred at Greater Incidence Than in the Placebo Group in the 8-Week Acute Bipolar Trial</caption><colgroup><col width="37%"/><col width="33%"/><col width="30%"/></colgroup><tbody><tr><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">System Organ Class/</content></paragraph><paragraph><content styleCode="bold">Preferred Term</content></paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Placebo N=28</content></paragraph><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Lithium N=53</content></paragraph><paragraph><content styleCode="bold">%</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Gastrointestinal Disorders</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="top"/><td styleCode="Rrule Lrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Nausea/vomiting</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>29</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>57</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">General Disorders</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="top"/><td styleCode="Rrule Lrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Fatigue</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>26</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Genitourinary Disorders</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="top"/><td styleCode="Rrule Lrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Polyuria (Including Enuresis)</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>38</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Investigations</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="top"/><td styleCode="Rrule Lrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Increased TSH</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>25</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Metabolism and nutrition disorders</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="top"/><td styleCode="Rrule Lrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Thirst/polydipsia</paragraph></td><td align="center" styleCode=

ntent styleCode="bold">Metabolism and nutrition disorders</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="top"/><td styleCode="Rrule Lrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Thirst/polydipsia</paragraph></td><td align="center" styleCode= "Rrule Lrule Botrule " valign="top"><paragraph>11</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>28</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Decreased appetite</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>9</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Nervous system disorders</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="top"/><td styleCode="Rrule Lrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Ataxia/gait disturbance</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>13</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Blurry vision</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>9</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Disorientation</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>6</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Dizziness</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>7</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>23</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Tremor</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>7</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>32</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Skin and subcutaneous tissue disorders</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="top"/><td styleCode="Rrule Lrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Botrule Lrule " valign="top"><paragraph> Rash/dermatitis</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule " valign="top"><paragraph>13</paragraph></td></tr></tbody></table>

7 DRUG INTERACTIONS Diuretics, NSAID, renin-angiotensin system antagonists, or metronidazole may increase lithium serum concentrations. Recommend frequent monitoring of serum lithium concentration and adjust dosage when necessary. (2.3 , 7.1) Serotonergic Agents: Increased risk of serotonin syndrome when co-administered with lithium. (5.6 , 7.1) Antipsychotics: There have been reports of neurologic adverse reactions in patients treated with lithium and an antipsychotic, ranging from extrapyramidal symptoms to neuroleptic malignant syndrome. (5.5 , 7.1) 7.1 Drugs Having Clinically Important Interactions with Lithium Table 4: Clinically Important Drug Interactions with Lithium Diuretics Clinical Impact: Diuretic-induced sodium loss may reduce lithium clearance and increase serum lithium concentrations. Intervention: More frequent monitoring of serum electrolyte and lithium concentrations. Reduce lithium dosage based on serum lithium concentration and clinical response [see Dosage and Administration (2.3) , Warning and Precautions (5.3) ] . Non-Steroidal Anti-inflammatory Drugs (NSAID) Clinical Impact: NSAID decrease renal blood flow, resulting in decreased renal clearance and increased serum lithium concentrations. Intervention: More frequent serum lithium concentration monitoring. Reduce lithium dosage based on serum lithium concentration and clinical response [see Dosage and Administration (2.3) ] . Renin-Angiotensin System Antagonists Clinical Impact: Concomitant use increase steady-state serum lithium concentrations. Intervention: More frequent monitoring of serum lithium concentration. Reduce lithium dosage based on serum lithium concentration and clinical response [see Dosage and Administration (2.3) ] . Serotonergic Drugs Clinical Impact: Concomitant use can precipitate serotonin syndrome. Intervention: Monitor patients for signs and symptoms of serotonin syndrome, particularly during lithium initiation. If serotonin syndrome occurs, consider discontinuation of lithium and/or concomitant serotonergic drugs [see Warnings and Precautions (5.6) ] . Nitroimidazole Antibiotics Clinical Impact: Concomitant use may increase serum lithium concentrations due to reduced renal clearance. Intervention: More frequent monitoring of serum lithium concentration. Reduce lithium dosage based on serum lithium concentration and clinical response [see Dosage and Administration (2.3) ] . Acetazolamide, Urea, Xanthine Preparations, Alkalinizing Agents Clinical Impact: Concomitant use can lower serum lithium concentrations by increasing urinary lithium excretion. Intervention: More frequent serum lithium concentration monitoring. Increase lithium dosage based on serum lithium concentration and clinical response [see Dosage and Administration (2.3) ] . Methyldopa, Phenytoin and Carbamazepine Clinical Impact: Concomitant use may increase risk of adverse reactions of these drugs. Intervention: Monitor patients closely for adverse reactions of methyldopa, phenytoin, and carbamazepine. Iodide Preparations Clinical Impact: Concomitant use may produce hypothyroidism. Intervention: Monitor patients for signs or symptoms of hypothyroidism [see Warnings and Precautions (5.7) ] . Calcium Channel Blocking Agents (CCB) Clinical Impact: Concomitant use may increase the risk of neurologic adverse reactions in the form of ataxia, tremors, nausea, vomiting, diarrhea and/or tinnitus. Intervention: Monitor for neurologic adverse reactions.

ptoms of hypothyroidism [see Warnings and Precautions (5.7) ] . Calcium Channel Blocking Agents (CCB) Clinical Impact: Concomitant use may increase the risk of neurologic adverse reactions in the form of ataxia, tremors, nausea, vomiting, diarrhea and/or tinnitus. Intervention: Monitor for neurologic adverse reactions. Atypical and Typical Antipsychotic Drugs Clinical Impact: Reports of neurotoxic reactions in patients treated with both lithium and an antipsychotic, ranging from extrapyramidal symptoms to neuroleptic malignant syndrome, as well as reports of an encephalopathic syndrome in few patients treated with concomitant therapy [see Warnings and Precautions (5.5) ] . Intervention: Monitor for neurologic adverse reactions. Sodium-Glucose Cotransporter 2 (SGLT2) inhibitor Clinical Impact: Concomitant use of lithium with an SGLT2 inhibitor may decrease serum lithium concentrations. Intervention: Monitor serum lithium concentration more frequently during SGLT2 inhibitor initiation and dosage changes. Neuromuscular Blocking Agents Clinical Impact: Lithium may prolong the effects of neuromuscular blocking agents. Intervention: Monitor for prolonged paralysis.

<table width="100.38%"><caption>Table 4: Clinically Important Drug Interactions with Lithium</caption><colgroup><col width="21%"/><col width="79%"/></colgroup><tbody><tr><td colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">Diuretics</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Clinical Impact:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Diuretic-induced sodium loss may reduce lithium clearance and increase serum lithium concentrations.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Intervention:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>More frequent monitoring of serum electrolyte and lithium concentrations. Reduce lithium dosage based on serum lithium concentration and clinical response <content styleCode="italics">[see <linkHtml href="#ID_5ed0658e-7fc3-443a-b145-e43595336725">Dosage and Administration (2.3)</linkHtml>, <linkHtml href="#ID_a085b83f-f7bb-43f0-9cdc-59abd5399d9b">Warning and Precautions (5.3)</linkHtml>] </content>. </paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Non-Steroidal Anti-inflammatory Drugs (NSAID)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Clinical Impact:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>NSAID decrease renal blood flow, resulting in decreased renal clearance and increased serum lithium concentrations.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Intervention:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>More frequent serum lithium concentration monitoring. Reduce lithium dosage based on serum lithium concentration and clinical response <content styleCode="italics">[see <linkHtml href="#ID_5ed0658e-7fc3-443a-b145-e43595336725">Dosage and Administration (2.3)</linkHtml>] </content>. </paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Renin-Angiotensin System Antagonists</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Clinical Impact:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Concomitant use increase steady-state serum lithium concentrations.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Intervention:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>More frequent monitoring of serum lithium concentration. Reduce lithium dosage based on serum lithium concentration and clinical response <content styleCode="italics">[see <linkHtml href="#ID_5ed0658e-7fc3-443a-b145-e43595336725">Dosage and Administration (2.3)</linkHtml>] </content>.

trule " valign="middle"><paragraph>More frequent monitoring of serum lithium concentration. Reduce lithium dosage based on serum lithium concentration and clinical response <content styleCode="italics">[see <linkHtml href="#ID_5ed0658e-7fc3-443a-b145-e43595336725">Dosage and Administration (2.3)</linkHtml>] </content>. </paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Serotonergic Drugs</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Clinical Impact:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Concomitant use can precipitate serotonin syndrome.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Intervention:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Monitor patients for signs and symptoms of serotonin syndrome, particularly during lithium initiation. If serotonin syndrome occurs, consider discontinuation of lithium and/or concomitant serotonergic drugs <content styleCode="italics">[see <linkHtml href="#ID_0373b2cf-f4dc-4885-b883-4bb84de17de1">Warnings and Precautions (5.6)</linkHtml>] </content>. </paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Nitroimidazole Antibiotics</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Clinical Impact:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Concomitant use may increase serum lithium concentrations due to reduced renal clearance.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Intervention:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>More frequent monitoring of serum lithium concentration. Reduce lithium dosage based on serum lithium concentration and clinical response <content styleCode="italics">[see <linkHtml href="#ID_5ed0658e-7fc3-443a-b145-e43595336725">Dosage and Administration (2.3)</linkHtml>] </content>. </paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Acetazolamide, Urea, Xanthine Preparations, Alkalinizing Agents</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Clinical Impact:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Concomitant use can lower serum lithium concentrations by increasing urinary lithium excretion.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Intervention:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>More frequent serum lithium concentration monitoring. Increase lithium dosage based on serum lithium concentration and clinical response <content styleCode="italics">[see <linkHtml href="#ID_5ed0658e-7fc3-443a-b145-e43595336725">Dosage and Administration (2.3)</linkHtml>] </content>.

otrule " valign="middle"><paragraph>More frequent serum lithium concentration monitoring. Increase lithium dosage based on serum lithium concentration and clinical response <content styleCode="italics">[see <linkHtml href="#ID_5ed0658e-7fc3-443a-b145-e43595336725">Dosage and Administration (2.3)</linkHtml>] </content>. </paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Methyldopa, Phenytoin and Carbamazepine</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Clinical Impact:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Concomitant use may increase risk of adverse reactions of these drugs.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Intervention:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Monitor patients closely for adverse reactions of methyldopa, phenytoin, and carbamazepine.</paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Iodide Preparations</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Clinical Impact:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Concomitant use may produce hypothyroidism.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Intervention:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Monitor patients for signs or symptoms of hypothyroidism <content styleCode="italics">[see <linkHtml href="#ID_58d1337d-296c-443a-ae0d-2870b2021459">Warnings and Precautions (5.7)</linkHtml>] </content>. </paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Calcium Channel Blocking Agents (CCB)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Clinical Impact:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Concomitant use may increase the risk of neurologic adverse reactions in the form of ataxia, tremors, nausea, vomiting, diarrhea and/or tinnitus.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Intervention:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Monitor for neurologic adverse reactions.</paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Atypical and Typical Antipsychotic Drugs</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Clinical Impact:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Reports of neurotoxic reactions in patients treated with both lithium and an antipsychotic, ranging from extrapyramidal symptoms to neuroleptic malignant syndrome, as well as reports of an encephalopathic syndrome in few patients treated with concomitant therapy <content styleCode="italics">[see <linkHtml href="#ID_d0216ef8-8770-42ce-880d-10c1191bf948">Warnings and Precautions (5.5)</linkHtml>] </content>.

c, ranging from extrapyramidal symptoms to neuroleptic malignant syndrome, as well as reports of an encephalopathic syndrome in few patients treated with concomitant therapy <content styleCode="italics">[see <linkHtml href="#ID_d0216ef8-8770-42ce-880d-10c1191bf948">Warnings and Precautions (5.5)</linkHtml>] </content>. </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Intervention:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Monitor for neurologic adverse reactions.</paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Sodium-Glucose Cotransporter 2 (SGLT2) inhibitor</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Clinical Impact:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Concomitant use of lithium with an SGLT2 inhibitor may decrease serum lithium concentrations.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Intervention:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Monitor serum lithium concentration more frequently during SGLT2 inhibitor initiation and dosage changes.</paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Neuromuscular Blocking Agents</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Clinical Impact:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Lithium may prolong the effects of neuromuscular blocking agents.</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="middle"><paragraph><content styleCode="italics">Intervention:</content></paragraph></td><td styleCode="Rrule Botrule Lrule " valign="middle"><paragraph>Monitor for prolonged paralysis.</paragraph></td></tr></tbody></table>

8 USE IN SPECIFIC POPULATIONS Pregnancy: May cause fetal and/or neonatal harm (8.1) Renal Impairment: Use caution during dose selection, starting with dosages less than those for patients with normal renal function while carefully monitoring for side effects (2.5 , 6) 8.1 Pregnancy Risk Summary: Lithium may cause harm when administered to a pregnant woman. Early voluntary reports to international birth registries suggested an increase in cardiovascular malformations, especially for Ebstein’s anomaly, with first trimester use of lithium. Subsequent case-control and cohort studies indicate that the increased risk for cardiac malformations is likely to be small; however, the data are insufficient to establish a drug-associated risk. There are concerns for maternal and/or neonatal lithium toxicity during late pregnancy and the postpartum period [see Clinical Considerations]. Published animal developmental and toxicity studies in mice and rats report an increased incidence of fetal mortality, decreased fetal weight, increased fetal skeletal abnormalities, and cleft palate (mouse fetuses only) with oral doses of lithium that produced serum concentrations similar to the human therapeutic range. Other published animal studies report adverse effects on embryonic implantation in rats after lithium administration. Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population(s) is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations: Dose Adjustments During Pregnancy and the Postpartum Period: If the decision is made to continue lithium treatment during pregnancy, serum lithium concentrations should be monitored and the dosage adjusted during pregnancy. Two to three days prior to delivery, lithium dosage should be decreased or discontinued to reduce the risk of maternal and/or neonatal toxicity. Lithium may be restarted in the post-partum period at preconception doses in medically stable patients as long as serum lithium levels are closely monitored [see Dosage and Administration (2.4) , Warnings and Precautions (5.1) ]. Fetal/Neonatal Adverse Reactions: Lithium toxicity may occur in neonates who were exposed to lithium in late pregnancy. A floppy baby syndrome including neurological, cardiac, and hepatic abnormalities that are similar to those seen with lithium toxicity in adults have been observed. Symptoms include hypotonia, respiratory distress syndrome, cyanosis, lethargy, feeding difficulties, depressed neonatal reflexes, neonatal depression, apnea, and bradycardia. Monitor neonates and provide supportive care until lithium is excreted and toxic signs disappear, which may take up to 14 days. Consider fetal echocardiography between 16 and 20 weeks gestation in a woman with first trimester lithium exposure because of the potential increased risk of cardiac malformations. 8.2 Lactation Risk Summary: Limited published data reports the presence of lithium carbonate in human milk with breast milk levels measured at 0.12 to 0.7 mEq or 40 to 45% of maternal plasma levels. Infants exposed to lithium during breastfeeding may have plasma levels that are 30 to 40% of maternal plasma levels.

ons. 8.2 Lactation Risk Summary: Limited published data reports the presence of lithium carbonate in human milk with breast milk levels measured at 0.12 to 0.7 mEq or 40 to 45% of maternal plasma levels. Infants exposed to lithium during breastfeeding may have plasma levels that are 30 to 40% of maternal plasma levels. Signs and symptoms of lithium toxicity such as hypertonia, hypothermia, cyanosis, and ECG changes have been reported in some breastfed neonates and infants. Increased prolactin levels have been measured in lactating women, but the effects on milk production are not known. Breastfeeding is not recommended with maternal lithium use; however, if a woman chooses to breastfeed, the infant should be closely monitored for signs of lithium toxicity. Discontinue breastfeeding if a breastfed infant develops lithium toxicity. Clinical Considerations: Consider regular monitoring of lithium levels and thyroid function in a breastfed infant. 8.4 Pediatric Use The safety and effectiveness of lithium for monotherapy treatment of acute manic or mixed episodes of bipolar I disorder and maintenance monotherapy of bipolar I disorder in pediatric patients ages 7 to 17 years of age have been established in an acute-phase clinical trial of 8 weeks in duration followed by a 28-week randomized withdrawal phase [see Dosage and Administration (2.1) , Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , Clinical Studies (14) ] . The safety and effectiveness of lithium has not been established in pediatric patients less than 7 years of age with bipolar I disorder. 8.5 Geriatric Use Clinical studies of lithium carbonate tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in response between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, 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 treatment. Lithium is known to be substantially excreted by the kidneys, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. 8.6 Renal Impairment As lithium is eliminated primarily through the kidney, lithium renal clearance is decreased in patients with abnormal renal function, and the risk of lithium intoxication increases considerably in this setting. Lithium should not be used in severe renal insufficiency (creatinine clearance less than 30 mL/min evaluated by Cockcroft-Gault), especially if the condition requires adherence to a low-sodium diet [see Dosage and Administration (2.5) ] . Start patients with mild to moderately impaired renal function (creatinine clearance 30 to 89 mL/min evaluated by Cockcroft-Gault) with lower doses of lithium and titrate slowly while frequently monitoring serum lithium concentrations and for signs of lithium toxicity [see Dosage and Administration (2.5) ] .

8.1 Pregnancy Risk Summary: Lithium may cause harm when administered to a pregnant woman. Early voluntary reports to international birth registries suggested an increase in cardiovascular malformations, especially for Ebstein’s anomaly, with first trimester use of lithium. Subsequent case-control and cohort studies indicate that the increased risk for cardiac malformations is likely to be small; however, the data are insufficient to establish a drug-associated risk. There are concerns for maternal and/or neonatal lithium toxicity during late pregnancy and the postpartum period [see Clinical Considerations]. Published animal developmental and toxicity studies in mice and rats report an increased incidence of fetal mortality, decreased fetal weight, increased fetal skeletal abnormalities, and cleft palate (mouse fetuses only) with oral doses of lithium that produced serum concentrations similar to the human therapeutic range. Other published animal studies report adverse effects on embryonic implantation in rats after lithium administration. Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population(s) is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations: Dose Adjustments During Pregnancy and the Postpartum Period: If the decision is made to continue lithium treatment during pregnancy, serum lithium concentrations should be monitored and the dosage adjusted during pregnancy. Two to three days prior to delivery, lithium dosage should be decreased or discontinued to reduce the risk of maternal and/or neonatal toxicity. Lithium may be restarted in the post-partum period at preconception doses in medically stable patients as long as serum lithium levels are closely monitored [see Dosage and Administration (2.4) , Warnings and Precautions (5.1) ]. Fetal/Neonatal Adverse Reactions: Lithium toxicity may occur in neonates who were exposed to lithium in late pregnancy. A floppy baby syndrome including neurological, cardiac, and hepatic abnormalities that are similar to those seen with lithium toxicity in adults have been observed. Symptoms include hypotonia, respiratory distress syndrome, cyanosis, lethargy, feeding difficulties, depressed neonatal reflexes, neonatal depression, apnea, and bradycardia. Monitor neonates and provide supportive care until lithium is excreted and toxic signs disappear, which may take up to 14 days. Consider fetal echocardiography between 16 and 20 weeks gestation in a woman with first trimester lithium exposure because of the potential increased risk of cardiac malformations.

8.4 Pediatric Use The safety and effectiveness of lithium for monotherapy treatment of acute manic or mixed episodes of bipolar I disorder and maintenance monotherapy of bipolar I disorder in pediatric patients ages 7 to 17 years of age have been established in an acute-phase clinical trial of 8 weeks in duration followed by a 28-week randomized withdrawal phase [see Dosage and Administration (2.1) , Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , Clinical Studies (14) ] . The safety and effectiveness of lithium has not been established in pediatric patients less than 7 years of age with bipolar I disorder.

8.5 Geriatric Use Clinical studies of lithium carbonate tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in response between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, 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 treatment. Lithium is known to be substantially excreted by the kidneys, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

10 OVERDOSAGE The toxic concentrations for lithium (≥ 1.5 mEq/L) are close to the therapeutic concentrations [see Warnings and Precautions (5.1) ]. At lithium concentrations greater than 3 mEq/L, patients may progress to seizures, coma, and irreversible brain damage. Treatment: For current information on the management of poisoning or overdosage, contact the National Poison Control Center at 1-800-222-1222 or www.poison.org . No specific antidote for lithium poisoning is known. Mild symptoms of lithium toxicity can usually be treated by reduction in dose or cessation of the drug. In severe cases of lithium poisoning, the goal of treatment is elimination of this ion from the patient. Administration of gastric lavage should be performed, but use of activated charcoal is not recommended as it does not significantly absorb lithium ions. Hemodialysis is the treatment of choice as it is an effective and rapid means of removing lithium in patients with severe toxicity. As an alternative option, urea, mannitol and aminophylline can induce a significant increase in lithium excretion. Appropriate supportive care for the patient should be undertaken. Patients with impaired consciousness should have their airway protected and it is critical to correct any volume depletion or electrolyte imbalance. Patients should be monitored to prevent hypernatremia while receiving normal saline and careful regulation of kidney function is of utmost importance. Serum lithium concentrations should be closely monitored as there may be a rebound in serum lithium concentrations as a result of delayed diffusion from the body tissues. Likewise, during the late recovery phase, lithium should be re-administered with caution taking into account the possible release of significant lithium stores in body tissues.

11 DESCRIPTION Each capsule for oral administration contains lithium carbonate, USP 150 mg, 300 mg or 600 mg and the following inactive ingredients: colloidal silicon dioxide, gelatin, sodium lauryl sulfate, talc, titanium dioxide, FD&C Blue No. 1, FD&C Red No. 40, D&C Yellow No. 10, and the imprinting ink contains shellac, propylene glycol, potassium hydroxide, and black iron oxide. Lithium is an element of the alkali-metal group with atomic number 3, atomic weight 6.94, and an emission line at 671 nm on the flame photometer. Lithium Carbonate, USP is a white, crystalline powder with molecular formula Li 2 CO 3 and molecular weight 73.89.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The mechanism of action of lithium as a mood stabilizing agent is unknown. 12.3 Pharmacokinetics Absorption: After oral administration, lithium is reported to be completely absorbed in the upper gastrointestinal tract. Peak serum concentrations (T max ) occur 0.25 to 3 hours after oral administration of immediate release preparations and 2 to 6 hours after sustained-release preparations. Distribution: The distribution space of lithium approximates that of total body water, and the plasma protein binding is negligible. After equilibrium, the apparent volume of distribution is 0.7 to 1 L/kg. Metabolism: Lithium is not metabolized. Excretion: Lithium is primarily excreted in urine, proportionally to its serum concentration. Lithium is filtered by the glomerulus, and 80% is reabsorbed by passive diffusion in the proximal tubule. The elimination half-life of lithium is approximately 18 to 36 hours. Lithium excretion in feces is insignificant. Specific Populations: Pediatric Use: A pharmacokinetic study of lithium was performed in 39 subjects with bipolar I disorder. Both apparent clearance and apparent volume of distribution increase as body weight increases. A lower dose in patients < 30 kg is necessary to achieve lithium exposures in pediatric patients similar to those observed in adults treated at recommended doses of lithium [see Dosage and Administration (2.2) ] . The estimated plasma clearance was 0.59 L/h, 0.79 L/h and 1.17 L/h for pediatric patients weighing 20 kg, 30 kg and 50 kg, respectively.

12.3 Pharmacokinetics Absorption: After oral administration, lithium is reported to be completely absorbed in the upper gastrointestinal tract. Peak serum concentrations (T max ) occur 0.25 to 3 hours after oral administration of immediate release preparations and 2 to 6 hours after sustained-release preparations. Distribution: The distribution space of lithium approximates that of total body water, and the plasma protein binding is negligible. After equilibrium, the apparent volume of distribution is 0.7 to 1 L/kg. Metabolism: Lithium is not metabolized. Excretion: Lithium is primarily excreted in urine, proportionally to its serum concentration. Lithium is filtered by the glomerulus, and 80% is reabsorbed by passive diffusion in the proximal tubule. The elimination half-life of lithium is approximately 18 to 36 hours. Lithium excretion in feces is insignificant. Specific Populations: Pediatric Use: A pharmacokinetic study of lithium was performed in 39 subjects with bipolar I disorder. Both apparent clearance and apparent volume of distribution increase as body weight increases. A lower dose in patients < 30 kg is necessary to achieve lithium exposures in pediatric patients similar to those observed in adults treated at recommended doses of lithium [see Dosage and Administration (2.2) ] . The estimated plasma clearance was 0.59 L/h, 0.79 L/h and 1.17 L/h for pediatric patients weighing 20 kg, 30 kg and 50 kg, respectively.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis: There have been no long-term studies performed in animals to evaluate the carcinogenic potential of lithium. Mutagenesis: There have been no adequate studies conducted to evaluate the mutagenic and genotoxic potential of lithium. Impairment of Fertility: There have been no adequate studies performed in animals at current standards to evaluate the effect of lithium treatment on fertility. However, published studies in male mice and rats administered repeated daily dosing of lithium carbonate report adverse effects on male reproductive organs, decreased spermatogenesis and decreased testosterone levels.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis: There have been no long-term studies performed in animals to evaluate the carcinogenic potential of lithium. Mutagenesis: There have been no adequate studies conducted to evaluate the mutagenic and genotoxic potential of lithium. Impairment of Fertility: There have been no adequate studies performed in animals at current standards to evaluate the effect of lithium treatment on fertility. However, published studies in male mice and rats administered repeated daily dosing of lithium carbonate report adverse effects on male reproductive organs, decreased spermatogenesis and decreased testosterone levels.

14 CLINICAL STUDIES The safety and efficacy of lithium as a treatment for acute manic or mixed episodes of bipolar I disorder in pediatric patients (ages 7 to ≤18 years) was demonstrated in an 8-week, randomized, placebo-controlled, parallel group study (NCT01166425). In this study, 81 patients with a Young Mania Rating Scale (YMRS) score of 20 or more were randomized to receive lithium or placebo in a 2:1 ratio. Patients weighing more than 30 kg started lithium at 300 mg three times daily (900 mg/day) and could increase their dose by 300 mg every 3 days. Patients weighing 20 to 30 kg started lithium at 300 mg twice daily (600 mg/day) and could increase their dose by 300 mg weekly. No patients weighing less than 20 kg were enrolled. Lithium (mean serum level 0.98 ± 0.47 mEq/L) was statistically significantly superior to placebo in decreasing acute mania or mixed states as measured by the YMRS (see Table 5). In a 28-week randomized withdrawal analysis, 31 pediatric patients stabilized on lithium were assigned to either continue lithium or switch to placebo. The group receiving lithium demonstrated superiority to those receiving placebo in all-cause discontinuation (see Table 5). Table 5: Primary Efficacy Results Analysis Treatment Group Change From Baseline at Week 8 in YMRS Summary Score N Mean Baseline Score (SD) LS Mean Change from Baseline (SE) Difference Difference (drug minus placebo) in least-squares mean change from baseline. (95% CI) Acute Efficacy Lithium: 53 29.5 (5.6) -12.9 (3.1) -5.5 (-10.5, -0.5) Placebo: 28 30 (6) -7.3 (3.1) Analysis Treatment Group Patients analyzed by received treatment. All-cause Discontinuation N Number of Discontinued Subjects Hazard Ratio Lithium to placebo. (95% CI) Randomized Withdrawal Lithium: 17 7 (41.2%) 0.28 (0.10, 0.78) Placebo: 14 11 (78.6%) SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: confidence interval.

<table width="100%"><caption>Table 5: Primary Efficacy Results</caption><colgroup><col width="19%"/><col width="18%"/><col width="16%"/><col width="14%"/><col width="14%"/><col width="18%"/></colgroup><tbody><tr><td rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph>Analysis</paragraph></td><td align="center" rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph>Treatment Group</paragraph></td><td align="center" colspan="4" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph>Change From Baseline at Week 8 in YMRS Summary Score</paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>N</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Mean Baseline Score (SD)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>LS Mean Change from Baseline (SE)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Difference <footnote ID="_Ref162881371">Difference (drug minus placebo) in least-squares mean change from baseline.</footnote></paragraph><paragraph>(95% CI)</paragraph></td></tr><tr><td rowspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Acute Efficacy</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Lithium:</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>53</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>29.5 (5.6)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>-12.9 (3.1)</paragraph></td><td align="center" rowspan="2" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>-5.5 (-10.5, -0.5)</paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Placebo:</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>28</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>30 (6)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>-7.3 (3.1)</paragraph></td></tr><tr><td rowspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Analysis</paragraph></td><td align="center" rowspan="2" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Treatment Group <footnote ID="_Ref162881394">Patients analyzed by received treatment.</footnote></paragraph></td><td align="center" colspan="4" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>All-cause Discontinuation</paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>N</paragraph></td><td align="center" colspan="2" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Number of Discontinued Subjects</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Hazard Ratio <footnote ID="_Ref162881403">Lithium to placebo.</footnote></paragraph><paragraph>(95% CI)</paragraph></td></tr><tr><td rowspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Randomized Withdrawal</paragraph></td><td align="center" styleCode="Rrule Lr

e Botrule " valign="middle"><paragraph>Hazard Ratio <footnote ID="_Ref162881403">Lithium to placebo.</footnote></paragraph><paragraph>(95% CI)</paragraph></td></tr><tr><td rowspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Randomized Withdrawal</paragraph></td><td align="center" styleCode="Rrule Lr ule Toprule Botrule " valign="middle"><paragraph>Lithium:</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>17</paragraph></td><td align="center" colspan="2" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>7 (41.2%)</paragraph></td><td align="center" rowspan="2" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0.28 (0.10, 0.78)</paragraph></td></tr><tr><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph>Placebo:</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph>14</paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph>11 (78.6%)</paragraph></td></tr></tbody></table>

16 HOW SUPPLIED/STORAGE AND HANDLING Lithium Carbonate Capsules, USP 300 mg supplied as pink hard gelatin capsules imprinted with ‘300’ on the body and ‘G221’ on the cap, filled with white to off-white granules. Unit dose packages of 100 (10 x 10) NDC 60687-806-01 Storage and Dispense Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from moisture. FOR YOUR PROTECTION: Do not use if blister is torn or broken.

17 PATIENT COUNSELING INFORMATION Advise the patient to read FDA-approved patient labeling (Medication Guide) . Dosage and Administration: Advise patients that lithium is a mood stabilizer, and should only be taken as directed. Emphasize the importance of compliance with the prescribed treatment and to not adjust the dose of lithium without first consulting their healthcare provider. Inform patients that they will need to have regular blood draws to determine if their dose of lithium is appropriate. Instruct patients not to double the dose if a dose is missed, due to the complexity of individualized dosing and potential for lithium toxicity [see Dosage and Administration (2) , Warnings and Precautions (5.1) ]. Lithium Toxicity: Inform patients on adverse reactions related to lithium toxicity that require medical attention. Advise patients to discontinue lithium treatment and contact their healthcare provider if clinical signs of lithium toxicity such as diarrhea, vomiting, tremor, lack of muscle coordination, drowsiness, abnormal heart rhythm or muscular weakness occur [see Warnings and Precautions (5.1) ] . Lithium-Induced Polyuria: Counsel patients on the adverse reactions related to lithium-induced polyuria, when to seek medical attention, and the importance of maintaining normal diet with salt and staying hydrated [see Warnings and Precautions (5.2) ] . Hyponatremia: Counsel patients on the adverse reactions of hyponatremia, when to seek medical attention, the importance of maintaining a normal diet including adequate salt intake and staying hydrated [see Warnings and Precautions (5.3) ] . Salt supplements and additional fluids may be required if excessive losses occur. Serotonin Syndrome: Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of lithium with other serotonergic drugs including SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, tramadol, tryptophan, buspirone, 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) [see Warnings and Precautions (5.6) and Drug Interactions (7) ] . Drug Interactions: Advise patients that many drugs can interact with lithium and to inform their doctor and pharmacist if they are taking any over the counter medication, including herbal medication, or are started on a new prescription [see Drug Interactions (7) ] . Somnolence: Tell patients that lithium may cause somnolence particularly when initiating treatment and to be cautious about operating vehicles or hazardous machinery, until they are reasonably certain that lithium treatment does not affect them adversely [see Adverse Reactions (6) ] . Pregnancy: Advise pregnant women of the potential risk to a fetus and/or neonate [see Use in Specific Populations (8.1) ] . Lactation: Advise women that breastfeeding is not recommended during treatment with lithium [see Use in Specific Populations (8.2) ] . To order more Medication Guides call American Health Packaging at 1‐800‐707‐4621. For more information about the drug product, call 1 (888) 721-7115 or visit www.glenmarkpharma-us.com For more information about the packaging or labeling, call American Health Packaging at 1‐800‐707‐4621. Distributed by: American Health Packaging Columbus, OH 43217 8480601/1125

Medication Guide 8480601/1125 ​MEDICATION GUIDE Lithium (LITH-ee-əm) Carbonate capsules, USP What is the most important information I should know about lithium carbonate capsules? Lithium carbonate capsules can cause serious side effects, including: too much lithium in your blood (lithium toxicity). Lithium toxicity that can cause death may happen even if the lithium level in your blood is close to the right level for you. Your healthcare provider will need to monitor your blood levels of lithium to find the best dose for you. Take your lithium carbonate capsules exactly as your healthcare provider tells you to take it. Stop taking lithium carbonate capsules and call your healthcare provider right away if you have any symptoms of lithium toxicity including: o abnormal heartbeat o weak muscles o muscle twitching o vomiting o blurred vision o diarrhea o clumsiness o drowsiness o ringing in your ears Other symptoms may include: o lightheadedness o bloating o slurred speech o seizure o confusion o mood changes o breathing problems o coma What are lithium carbonate capsules? Lithium carbonate capsules are prescription medicines called mood-stabilizing agents used alone (monotherapy) for: the acute (short-term) treatment of people 7 years of age and older with manic and mixed episodes that happen with bipolar I disorder. maintenance treatment of bipolar I disorder in people 7 years of age and older. It is not known if lithium carbonate capsules are safe and effective in children under 7 years of age with bipolar I disorder. Who should not take lithium carbonate capsules? Do not take lithium carbonate capsules if you are allergic to lithium or any of the ingredients in lithium carbonate capsules. See the end of this Medication Guide for a complete list of ingredients in lithium carbonate capsules. What should I tell my healthcare provider before taking lithium carbonate capsules? Before taking lithium carbonate capsules, tell your healthcare provider if you: have kidney problems have heart problems have breathing problems have thyroid problems are pregnant or plan to become pregnant. Lithium carbonate may harm your unborn baby. are breastfeeding or plan to breastfeed. Lithium carbonate can pass into your breastmilk and may harm your baby. You should not breastfeed during treatment with lithium carbonate capsules. Talk to your healthcare provider about the best way to feed your baby if you take lithium carbonate capsules. Tell your healthcare provider about all the medicines you take, including prescription, over-the-counter medicines, vitamins, and herbal supplements. Using lithium carbonate capsules with certain other medicines may affect each other causing possible side effects. Lithium carbonate capsules may affect the way other medicines work, and other medicines may affect how lithium carbonate capsules works. Especially tell your healthcare provider if you take: MAOIs selective serotonin reuptake inhibitors (SSRIs) serotonin norepinephrine reuptake medicines used to treat migraine headaches inhibitors (SNRIs) called triptans tricyclic antidepressants fentanyl antipsychotic medicines tramadol tryptophan buspirone St John’s Wort Your healthcare provider can tell you if it is safe to take lithium carbonate capsules with your other medicines. Do not start or stop any medicines while taking lithium carbonate capsules without talking to your healthcare provider first. Know the medicines you take.

icines tramadol tryptophan buspirone St John’s Wort Your healthcare provider can tell you if it is safe to take lithium carbonate capsules with your other medicines. Do not start or stop any medicines while taking lithium carbonate capsules without talking to your healthcare provider first. Know the medicines you take. Keep a list of your medicines to show your healthcare provider and pharmacist when you get a new medicine. How should I take lithium carbonate capsules? Take your lithium carbonate capsules exactly as prescribed by your healthcare provider. Your healthcare provider will do certain blood tests before starting and during treatment with lithium carbonate capsules. Your healthcare provider may change your dose if needed. Do not change your dose on your own. Do not double your dose if a dose is missed. Talk with your healthcare provider if you miss a dose. Do not stop taking lithium carbonate capsules suddenly without talking to your healthcare provider. Your healthcare provider may change your lithium carbonate capsules dose to make sure you are taking the dose that is right for you. If you take too much lithium carbonate capsules, call your healthcare provider or poison control center, or go to the nearest hospital emergency room right away. In case of poisoning, call your poison control center at 1-800-222-1222. What should I avoid while taking lithium carbonate capsules? Do not drive, operate heavy machinery, or do other dangerous activities when you start taking lithium carbonate capsules, when your dose is changed, or until you know how lithium carbonate capsules affects you. Lithium carbonate capsules can make you sleepy. Talk to your healthcare provider about these activities. Avoid becoming overheated or dehydrated during exercise and in hot weather. Follow your healthcare provider instructions about the type and amount of liquids you should drink. In some cases, drinking too much liquid can be as unsafe as not drinking enough. Do not change the amount of salt in your diet. Changing the amount of salt in your diet could change the amount of lithium carbonate in your blood. What are the possible side effects of lithium carbonate capsules? See “What is the most important information I should know about lithium carbonate capsules? Lithium carbonate capsules may cause serious side effects, including: kidney problems. People who take lithium carbonate capsules may have to urinate often (polyuria) and have other kidney problems that may affect how their kidneys work. These problems can happen within a few weeks of starting to take lithium carbonate capsules or after taking lithium carbonate capsules for a long time. low levels of sodium (salt) in your blood (hyponatremia). Lithium carbonate capsules can cause you to lose sodium. Talk to your healthcare provider about your diet and how much fluid you are drinking when starting lithium carbonate capsules. If you have been sweating more than usual or have had diarrhea, you may need extra salt and more fluids. Talk to your healthcare provider if this happens. neurological problems. People who take lithium carbonate capsules with certain other medicines called antipsychotics may have symptoms such as weakness, tiredness, fever, tremors, and confusion. Talk to your healthcare provider if this happens. Ask if you are not sure about the medicines you take. serotonin syndrome. A potentially life-threatening problem called serotonin syndrome can happen when you take lithium carbonate capsules while you take certain medicines called serotonergic and MAOIs.

and confusion. Talk to your healthcare provider if this happens. Ask if you are not sure about the medicines you take. serotonin syndrome. A potentially life-threatening problem called serotonin syndrome can happen when you take lithium carbonate capsules while you take certain medicines called serotonergic and MAOIs. Symptoms of serotonin syndrome include: o agitation o coma o dizziness o fever o muscle twitching o nausea o seeing things that are not there o rapid pulse o sweating o tremors o become unstable o vomiting o confusion o high or low blood pressure o flushing o stiff muscles o seizures o diarrhea thyroid problems. high calcium levels in your blood (hypercalcemia) and changes in your parathyroid gland (hyperparathyroidism) that may not go away when you stop taking lithium carbonate capsules. heart problems. People who take lithium carbonate capsules may find out they also have a heart problem called Brugada Syndrome. People who have unexplained fainting or who have a family history of sudden unexplained death before 45 years of age may have Brugada Syndrome and not know it. If you faint or feel abnormal heartbeats, talk to your healthcare provider right away. increased pressure in the brain and swelling in the eye (pseudotumor cerebri) that can cause vision problems or blindness. If you have severe headaches behind your eyes, ringing in the ears, blurred vision, double vision, or brief periods of blindness, talk to your health care provider right away. The most common side effects of lithium carbonate capsules include: Adults with manic or mixed episodes of bipolar I disorder: o hand trembling o excessive urination o increased thirst o nausea o general discomfort when you start treatment Children 7 to 17 years of age with manic or mixed episodes of bipolar I disorder: o excessive urination o thyroid problems o hand trembling o excessive thirst o dizziness o rash o difficulty walking o decreased appetite o blurred vision o nausea o vomiting These are not all the possible side effects of lithium carbonate capsules. 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 lithium carbonate capsules? Store lithium carbonate capsules at room temperature, between 68°F to 77°F (20°C to 25°C). Keep capsules dry. Keep lithium carbonate capsules, and all medicines out of the reach of children. General information about the safe and effective use of lithium carbonate capsules. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use lithium carbonate capsules for a condition for which it was not prescribed. Do not give lithium carbonate capsules to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about lithium carbonate capsules that is written for healthcare professionals. For more information about lithium carbonate capsules, call Glenmark Pharmaceuticals Inc., USA at 1 (888) 721-7115. For more information about the packaging or labeling, call American Health Packaging at 1‐800‐707‐4621. What are the ingredients in lithium carbonate capsules? Active ingredient: lithium carbonate, USP Inactive ingredients: colloidal silicon dioxide, gelatin, sodium lauryl sulfate, talc, titanium dioxide, FD&C Blue No. 1, FD&C Red No. 40, D&C Yellow No. 10 and the imprinting ink contains shellac, propylene glycol, potassium hydroxide, and black iron oxide. To order more Medication Guides call American Health Packaging at 1‐800‐707‐4621. For more information about the drug product, call 1 (888) 721-7115 or visit www.glenmarkpharma-us.com For more information about the packaging or labeling, call American Health Packaging at 1‐800‐707‐4621.

hydroxide, and black iron oxide. To order more Medication Guides call American Health Packaging at 1‐800‐707‐4621. For more information about the drug product, call 1 (888) 721-7115 or visit www.glenmarkpharma-us.com For more information about the packaging or labeling, call American Health Packaging at 1‐800‐707‐4621. Distributed by: American Health Packaging Columbus, OH 43217 8480601/1125 This Medication Guide has been approved by the U.S. Food and Drug Administration.

WARNING Lithium toxicity is closely related to serum lithium levels, and can occur at doses close to therapeutic levels. Facilities for prompt and accurate serum lithium determinations should be available before initiating therapy (see DOSAGE AND ADMINISTRATION ).

DESCRIPTION Lithium Carbonate Extended-Release Tablets, USP contain lithium carbonate, USP a white crystalline powder with molecular formula Li 2 CO 3 and molecular weight 73.89. Lithium is an element of the alkali-metal group with atomic number 3, atomic weight 6.94, and an emission line at 671 nm on the flame photometer. Each light pink to pink colored circular, biconvex, coated, extended-release tablet contains 300 mg of lithium carbonate, USP. This slowly dissolving film-coated tablet is designed to give lower serum lithium peak concentrations than obtained with conventional oral lithium dosage forms. Inactive ingredients consist of sodium chloride, povidone, sorbitol, sodium starch glycolate, sodium lauryl sulfate, calcium stearate, hypromellose, titanium dioxide, polyethylene glycol and iron oxide red. Product meets USP Dissolution Test 1.

ACTIONS Preclinical studies have shown that lithium alters sodium transport in nerve and muscle cells and effects a shift toward intraneuronal metabolism of catecholamines, but the specific biochemical mechanism of lithium action in mania is unknown.

INDICATIONS Lithium carbonate extended-release tablets are indicated in the treatment of manic episodes of Bipolar Disorder. Bipolar Disorder, Manic (DSM-IV) is equivalent to Manic Depressive illness, Manic, in the older DSM-II terminology. Lithium carbonate extended-release tablets are also indicated as a maintenance treatment for individuals with a diagnosis of Bipolar Disorder. Maintenance therapy reduces the frequency of manic episodes and diminishes the intensity of those episodes which may occur. Typical symptoms of mania include pressure of speech, motor hyperactivity, reduced need for sleep, flight of ideas, grandiosity, elation, poor judgment, aggressiveness, and possibly hostility. When given to a patient experiencing a manic episode, lithium may produce a normalization of symptomatology within 1 to 3 weeks.

WARNINGS Lithium Toxicity The toxic concentrations for lithium (≥1.5 mEq/L) are close to the therapeutic range (0.8 to 1.2 mEq/L). Some patients abnormally sensitive to lithium may exhibit toxic signs at serum concentrations that are considered within the therapeutic range (see BOXED WARNING and DOSAGE AND ADMINISTRATION ). Lithium may take up to 24 hours to distribute into brain tissue, so occurrence of acute toxicity symptoms may be delayed. Neurological signs of lithium toxicity range from mild neurological adverse reactions such as fine tremor, lightheadedness, lack of coordination, and weakness; to moderate manifestations like giddiness, apathy, drowsiness, hyperreflexia, muscle twitching, ataxia, blurred vision, tinnitus, and slurred speech; and severe manifestations such as clonus, confusion, seizure, coma, and death. In rare cases, neurological sequelae may persist despite discontinuing lithium treatment and may be associated with cerebellar atrophy. Cardiac manifestations involve electrocardiographic changes, such as prolonged QT interval, ST and T-wave changes and myocarditis. Renal manifestations include urine concentrating defect, nephrogenic diabetes insipidus, and renal failure. Respiratory manifestations include dyspnea, aspiration pneumonia, and respiratory failure. Gastrointestinal manifestations include nausea, vomiting, diarrhea, and bloating. No specific antidote for lithium poisoning is known (see OVERDOSAGE ). The risk of lithium toxicity is increased by: Recent onset of concurrent febrile illness Concomitant administration of drugs which increase lithium serum concentrations by pharmacokinetic interactions or drugs affecting kidney function (see PRECAUTIONS-Drug Interactions ) Acute ingestion Impaired renal function Volume depletion or dehydration Significant cardiovascular disease Changes in electrolyte concentrations (especially sodium and potassium) Monitor for signs and symptoms of lithium toxicity. If symptoms occur, decrease dosage or discontinue lithium treatment. Unmasking of Brugada Syndrome There have been postmarketing reports of a possible association between treatment with lithium and the unmasking of Brugada Syndrome. Brugada Syndrome is a disorder characterized by abnormal electrocardiographic (ECG) findings and a risk of sudden death. Lithium should generally be avoided in patients with Brugada Syndrome or those suspected of having Brugada Syndrome. Consultation with a cardiologist is recommended if: (1) treatment with lithium is under consideration for patients suspected of having Brugada Syndrome or patients who have risk factors for Brugada Syndrome, e.g., unexplained syncope, a family history of Brugada Syndrome, or a family history of sudden unexplained death before the age of 45 years, (2) patients who develop unexplained syncope or palpitations after starting lithium therapy. Psuedotumor Cerebri Cases of pseudotumor cerebri (increased intracranial pressure and papilledema) have been reported with lithium use. If undetected, this condition may result in enlargement of the blind spot, constriction of visual fields, and eventual blindness due to optic atrophy. Lithium should be discontinued, if clinically possible, if this syndrome occurs. Renal Effects Chronic lithium therapy may be associated with diminution of renal concentrating ability, occasionally presenting as nephrogenic diabetes insipidus, with polyuria and polydipsia.

, and eventual blindness due to optic atrophy. Lithium should be discontinued, if clinically possible, if this syndrome occurs. Renal Effects Chronic lithium therapy may be associated with diminution of renal concentrating ability, occasionally presenting as nephrogenic diabetes insipidus, with polyuria and polydipsia. Such patients should be carefully managed to avoid dehydration with resulting lithium retention and toxicity. This condition is usually reversible when lithium is discontinued. Post marketing cases consistent with nephrotic syndrome have been reported with the use of lithium. Biopsy findings in patients with nephrotic syndrome include minimal change disease and focal segmental glomerulosclerosis. Discontinuation of lithium in patients with nephrotic syndrome has resulted in remission of nephrotic syndrome. Morphologic changes with glomerular and interstitial fibrosis and nephron atrophy have been reported in patients on chronic lithium therapy. Morphologic changes have also been seen in manic-depressive patients never exposed to lithium. The relationship between renal function and morphologic changes and their association with lithium therapy have not been established. Kidney function should be assessed prior to and during lithium therapy. Routine urinalysis and other tests may be used to evaluate tubular function (e.g., urine specific gravity or osmolality following a period of water deprivation, or 24-hour urine volume) and glomerular function (e.g., serum creatinine, creatinine clearance, or proteinuria). During lithium therapy, progressive or sudden changes in renal function, even within the normal range, indicate the need for re-evaluation of treatment. Encephalopathic Syndrome An encephalopathic syndrome (characterized by weakness, lethargy, fever, tremulousness and confusion, extrapyramidal symptoms, leukocytosis, elevated serum enzymes, BUN, and FBS) has occurred in a few patients treated with lithium plus a neuroleptic, most notably haloperidol. In some instances, the syndrome was followed by irreversible brain damage. Because of possible causal relationship between these events and the concomitant administration of lithium and neuroleptic drugs, patients receiving such combined therapy or patients with organic brain syndrome or other CNS impairment should be monitored closely for early evidence of neurologic toxicity and treatment discontinued promptly if such signs appear. This encephalopathic syndrome may be similar to or the same as Neuroleptic Malignant Syndrome (NMS). Serotonin Syndrome Lithium can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, triptans, tricyclic antidepressants, fentanyl, tramadol, tryptophan, buspirone, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs (see PRECAUTIONS ). 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). Monitor all patients taking lithium for the emergence of serotonin syndrome. Discontinue treatment with lithium and any concomitant serotonergic agents immediately if the above symptoms occur and initiate supportive symptomatic treatment.

ion), seizures, and gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Monitor all patients taking lithium for the emergence of serotonin syndrome. Discontinue treatment with lithium and any concomitant serotonergic agents immediately if the above symptoms occur and initiate supportive symptomatic treatment. If concomitant use of lithium with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms. Concomitant Use with Neuromuscular Blocking Agents Lithium may prolong the effects of neuromuscular blocking agents. Therefore, neuromuscular blocking agents should be given with caution to patients receiving lithium. Usage in Pregnancy Adverse effects on nidation in rats, embryo viability in mice, and metabolism in vitro of rat testis and human spermatozoa have been attributed to lithium, as have teratogenicity in submammalian species and cleft palate in mice. In humans, lithium may cause fetal harm when administered to a pregnant woman. Data from lithium birth registries suggest an increase in cardiac and other anomalies, especially Ebstein’s anomaly. If this drug is used in women of childbearing potential, or during pregnancy, or if a patient becomes pregnant while taking this drug, the patient should be apprised by their physician of the potential hazard to the fetus. Usage in Nursing Mothers Lithium is excreted in human milk. Nursing should not be undertaken during lithium therapy except in rare and unusual circumstances where, in the view of the physician, the potential benefits to the mother outweigh possible hazard to the infant or neonate. Signs and symptoms of lithium toxicity such as hypertonia, hypothermia, cyanosis, and ECG changes have been reported in some infants and neonates. Pediatric Use Safety and effectiveness in pediatric patients under 12 years of age have not been determined; its use in these patients is not recommended. There has been a report of transient syndrome of acute dystonia and hyperreflexia occurring in a 15 kg pediatric patient who ingested 300 mg of lithium carbonate.

PRECAUTIONS The ability to tolerate lithium is greater during the acute manic phase and decreases when manic symptoms subside (see DOSAGE AND ADMINISTRATION ). The distribution space of lithium approximates that of total body water. Lithium is primarily excreted in urine with insignificant excretion in feces. Renal excretion of lithium is proportional to its plasma concentration. The elimination half-life of lithium is approximately 24 hours. Lithium decreases sodium reabsorption by the renal tubules which could lead to sodium depletion. Therefore, it is essential for the patient to maintain a normal diet, including salt, and an adequate fluid intake (2500 to 3500 mL) at least during the initial stabilization period. Decreased tolerance to lithium has been reported to ensue from protracted sweating or diarrhea and, if such occur, supplemental fluid and salt should be administered under careful medical supervision and lithium intake reduced or suspended until the condition is resolved. In addition to sweating and diarrhea, concomitant infection with elevated temperatures may also necessitate a temporary reduction or cessation of medication. Previously existing thyroid disorders do not necessarily constitute a contraindication to lithium treatment. Where hypothyroidism preexists, careful monitoring of thyroid function during lithium stabilization and maintenance allows for correction of changing thyroid parameters and/or adjustment of lithium doses, if any. If hypothyroidism occurs during lithium stabilization and maintenance, supplemental thyroid treatment may be used. Drug Interactions Diuretic-, ACE-, and ARB-induced sodium loss may increase serum lithium concentrations. Start with lower doses of lithium or reduce dosage, while frequently monitoring serum lithium concentrations and signs of lithium toxicity. See WARNINGS for additional caution information. Concomitant administration of lithium with serotonergic drugs can precipitate serotonin syndrome. Monitor patients for signs and symptoms of serotonin syndrome, particularly during lithium initiation. If serotonin syndrome occurs, consider discontinuation of lithium and/or concomitant serotonergic drugs. Examples of serotonergic drugs include selective serotonin reuptake inhibitors (SSRI), serotonin and norepinephrine reuptake inhibitors (SNRI), and monoamine oxidase inhibitors (MAOI). Concomitant administration of methyldopa, phenytoin, or carbamazepine with lithium may increase the risk of adverse reactions with these drugs. The following drugs can lower serum lithium concentrations by increasing urinary lithium excretion: acetazolamide, urea, xanthine preparations, and alkalinizing agents such as sodium bicarbonate. Concomitant extended use of iodide preparations, especially potassium iodide, with lithium may produce hypothyroidism. Concurrent use of calcium channel blocking agents with lithium may increase the risk of neurotoxicity in the form of ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus. Concurrent use of metronidazole with lithium may provoke lithium toxicity due to reduced renal clearance. Patients receiving such combined therapy should be monitored closely. Concurrent use of fluoxetine with lithium has resulted in both increased and decreased serum lithium concentrations. Patients receiving such combined therapy should be monitored closely.

um may provoke lithium toxicity due to reduced renal clearance. Patients receiving such combined therapy should be monitored closely. Concurrent use of fluoxetine with lithium has resulted in both increased and decreased serum lithium concentrations. Patients receiving such combined therapy should be monitored closely. Nonsteroidal anti-inflammatory drugs (NSAIDs): Lithium levels should be closely monitored when patients initiate or discontinue NSAID use. In some cases, lithium toxicity has resulted from interactions between a NSAID and lithium. Indomethacin and piroxicam have been reported to increase significantly steady-state plasma lithium concentrations. There is also evidence that other nonsteroidal anti‑inflammatory agents, including the selective cyclooxygenase-2 (COX-2) inhibitors, have the same effect. In a study conducted in healthy subjects, mean steady-state lithium plasma levels increased approximately 17% in subjects receiving lithium 450 mg BID with celecoxib 200 mg BID as compared to subjects receiving lithium alone. Concomitant use of lithium with a Sodium-Glucose Cotransporter 2 (SGLT2) inhibitor may decrease serum lithium concentrations. Monitor serum lithium concentration more frequently during SGLT2 inhibitor initiation and dosage changes. Lithium may impair mental and/or physical abilities. Patients should be cautioned about activities requiring alertness (e.g., operating vehicles or machinery). Usage in Pregnancy See WARNINGS . Usage in Nursing Mothers Because of the potential for serious adverse reactions in nursing infants and neonates from lithium, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother (see WARNINGS ). Pediatric Use Safety and effectiveness in pediatric patients below the age of 12 have not been established (see WARNINGS ). Geriatric Use Clinical studies of lithium carbonate extended-release tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, 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 therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Usage in Nursing Mothers Because of the potential for serious adverse reactions in nursing infants and neonates from lithium, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother (see WARNINGS ).

Geriatric Use Clinical studies of lithium carbonate extended-release tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, 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 therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

ADVERSE REACTIONS The occurrence and severity of adverse reactions are generally directly related to serum lithium concentrations and to individual patient sensitivity to lithium. They generally occur more frequently and with greater severity at higher concentrations. Adverse reactions may be encountered at serum lithium concentrations below 1.5 mEq/L. Mild to moderate adverse reactions may occur at concentrations from 1.5 to 2.5 mEq/L, and moderate to severe reactions may be seen at concentrations from 2 mEq/L and above. Fine hand tremor, polyuria, and mild thirst may occur during initial therapy for the acute manic phase and may persist throughout treatment. Transient and mild nausea and general discomfort may also appear during the first few days of lithium administration. These side effects usually subside with continued treatment or with a temporary reduction or cessation of dosage. If persistent, a cessation of lithium therapy may be required. Diarrhea, vomiting, drowsiness, muscular weakness, and lack of coordination may be early signs of lithium intoxication, and can occur at lithium concentrations below 2 mEq/L. At higher concentrations, giddiness, ataxia, blurred vision, tinnitus, and a large output of dilute urine may be seen. Serum lithium concentrations above 3 mEq/L may produce a complex clinical picture involving multiple organs and organ systems. Serum lithium concentrations should not be permitted to exceed 2 mEq/L during the acute treatment phase. The following reactions have been reported and appear to be related to serum lithium concentrations, including concentrations within the therapeutic range: Central Nervous System: tremor, muscle hyperirritability (fasciculations, twitching, clonic movements of whole limbs), hypertonicity, ataxia, choreoathetotic movements, hyperactive deep tendon reflex, extrapyramidal symptoms including acute dystonia, cogwheel rigidity, blackout spells, epileptiform seizures, slurred speech, dizziness, vertigo, downbeat nystagmus, incontinence of urine or feces, somnolence, psychomotor retardation, restlessness, confusion, stupor, coma, tongue movements, tics, tinnitus, hallucinations, poor memory, slowed intellectual functioning, startled response, worsening of organic brain syndromes. Cardiovascular: cardiac arrhythmia, hypotension, peripheral circulatory collapse, bradycardia, sinus node dysfunction with severe bradycardia (which may result in syncope), Unmasking of Brugada Syndrome (See WARNINGS and PATIENT COUNSELING INFORMATION ). Gastrointestinal: anorexia, nausea, vomiting, diarrhea, gastritis, salivary gland swelling, abdominal pain, excessive salivation, flatulence, indigestion. Genitourinary: glycosuria, decreased creatinine clearance, albuminuria, oliguria, and symptoms of nephrogenic diabetes insipidus including polyuria, thirst and polydipsia. Dermatologic: drying and thinning of hair, alopecia, anesthesia of skin, acne, chronic folliculitis, xerosis cutis, psoriasis or its exacerbation, generalized pruritus with or without rash, cutaneous ulcers, angioedema, drug reaction with eosinophilia and systemic symptoms (DRESS). Autonomic Nervous System: blurred vision, dry mouth, impotence/sexual dysfunction. Thyroid Abnormalities: euthyroid goiter and/or hypothyroidism (including myxedema) accompanied by lower T3 and T4. 131 Iodine uptake may be elevated (see PRECAUTIONS ). Paradoxically, rare cases of hyperthyroidism have been reported.

S). Autonomic Nervous System: blurred vision, dry mouth, impotence/sexual dysfunction. Thyroid Abnormalities: euthyroid goiter and/or hypothyroidism (including myxedema) accompanied by lower T3 and T4. 131 Iodine uptake may be elevated (see PRECAUTIONS ). Paradoxically, rare cases of hyperthyroidism have been reported. EEG Changes: diffuse slowing, widening of frequency spectrum, potentiation and disorganization of background rhythm. EKG Changes: reversible flattening, isoelectricity or inversion of T-waves. Miscellaneous: fatigue, lethargy, transient scotomata, exophthalmos, dehydration, weight loss, leucocytosis, headache, transient hyperglycemia, hypercalcemia, hyperparathyroidism, albuminuria, excessive weight gain, edematous swelling of ankles or wrists, metallic taste, dysgeusia/taste distortion, salty taste, thirst, swollen lips, tightness in chest, swollen and/or painful joints, fever, polyarthralgia, and dental caries. Some reports of nephrogenic diabetes insipidus, hyperparathyroidism, and hypothyroidism which persist after lithium discontinuation have been received. A few reports have been received of the development of painful discoloration of fingers and toes and coldness of the extremities within one day of starting lithium treatment. The mechanism through which these symptoms (resembling Raynaud’s Syndrome) developed is not known. Recovery followed discontinuance.

DOSAGE AND ADMINISTRATION Acute Mania Optimal patient response can usually be established with 1800 mg/day in the following dosages: ACUTE MANIA Morning Afternoon Nighttime Lithium Carbonate Extended-Release Tablets 1 3 tablets (900 mg) 3 tablets (900 mg) 1 Can also be administered on 600 mg TID recommended dosing interval. Such doses will normally produce an effective serum lithium concentration ranging between 1 and 1.5 mEq/L. Dosage must be individualized according to serum concentrations and clinical response. Regular monitoring of the patient’s clinical state and of serum lithium concentrations is necessary. Serum concentrations should be determined twice per week during the acute phase, and until the serum concentrations and clinical condition of the patient have been stabilized. Long-Term Control Desirable serum lithium concentrations are 0.6 to 1.2 mEq/L which can usually be achieved with 900 to 1200 mg/day. Dosage will vary from one individual to another, but generally the following dosages will maintain this concentration: LONG-TERM CONTROL Morning Afternoon Nighttime Lithium Carbonate Extended-Release Tablets 1 2 tablets (600 mg) 2 tablets (600 mg) ¹Can be administered on TID recommended dosing interval up to 1200 mg/day. Serum lithium concentrations in uncomplicated cases receiving maintenance therapy during remission should be monitored at least every two months. Patients abnormally sensitive to lithium may exhibit toxic signs at serum concentrations of 1 to 1.5 mEq/L. Geriatric patients often respond to reduced dosage, and may exhibit signs of toxicity at serum concentrations ordinarily tolerated by other patients. In general, dose selection for an elderly patient should be cautious, 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. Important Considerations Blood samples for serum lithium determinations should be drawn immediately prior to the next dose when lithium concentrations are relatively stable (i.e., 8 to 12 hours after previous dose). Total reliance must not be placed on serum concentrations alone. Accurate patient evaluation requires both clinical and laboratory analysis. Lithium Carbonate extended-release tablets must be swallowed whole and never chewed or crushed.

OVERDOSAGE The toxic concentrations for lithium (≥ 1.5 mEq/L) are close to the therapeutic concentrations. It is therefore important that patients and their families be cautioned to watch for early toxic symptoms and to discontinue the drug and inform the physician should they occur (see WARNINGS: Lithium Toxicity ). Treatment No specific antidote for lithium poisoning is known. Treatment is supportive. Early symptoms of lithium toxicity can usually be treated by reduction or cessation of dosage of the drug and resumption of the treatment at a lower dose after 24 to 48 hours. In severe cases of lithium poisoning, the first and foremost goal of treatment consists of elimination of this ion from the patient. Treatment is essentially the same as that used in barbiturate poisoning: 1) gastric lavage, 2) correction of fluid and electrolyte imbalance and, 3) regulation of kidney functioning. Urea, mannitol, and aminophylline all produce significant increases in lithium excretion. Hemodialysis is an effective and rapid means of removing the ion from the severely toxic patient. However, patient recovery may be slow. Infection prophylaxis, regular chest X-rays, and preservation of adequate respiration are essential.

PATIENT COUNSELING INFORMATION Information for Patients: A condition known as Brugada Syndrome may pre-exist and be unmasked by lithium therapy. Brugada Syndrome is a heart disorder characterized by abnormal electrocardiographic (ECG) findings and risk of sudden death. Patients should be advised to seek immediate emergency assistance if they experience fainting, light-headedness, abnormal heart beats, or shortness of breath because they may have a potentially life-threatening heart disorder known as Brugada Syndrome. Repackaged By / Distributed By: RemedyRepack Inc. 625 Kolter Drive, Indiana, PA 15701 (724) 465-8762

HOW SUPPLIED Lithium Carbonate Extended-Release Tablets, USP 300 mg, are supplied as light pink to pink colored circular, biconvex, coated tablets debossed with ‘223’ on one side and plain on the other side. NDC: 70518-3875-00 PACKAGING: 30 in 1 BLISTER PACK Storage Conditions Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30° C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from moisture and store in a dry place. Keep tablets in original/pharmacy container. Dispense in a tight, child-resistant container (USP). Repackaged and Distributed By: Remedy Repack, Inc. 625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762

Rx only WARNING Lithium toxicity is closely related to serum lithium levels, and can occur at doses close to therapeutic levels. Facilities for prompt and accurate serum lithium determinations should be available before initiating therapy [see DOSAGE AND ADMINISTRATION ].

WARNING Lithium toxicity is closely related to serum lithium levels, and can occur at doses close to therapeutic levels. Facilities for prompt and accurate serum lithium determinations should be available before initiating therapy [see DOSAGE AND ADMINISTRATION ].

DESCRIPTION Lithium Carbonate Extended-Release Tablets USP, contain lithium carbonate USP, a white, crystalline powder with molecular formula Li 2 CO 3 and molecular weight 73.89 g/mol. Lithium is an element of the alkali‑metal group with atomic number 3, atomic weight 6.94 and an emission line at 671 nm on the flame photometer. Lithium Carbonate Extended-Release Tablets USP Each off-white to pale yellow, circular, beveled edged, biconvex uncoated tablets with ‘224’ debossed on one side, ‘G’ and a break line debossed on the other side, contains lithium carbonate, 450 mg. Inactive ingredients consist of ferric oxide yellow, hypromellose, magnesium stearate, microcrystalline cellulose, sodium alginate, sodium starch glycolate and talc. Product meets USP Dissolution Test 2. Lithium Carbonate Extended-Release Tablets USP, 450 mg are designed to release a portion of the dose initially and the remainder gradually; the release pattern of the controlled release tablets reduces the variability in lithium blood levels seen with the immediate release dosage forms.

CLINICAL PHARMACOLOGY Preclinical studies have shown that lithium alters sodium transport in nerve and muscle cells and effects a shift toward intraneuronal metabolism of catecholamines, but the specific biochemical mechanism of lithium action in mania is unknown.

INDICATIONS AND USAGE Lithium Carbonate Extended-Release Tablets are indicated in the treatment of manic episodes of manic-depressive illness. Maintenance therapy prevents or diminishes the intensity of subsequent episodes in those manic-depressive patients with a history of mania. Typical symptoms of mania include pressure of speech, motor hyperactivity, reduced need for sleep, flight of ideas, grandiosity, elation, poor judgment, aggressiveness and possibly hostility. When given to a patient experiencing a manic episode, Lithium Carbonate Extended-Release Tablets may produce a normalization of symptomatology within 1 to 3 weeks.

WARNINGS Lithium Toxicity The toxic concentrations for lithium (≥1.5 mEq/L) are close to the therapeutic range (0.8 to 1.2 mEq/L). Some patients abnormally sensitive to lithium may exhibit toxic signs at serum concentrations that are considered within the therapeutic range [see BOXED WARNING , DOSAGE AND ADMINISTRATION ]. Lithium may take up to 24 hours to distribute into brain tissue, so occurrence of acute toxicity symptoms may be delayed. Neurological signs of lithium toxicity range from mild neurological adverse reactions such as fine tremor, lightheadedness, lack of coordination, and weakness; to moderate manifestations like giddiness, apathy, drowsiness, hyperreflexia, muscle twitching, ataxia, blurred vision, tinnitus, and slurred speech; and severe manifestations such as clonus, confusion, seizure, coma, and death. In rare cases, neurological sequelae may persist despite discontinuing lithium treatment and may be associated with cerebellar atrophy. Cardiac manifestations involve electrocardiographic changes, such as prolonged QT interval, ST and T-wave changes and myocarditis. Renal manifestations include urine concentrating defect, nephrogenic diabetes insipidus, and renal failure. Respiratory manifestations include dyspnea, aspiration pneumonia, and respiratory failure. Gastrointestinal manifestations include nausea, vomiting, diarrhea, and bloating. No specific antidote for lithium poisoning is known [see OVERDOSAGE ]. The risk of lithium toxicity is increased by: Recent onset of concurrent febrile illness Concomitant administration of drugs which increase lithium serum concentrations by pharmacokinetic interactions or drugs affecting kidney function [see PRECAUTIONS-DRUG INTERACTIONS ] Acute ingestion Impaired renal function Volume depletion or dehydration Significant cardiovascular disease Changes in electrolyte concentrations (especially sodium and potassium) Monitor for signs and symptoms of lithium toxicity. If symptoms occur, decrease dosage or discontinue lithium treatment. Unmasking of Brugada Syndrome There have been postmarketing reports of a possible association between treatment with lithium and the unmasking of Brugada Syndrome. Brugada Syndrome is a disorder characterized by abnormal electrocardiographic (ECG) findings and a risk of sudden death. Lithium should generally be avoided in patients with Brugada Syndrome or those suspected of having Brugada Syndrome. Consultation with a cardiologist is recommended if: (1) treatment with lithium is under consideration for patients suspected of having Brugada Syndrome or patients who have risk factors for Brugada Syndrome, e.g., unexplained syncope, a family history of Brugada Syndrome, or a family history of sudden unexplained death before the age of 45 years, (2) patients who develop unexplained syncope or palpitations after starting lithium therapy. Pseudotumor Cerebri Cases of pseudotumor cerebri (increased intracranial pressure and papilledema) have been reported with lithium use. If undetected, this condition may result in enlargement of the blind spot, constriction of visual fields, and eventual blindness due to optic atrophy. Lithium should be discontinued, if clinically possible, if this syndrome occurs. Renal Effects Chronic lithium therapy may be associated with diminution of renal concentrating ability, occasionally presenting as nephrogenic diabetes insipidus, with polyuria and polydipsia.

, and eventual blindness due to optic atrophy. Lithium should be discontinued, if clinically possible, if this syndrome occurs. Renal Effects Chronic lithium therapy may be associated with diminution of renal concentrating ability, occasionally presenting as nephrogenic diabetes insipidus, with polyuria and polydipsia. Such patients should be carefully managed to avoid dehydration with resulting lithium retention and toxicity. This condition is usually reversible when lithium is discontinued. Post marketing cases consistent with nephrotic syndrome have been reported with the use of lithium. Biopsy findings in patients with nephrotic syndrome include minimal change disease and focal segmental glomerulosclerosis. Discontinuation of lithium in patients with nephrotic syndrome has resulted in remission of nephrotic syndrome. Morphologic changes with glomerular and interstitial fibrosis and nephron atrophy have been reported in patients on chronic lithium therapy. Morphologic changes have also been seen in manic-depressive patients never exposed to lithium. The relationship between renal functional and morphologic changes and their association with lithium therapy have not been established. Kidney function should be assessed prior to and during lithium therapy. Routine urinalysis and other tests may be used to evaluate tubular function (e.g., urine specific gravity or osmolality following a period of water deprivation, or 24-hour urine volume) and glomerular function (e.g., serum creatinine, creatinine clearance or proteinuria). During lithium therapy, progressive or sudden changes in renal function, even within the normal range, indicate the need for reevaluation of treatment. Encephalopathic Syndrome An encephalopathic syndrome (characterized by weakness, lethargy, fever, tremulousness and confusion, extrapyramidal symptoms, leukocytosis, elevated serum enzymes, BUN and FBS) has occurred in a few patients treated with lithium plus a neuroleptic. In some instances, the syndrome was followed by irreversible brain damage. Because of a possible causal relationship between these events and the concomitant administration of lithium and neuroleptics, patients receiving such combined therapy should be monitored closely for early evidence of neurologic toxicity and treatment discontinued promptly if such signs appear. This encephalopathic syndrome may be similar to or the same as neuroleptic malignant syndrome (NMS). Serotonin Syndrome Lithium can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, triptans, tricyclic antidepressants, fentanyl, tramadol, tryptophan, buspirone, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [see PRECAUTIONS ]. 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). Monitor all patients taking lithium for the emergence of serotonin syndrome. Discontinue treatment with lithium and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of lithium with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.

eatment with lithium and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of lithium with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms. Concomitant Use with Neuromuscular Blocking Agents Lithium may prolong the effects of neuromuscular blocking agents. Therefore, neuromuscular blocking agents should be given with caution to patients receiving lithium. Usage in Pregnancy Adverse effects on implantation in rats, embryo viability in mice and metabolism in vitro of rat testes and human spermatozoa have been attributed to lithium, as have teratogenicity in submammalian species and cleft palates in mice. In humans, lithium carbonate may cause fetal harm when administered to a pregnant woman. Data from lithium birth registries suggest an increase in cardiac and other anomalies, especially Ebstein’s anomaly. If this drug is used in women of childbearing potential, or during pregnancy, or if a patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Usage in Nursing Mothers Lithium is excreted in human milk. Nursing should not be undertaken during lithium therapy except in rare and unusual circumstances where, in the view of the physician, the potential benefits to the mother outweigh possible hazards to the infant or neonate. Signs and symptoms of lithium toxicity such as hypertonia, hypothermia, cyanosis, and ECG changes have been reported in some infants and neonates. Usage in Pediatric Patients Safety and effectiveness in pediatric patients under 12 years of age have not been determined; its use in these patients is not recommended. There has been a report of a transient syndrome of acute dystonia and hyperreflexia occurring in a 15 kg child who ingested 300 mg of lithium carbonate.

Usage in Pregnancy Adverse effects on implantation in rats, embryo viability in mice and metabolism in vitro of rat testes and human spermatozoa have been attributed to lithium, as have teratogenicity in submammalian species and cleft palates in mice. In humans, lithium carbonate may cause fetal harm when administered to a pregnant woman. Data from lithium birth registries suggest an increase in cardiac and other anomalies, especially Ebstein’s anomaly. If this drug is used in women of childbearing potential, or during pregnancy, or if a patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Usage in Nursing Mothers Lithium is excreted in human milk. Nursing should not be undertaken during lithium therapy except in rare and unusual circumstances where, in the view of the physician, the potential benefits to the mother outweigh possible hazards to the infant or neonate. Signs and symptoms of lithium toxicity such as hypertonia, hypothermia, cyanosis, and ECG changes have been reported in some infants and neonates. Usage in Nursing Mothers Because of the potential for serious adverse reactions in nursing infants and neonates from lithium, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother [see WARNINGS ].

Usage in Pediatric Patients Safety and effectiveness in pediatric patients under 12 years of age have not been determined; its use in these patients is not recommended. There has been a report of a transient syndrome of acute dystonia and hyperreflexia occurring in a 15 kg child who ingested 300 mg of lithium carbonate. Pediatric Use Safety and effectiveness in pediatric patients below the age of 12 have not been established [see WARNINGS ].

PRECAUTIONS General The ability to tolerate lithium is greater during the acute manic phase and decreases when manic symptoms subside [see DOSAGE AND ADMINISTRATION ]. The distribution space of lithium approximates that of total body water. Lithium is primarily excreted in urine with insignificant excretion in feces. Renal excretion of lithium is proportional to its plasma concentration. The half-life of elimination of lithium is approximately 24 hours. Lithium decreases sodium reabsorption by the renal tubules which could lead to sodium depletion. Therefore, it is essential for the patient to maintain a normal diet, including salt, and an adequate fluid intake (2,500 to 3,000 mL) at least during the initial stabilization period. Decreased tolerance to lithium has been reported to ensue from protracted sweating or diarrhea and, if such occur, supplemental fluid and salt should be administered under careful medical supervision and lithium intake reduced or suspended until the condition is resolved. In addition to sweating and diarrhea, concomitant infection with elevated temperatures may also necessitate a temporary reduction or cessation of medication. Previously existing underlying thyroid disorders do not necessarily constitute a contraindication to lithium treatment; where hypothyroidism preexists, careful monitoring of thyroid function during lithium stabilization and maintenance allows for correction of changing thyroid parameters, if any; where hypothyroidism occurs during lithium stabilization and maintenance, supplemental thyroid treatment may be used. Information for Patients Lithium carbonate may impair mental and/or physical abilities. Caution patients about activities requiring alertness (e.g., operating vehicles or machinery). A condition known as Brugada Syndrome may pre-exist and be unmasked by lithium therapy. Brugada Syndrome is a heart disorder characterized by abnormal electrocardiographic (ECG) findings and risk of sudden death. Patients should be advised to seek immediate emergency assistance if they experience fainting, light-headedness, abnormal heart beats, or shortness of breath because they may have a potentially life-threatening heart disorder known as Brugada Syndrome. Drug Interactions Caution should be used when lithium and diuretics are used concomitantly because diuretic-induced sodium loss may reduce the renal clearance of lithium and increase serum lithium levels with risk of lithium toxicity. Patients receiving such combined therapy should have serum lithium levels monitored closely and the lithium dosage adjusted if necessary. Lithium levels should be closely monitored when patients initiate or discontinue NSAID use. In some cases, lithium toxicity has resulted from interactions between an NSAID and lithium. Indomethacin and piroxicam have been reported to increase significantly steady-state plasma lithium concentrations. There is also evidence that other nonsteroidal anti-inflammatory agents, including the selective cyclooxygenase-2 (COX-2) inhibitors, have the same effect. In a study conducted in healthy subjects, mean steady-state lithium plasma levels increased approximately 17% in subjects receiving lithium 450 mg b.i.d. with celecoxib 200 mg b.i.d. as compared to subjects receiving lithium alone. Concomitant use of lithium with a Sodium-Glucose Cotransporter 2 (SGLT2) inhibitor may decrease serum lithium concentrations.

cts, mean steady-state lithium plasma levels increased approximately 17% in subjects receiving lithium 450 mg b.i.d. with celecoxib 200 mg b.i.d. as compared to subjects receiving lithium alone. Concomitant use of lithium with a Sodium-Glucose Cotransporter 2 (SGLT2) inhibitor may decrease serum lithium concentrations. Monitor serum lithium concentration more frequently during SGLT2 inhibitor initiation and dosage changes. Concurrent use of metronidazole with lithium may provoke lithium toxicity due to reduced renal clearance. Patients receiving such combined therapy should be monitored closely. There is evidence that angiotensin-converting enzyme inhibitors, such as enalapril and captopril, and angiotension II receptor antagonists, such as losartan, may substantially increase steady-state plasma lithium levels, sometimes resulting in lithium toxicity. When such combinations are used, lithium dosage may need to be decreased, and plasma lithium levels should be measured more often. Concurrent use of calcium channel blocking agents with lithium may increase the risk of neurotoxicity in the form of ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus. Caution is recommended. Concomitant administration of lithium with serotonergic drugs can precipitate serotonin syndrome. Monitor patients for signs and symptoms of serotonin syndrome, particularly during lithium initiation. If serotonin syndrome occurs, consider discontinuation of lithium and/or concomitant serotonergic drugs. Examples of serotonergic drugs include selective serotonin reuptake inhibitors (SSRI), serotonin and norepinephrine reuptake inhibitors (SNRI), and monoamine oxidase inhibitors (MAOI). The following drugs can lower serum lithium concentrations by increasing urinary lithium excretion: acetazolamide, urea, xanthine preparations, and alkalinizing agents such as sodium bicarbonate. Concomitant administration of methyldopa, phenytoin, or carbamazepine with lithium may increase the risk of toxic effects of these drugs. Concomitant extended use of iodide preparations, especially potassium iodide, with lithium may produce hypothyroidism. Usage in Pregnancy Teratogenic Effects: [See WARNINGS ]. Usage in Nursing Mothers Because of the potential for serious adverse reactions in nursing infants and neonates from lithium, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother [see WARNINGS ]. Pediatric Use Safety and effectiveness in pediatric patients below the age of 12 have not been established [see WARNINGS ]. Geriatric Use Clinical studies of Lithium Carbonate Extended-Release Tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, 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 therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

General The ability to tolerate lithium is greater during the acute manic phase and decreases when manic symptoms subside [see DOSAGE AND ADMINISTRATION ]. The distribution space of lithium approximates that of total body water. Lithium is primarily excreted in urine with insignificant excretion in feces. Renal excretion of lithium is proportional to its plasma concentration. The half-life of elimination of lithium is approximately 24 hours. Lithium decreases sodium reabsorption by the renal tubules which could lead to sodium depletion. Therefore, it is essential for the patient to maintain a normal diet, including salt, and an adequate fluid intake (2,500 to 3,000 mL) at least during the initial stabilization period. Decreased tolerance to lithium has been reported to ensue from protracted sweating or diarrhea and, if such occur, supplemental fluid and salt should be administered under careful medical supervision and lithium intake reduced or suspended until the condition is resolved. In addition to sweating and diarrhea, concomitant infection with elevated temperatures may also necessitate a temporary reduction or cessation of medication. Previously existing underlying thyroid disorders do not necessarily constitute a contraindication to lithium treatment; where hypothyroidism preexists, careful monitoring of thyroid function during lithium stabilization and maintenance allows for correction of changing thyroid parameters, if any; where hypothyroidism occurs during lithium stabilization and maintenance, supplemental thyroid treatment may be used.

Information for Patients Lithium carbonate may impair mental and/or physical abilities. Caution patients about activities requiring alertness (e.g., operating vehicles or machinery). A condition known as Brugada Syndrome may pre-exist and be unmasked by lithium therapy. Brugada Syndrome is a heart disorder characterized by abnormal electrocardiographic (ECG) findings and risk of sudden death. Patients should be advised to seek immediate emergency assistance if they experience fainting, light-headedness, abnormal heart beats, or shortness of breath because they may have a potentially life-threatening heart disorder known as Brugada Syndrome.

Drug Interactions Caution should be used when lithium and diuretics are used concomitantly because diuretic-induced sodium loss may reduce the renal clearance of lithium and increase serum lithium levels with risk of lithium toxicity. Patients receiving such combined therapy should have serum lithium levels monitored closely and the lithium dosage adjusted if necessary. Lithium levels should be closely monitored when patients initiate or discontinue NSAID use. In some cases, lithium toxicity has resulted from interactions between an NSAID and lithium. Indomethacin and piroxicam have been reported to increase significantly steady-state plasma lithium concentrations. There is also evidence that other nonsteroidal anti-inflammatory agents, including the selective cyclooxygenase-2 (COX-2) inhibitors, have the same effect. In a study conducted in healthy subjects, mean steady-state lithium plasma levels increased approximately 17% in subjects receiving lithium 450 mg b.i.d. with celecoxib 200 mg b.i.d. as compared to subjects receiving lithium alone. Concomitant use of lithium with a Sodium-Glucose Cotransporter 2 (SGLT2) inhibitor may decrease serum lithium concentrations. Monitor serum lithium concentration more frequently during SGLT2 inhibitor initiation and dosage changes. Concurrent use of metronidazole with lithium may provoke lithium toxicity due to reduced renal clearance. Patients receiving such combined therapy should be monitored closely. There is evidence that angiotensin-converting enzyme inhibitors, such as enalapril and captopril, and angiotension II receptor antagonists, such as losartan, may substantially increase steady-state plasma lithium levels, sometimes resulting in lithium toxicity. When such combinations are used, lithium dosage may need to be decreased, and plasma lithium levels should be measured more often. Concurrent use of calcium channel blocking agents with lithium may increase the risk of neurotoxicity in the form of ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus. Caution is recommended. Concomitant administration of lithium with serotonergic drugs can precipitate serotonin syndrome. Monitor patients for signs and symptoms of serotonin syndrome, particularly during lithium initiation. If serotonin syndrome occurs, consider discontinuation of lithium and/or concomitant serotonergic drugs. Examples of serotonergic drugs include selective serotonin reuptake inhibitors (SSRI), serotonin and norepinephrine reuptake inhibitors (SNRI), and monoamine oxidase inhibitors (MAOI). The following drugs can lower serum lithium concentrations by increasing urinary lithium excretion: acetazolamide, urea, xanthine preparations, and alkalinizing agents such as sodium bicarbonate. Concomitant administration of methyldopa, phenytoin, or carbamazepine with lithium may increase the risk of toxic effects of these drugs. Concomitant extended use of iodide preparations, especially potassium iodide, with lithium may produce hypothyroidism. Usage in Pregnancy Teratogenic Effects: [See WARNINGS ].

Geriatric Use Clinical studies of Lithium Carbonate Extended-Release Tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, 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 therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

ADVERSE REACTIONS The occurrence and severity of adverse reactions are generally directly related to serum lithium concentrations as well as to individual patient sensitivity to lithium, and generally occur more frequently and with greater severity at higher concentrations. Adverse reactions may be encountered at serum lithium levels below 1.5 mEq/L. Mild to moderate adverse reactions may occur at levels from 1.5 to 2.5 mEq/L, and moderate to severe reactions may be seen at levels of 2 mEq/L and above. Fine hand tremor, polyuria, and mild thirst may occur during initial therapy for the acute manic phase, and may persist throughout treatment. Transient and mild nausea and general discomfort may also appear during the first few days of lithium administration. These side effects usually subside with continued treatment or a temporary reduction or cessation of dosage. If persistent, cessation of lithium therapy may be required. Diarrhea, vomiting, drowsiness, muscular weakness, and lack of coordination may be early signs of lithium intoxication, and can occur at lithium levels below 2 mEq/L. At higher levels, ataxia, giddiness, tinnitus, blurred vision, and a large output of dilute urine may be seen. Serum lithium levels above 3 mEq/L may produce a complex clinical picture, involving multiple organs and organ systems. Serum lithium levels should not be permitted to exceed 2 mEq/L during the acute treatment phase. The following reactions have been reported and appear to be related to serum lithium levels, including levels within the therapeutic range: Neuromuscular/Central Nervous System: Tremor, muscle hyperirritability (fasciculations, twitching, clonic movements of whole limbs), hypertonicity, ataxia, choreo-athetotic movements, hyperactive deep tendon reflex, extrapyramidal symptoms including acute dystonia, cogwheel rigidity, blackout spells, epileptiform seizures, slurred speech, dizziness, vertigo, downbeat nystagmus, incontinence of urine or feces, somnolence, psychomotor retardation, restlessness, confusion, stupor, coma, tongue movements, tics, tinnitus, hallucinations, poor memory, slowed intellectual functioning, startled response, worsening of organic brain syndromes, myasthenia gravis (rarely). Cardiovascular: Cardiac arrhythmia, hypotension, peripheral circulatory collapse, bradycardia, sinus node dysfunction with severe bradycardia (which may result in syncope), Unmasking of Brugada Syndrome [see WARNINGS and PRECAUTIONS , Information for Patients ]. Gastrointestinal - Anorexia, nausea, vomiting, diarrhea, gastritis, salivary gland swelling, abdominal pain, excessive salivation, flatulence, indigestion. Genitourinary: Glycosuria, decreased creatinine clearance, albuminuria, oliguria, and symptoms of nephrogenic diabetes insipidus including polyuria, thirst and polydipsia. Dermatologic: Drying and thinning of hair, alopecia, anesthesia of skin, chronic folliculitis, xerosis cutis, psoriasis onset or exacerbation, generalized pruritus with or without rash, cutaneous ulcers, angioedema, drug reaction with eosinophilia and systemic symptoms (DRESS). Autonomic Nervous System: Blurred vision, dry mouth, impotence/sexual dysfunction. Thyroid Abnormalities: Euthyroid goiter and/or hypothyroidism (including myxedema) accompanied by lower T 3 and T 4 .I 131 uptake may be elevated [see PRECAUTIONS ]. Paradoxically, rare cases of hyperthyroidism have been reported.

RESS). Autonomic Nervous System: Blurred vision, dry mouth, impotence/sexual dysfunction. Thyroid Abnormalities: Euthyroid goiter and/or hypothyroidism (including myxedema) accompanied by lower T 3 and T 4 .I 131 uptake may be elevated [see PRECAUTIONS ]. Paradoxically, rare cases of hyperthyroidism have been reported. EEG Changes: Diffuse slowing, widening of the frequency spectrum, potentiation and disorganization of background rhythm. EKG Changes: Reversible flattening, isoelectricity or inversion of T-waves. Miscellaneous: Fatigue, lethargy, transient scotomata, exophthalmos, dehydration, weight loss, leukocytosis, headache, transient hyperglycemia, hypercalcemia, hyperparathyroidism, excessive weight gain, edematous swelling of ankles or wrists, metallic taste, dysgeusia/taste distortion, salty taste, thirst, swollen lips, tightness in chest, swollen and/or painful joints, fever, polyarthralgia, dental caries. Some reports of nephrogenic diabetes insipidus, hyperparathyroidism, and hypothyroidism which persist after lithium discontinuation have been received. A few reports have been received of the development of painful discoloration of fingers and toes and coldness of the extremities within one day of the starting of treatment with lithium. The mechanism through which these symptoms (resembling Raynaud's syndrome) developed is not known. Recovery followed discontinuance.

OVERDOSAGE The toxic levels for lithium (≥ 1.5 mEq/L) are close to the therapeutic levels (0.6 to 1.2 mEq/L). It is therefore important that patients and their families be cautioned to watch for early toxic symptoms and to discontinue the drug and inform the physician should they occur. Toxic symptoms are listed in detail under ADVERSE REACTIONS . Treatment : No specific antidote for lithium poisoning is known. Early symptoms of lithium toxicity can usually be treated by reduction or cessation of dosage of the drug and resumption of the treatment at a lower dose after 24 to 48 hours. In severe cases of lithium poisoning, the first and foremost goal of treatment consists of elimination of this ion from the patient. Treatment is essentially the same as that used in barbiturate poisoning: 1) gastric lavage, 2) correction of fluid and electrolyte imbalance, and 3) regulation of kidney function. Urea, mannitol and aminophylline all produce significant increases in lithium excretion. Hemodialysis is an effective and rapid means of removing the ion from the severely toxic patient. Infection prophylaxis, regular chest X-rays and preservation of adequate respiration are essential.

DOSAGE AND ADMINISTRATION Doses of controlled-release tablets are usually given b.i.d. (approximately 12-hour intervals). When initiating therapy with controlled-release lithium, dosage must be individualized according to serum levels and clinical response. When switching a patient from immediate-release capsules to Lithium Carbonate Extended-Release Tablets, give the same total daily dose when possible. Most patients on maintenance therapy are stabilized on 900 mg daily, e.g., Lithium Carbonate Extended-Release Tablets 450 mg b.i.d. When the previous dosage of immediate-release lithium is not a multiple of 450 mg, e.g., 1,500 mg, initiate Lithium Carbonate Extended-Release Tablets at the multiple of 450 mg nearest to, but below , the original daily dose, i.e., 1,350 mg. When the 2 doses are unequal, give the larger dose in the evening. In the above example, with a total daily dose of 1,350 mg, generally 450 mg of Lithium Carbonate Extended-Release Tablets should be given in the morning and 900 mg of Lithium Carbonate Extended-Release Tablets in the evening. If desired, the total daily dose of 1,350 mg can be given in 3 equal 450-mg doses of Lithium Carbonate Extended-Release Tablets. These patients should be monitored at 1- to 2-week intervals, and dosage adjusted if necessary, until stable and satisfactory serum levels and clinical state are achieved. When patients require closer titration than that available with doses of Lithium Carbonate Extended-Release Tablets in increments of 450 mg, immediate-release capsules should be used. Acute Mania: Optimal patient response to Lithium Carbonate Extended-Release Tablets can usually be established and maintained with 1,800 mg per day in divided doses. Such doses will normally produce the desired serum lithium level ranging between 1 and 1.5 mEq/L. Dosage must be individualized according to serum levels and clinical response. Regular monitoring of the patient’s clinical state and serum lithium levels is necessary. Serum levels should be determined twice per week during the acute phase, and until the serum level and clinical condition of the patient have been stabilized. Long-Term Control: The desirable serum lithium levels are 0.6 to 1.2 mEq/L. Dosage will vary from one individual to another, but usually 900 mg to 1,200 mg per day in divided doses will maintain this level. Serum lithium levels in uncomplicated cases receiving maintenance therapy during remission should be monitored at least every two months. Patients unusually sensitive to lithium may exhibit toxic signs at serum levels below 1 mEq/L. Important Considerations Blood samples for serum lithium determinations should be drawn immediately prior to the next dose when lithium concentrations are relatively stable (i.e., 8 to 12 hours after the previous dose). Total reliance must not be placed on serum levels alone. Accurate patient evaluation requires both clinical and laboratory analysis. Elderly patients often respond to reduced dosage, and may exhibit signs of toxicity at serum levels ordinarily tolerated by younger patients. Lithium Carbonate Extended-Release Tablets must be swallowed whole and never chewed or crushed.

HOW SUPPLIED Lithium Carbonate Extended-Release Tablets USP, 450 mg are supplied as off-white to pale yellow, circular, beveled edged, biconvex uncoated tablets with ‘224’ debossed on one side, ‘G’ and a break line debossed on the other side, in bottles of 30’s, 100’s, and 1,000’s. The tablets meet the requirements of USP Dissolution Test 2 in the USP monograph for Lithium Carbonate Extended-release Tablets USP. Bottles of 30 NDC 68462-224-30 Bottles of 100 NDC 68462-224-01 Bottles of 1,000 NDC 68462-224-10

Storage Conditions Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Distributed by: Glenmark Pharmaceuticals Inc., USA Elmwood Park, NJ 07407 Questions? 1 (888) 721-7115 www.glenmarkpharma-us.com August 2025

WARNING: LITHIUM TOXICITY Lithium toxicity is closely related to serum lithium concentrations, and can occur at doses close to therapeutic concentrations. Facilities for prompt and accurate serum lithium determinations should be available before initiating treatment [see Dosage and Administration ( 2.3 ), Warnings and Precautions ( 5.1 )]. WARNING: LITHIUM TOXICITY See full prescribing information for complete boxed warning. Lithium toxicity is closely related to serum lithium concentrations, and can occur at doses close to therapeutic concentrations. Facilities for prompt and accurate serum lithium determinations should be available before initiating therapy ( 2.3 , 5.1 ).

1 INDICATIONS AND USAGE Lithium is a mood-stabilizing agent indicated as monotherapy for the treatment of bipolar I disorder: • Treatment of acute manic and mixed episodes in patients 7 years and older [see Clinical Studies ( 14 )] • Maintenance treatment in patients 7 years and older [see Clinical Studies (14)] Lithium is a mood-stabilizing agent indicated as monotherapy for the treatment of bipolar I disorder: • Treatment of acute manic and mixed episodes in patients 7 years and older ( 1 ) • Maintenance treatment in patients 7 years and older ( 1 )

2 DOSAGE AND ADMINISTRATION Recommended starting dosage for adults and pediatric patients over 30 kg ( 2.2 ): Capsules: 300 mg, three times daily Recommended starting dosage for pediatric patients 20 to 30 kg ( 2.2 ): Capsules: 300 mg twice daily Obtain serum lithium concentration assay after 3 days, drawn 12 hours after the last oral dose and regularly until patient is stabilized. Acute Manic or Mixed Episodes (patients 7 years and older): Titrate to serum lithium concentrations 0.8 to 1.2 mEq/L ( 2.2 ). Maintenance Treatment for Bipolar I Disorder (patients 7 years and older): Titrate to serum lithium concentrations 0.8 to 1 mEq/L ( 2.2 ). Pre-treatment Screening: Evaluate renal function, vital signs, electrolytes, thyroid function, concurrent medications, and pregnancy status ( 2.1 ). Mild to Moderate Renal Impairment (CLer 30 to 89 mL/min): Start with dosages less than those for patients with normal renal function, titrate slowly with frequent monitoring ( 2.5 ). Severe Renal Impairment (CLer < 30 mL/min): Avoid use of lithium ( 2.5 ). 2.1 Pre-treatment Screening Before initiating treatment with lithium, renal function, vital signs, serum electrolytes, and thyroid function should be evaluated. Concurrent medications should be assessed, and if the patient is a woman of childbearing potential, pregnancy status and potential should be considered. 2.2 Recommended Dosage See Table 1 for dosage recommendations for acute and maintenance treatment of bipolar I disorder in adult and pediatric patients (7 to 17 years). Obtain serum lithium concentration assay after 3 days, drawn 12 hours after the last oral dose and regularly until patient is stabilized. Fine hand tremor, polyuria, and thirst may occur during initial therapy for the acute manic phase and may persist throughout treatment. Nausea and general discomfort may also appear during the first few days of lithium administration. These adverse reactions may subside with continued treatment, concomitant administration with food, or temporary reduction or cessation of dosage. Table 1. Lithium Dosing for Bipolar I Disorder Patient Group Formulation Starting Dose Dose Titration Acute Goal Maintenance Goal Serum Level Usual Dose Serum Level Usual Dose Adult and Pediatric Patients over 30 kg Capsules 300 mg three times daily 300 mg every 3 days 0.8 to 1.2 mEq/L 600 mg two to three times daily 0.8 to 1 mEq/L 300 to 600 mg two to three times daily Pediatric Patients 20 to 30 kg Capsules 300 mg twice daily 300 mg weekly 600 to 1500 mg in divided doses daily 600 to 1200 mg in divided doses daily 2.3 Serum Lithium Monitoring Blood samples for serum lithium determination should be drawn immediately prior to the next dose when lithium concentrations are relatively stable (i.e., 12 hours after the previous dose). Total reliance must not be placed on serum concentrations alone. Accurate patient evaluation requires both clinical and laboratory analysis. In addition to regular monitoring of serum lithium concentrations for patients on maintenance treatment, serum lithium concentrations should be monitored after any change in dosage, concurrent medication (e.g., diuretics, non-steroidal anti-inflammatory drugs, renin-angiotensin system antagonists, or metronidazole), marked increase or decrease in routinely performed strenuous physical activity (such as an exercise program) and in the event of a concomitant disease [see Boxed Warning , Warnings and Precautions ( 5.1 ), Drug Interactions ( 7.1 )].

idal anti-inflammatory drugs, renin-angiotensin system antagonists, or metronidazole), marked increase or decrease in routinely performed strenuous physical activity (such as an exercise program) and in the event of a concomitant disease [see Boxed Warning , Warnings and Precautions ( 5.1 ), Drug Interactions ( 7.1 )]. Patients abnormally sensitive to lithium may exhibit toxic signs at serum concentrations that are within what is considered the therapeutic range. Geriatric patients often respond to reduced dosage, and may exhibit signs of toxicity at serum concentrations ordinarily tolerated by other patients [see Specific Populations ( 8.5 )]. 2.4 Dosage Adjustments during Pregnancy and the Postpartum Period If the decision is made to continue lithium treatment during pregnancy, monitor serum lithium concentrations and adjust the dosage as needed in a pregnant woman because renal lithium clearance increases during pregnancy. Avoid sodium restriction or diuretic administration. To decrease the risk of postpartum lithium intoxication, decrease or discontinue lithium therapy two to three days before the expected delivery date to reduce neonatal concentrations and reduce the risk of maternal lithium intoxication due to the change in vascular volume which occurs during delivery. At delivery, vascular volume rapidly decreases and the renal clearance of lithium may decrease to pre-pregnancy concentrations. Restart treatment at the preconception dose when the patient is medically stable after delivery with careful monitoring of serum lithium concentrations [see Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.1 )]. 2.5 Dosage Adjustments for Patients with Renal Impairment Start patients with mild to moderately impaired renal function (creatinine clearance 30 to 89 mL/min evaluated by Cockcroft-Gault) with dosages less than those for patients with normal renal function [see Dosage and Administration ( 2.2 )] . Titrate slowly while frequently monitoring serum lithium concentrations and monitoring for signs of lithium toxicity. Lithium is not recommended for use in patients with severe renal impairment (creatinine clearance less than 30 mL/min evaluated by Cockcroft-Gault) [see Use in Specific Populations ( 8.6 )] .

3 DOSAGE FORMS AND STRENGTHS Each 600 mg capsule for oral administration contains: lithium carbonate, USP 600 mg and is a two piece hard gelatin capsules (size ‘0’ elongated) pink colored cap and light gray colored body imprinted with ‘600’ on the body and ‘G222’ on the cap. Capsules: 600 mg of lithium carbonate, USP ( 3 )

4 CONTRAINDICATIONS Lithium is contraindicated in patients with known hypersensitivity to any inactive ingredient in the lithium carbonate capsule [see Adverse Reactions ( 6 )]. Known hypersensitivity to any inactive ingredient in the drug product. ( 4 )

5 WARNINGS AND PRECAUTIONS Lithium-Induced Polyuria: May develop during initiation of treatment. Increases risk of lithium toxicity. Educate patient to avoid dehydration. Monitor for lithium toxicity and metabolic acidosis. Discontinue lithium or treat with amiloride as a therapeutic agent ( 5.2 ). Hyponatremia: Symptoms are more severe with faster-onset hyponatremia. Dehydration from protracted sweating, diarrhea, or elevated temperatures from infection increases risk of hyponatremia and lithium toxicity. Educate patients on maintaining a normal diet with salt and staying hydrated. Monitor for and treat hyponatremia and lithium toxicity, which may necessitate a temporary reduction or cessation of lithium and infusion of serum sodium ( 5.3 ). Lithium-Induced Chronic Kidney Disease: Associated with structural changes in patients on chronic lithium therapy. Monitor kidney function during treatment with lithium ( 5.4 ). Encephalopathic Syndrome: Increased risk in patients treated with lithium and an antipsychotic. Monitor routinely for changes to cognitive function ( 5.5 ). Hypothyroidism and Hyperthyroidism: Monitor thyroid function regularly ( 5.7 ). Hypercalcemia and Hyperparathyroidism: Associated with long-term lithium use. Monitor serum calcium ( 5.8 ). 5.1 Lithium Toxicity The toxic concentrations for lithium (≥1.5 mEq/L) are close to the therapeutic range (0.8 to 1.2mEq/L). Some patients abnormally sensitive to lithium may exhibit toxic signs at serum concentrations that are considered within the therapeutic range [see Boxed Warning, Dosage and Administration ( 2.3 )] . Lithium may take up to 24 hours to distribute into brain tissue, so occurrence of acute toxicity symptoms may be delayed. Neurological signs of lithium toxicity range from mild neurological adverse reactions such as fine tremor, lightheadedness, lack of coordination, and weakness; to moderate manifestations like giddiness, apathy, drowsiness, hyperreflexia, muscle twitching, ataxia, blurred vision, tinnitus, and slurred speech; and severe manifestations such as clonus, confusion, seizure, coma, and death. In rare cases, neurological sequelae may persist despite discontinuing lithium treatment and may be associated with cerebellar atrophy. Cardiac manifestations involve electrocardiographic changes, such as prolonged QT interval, ST and T-wave changes and myocarditis. Renal manifestations include urine concentrating defect, nephrogenic diabetes insipidus, and renal failure. Respiratory manifestations include dyspnea, aspiration pneumonia, and respiratory failure. Gastrointestinal manifestations include nausea, vomiting, diarrhea, and bloating. No specific antidote for lithium poisoning is known [see Overdosage ( 10 )] . The risk of lithium toxicity is increased by: Recent onset of concurrent febrile illness Concomitant administration of drugs which increase lithium serum concentrations by pharmacokinetic interactions or drugs affecting kidney function [see Drug Interactions ( 7 )] . Acute ingestion Impaired renal function Volume depletion or dehydration Significant cardiovascular disease Changes in electrolyte concentrations (especially sodium and potassium) Monitor for signs and symptoms of lithium toxicity. If symptoms occur, decrease dosage or discontinue lithium treatment.

nteractions ( 7 )] . Acute ingestion Impaired renal function Volume depletion or dehydration Significant cardiovascular disease Changes in electrolyte concentrations (especially sodium and potassium) Monitor for signs and symptoms of lithium toxicity. If symptoms occur, decrease dosage or discontinue lithium treatment. 5.2 Lithium-Induced Polyuria Chronic lithium treatment may be associated with diminution of renal concentrating ability, occasionally presenting as nephrogenic diabetes insipidus, with polyuria and polydipsia. The concentrating defect and natriuretic effect characteristic of this condition may develop within weeks of lithium initiation. Lithium can also cause renal tubular acidosis, resulting in hyperchloremic metabolic acidosis. Such patients should be carefully managed to avoid dehydration with resulting lithium retention and toxicity. This condition is usually reversible when lithium is discontinued, although for patients treated with long-term lithium, nephrogenic diabetes insipidus may be only partly reversible upon discontinuation of lithium. Amiloride may be considered as a therapeutic agent for lithium-induced nephrogenic diabetes insipidus. 5.3 Hyponatremia Lithium can cause hyponatremia by decreasing sodium reabsorption by the renal tubules, leading to sodium depletion. Therefore, it is essential for patients receiving lithium treatment to maintain a normal diet, including salt, and an adequate fluid intake (2500 to 3000 mL) at least during the initial stabilization period. Decreased tolerance to lithium has also been reported to ensue from protracted sweating or diarrhea and, if such occur, supplemental fluid and salt should be administered under careful medical supervision and lithium intake reduced or suspended until the condition is resolved. In addition, concomitant infection with elevated temperatures may also necessitate a temporary reduction or cessation of medication. Symptoms are also more severe with faster-onset hyponatremia. Mild hyponatremia (i.e., serum Na > 120 mEq/L) can be asymptomatic. Below this threshold, clinical signs are usually present, consisting mainly of changes in mental status, such as altered personality, lethargy, and confusion. For more severe hyponatremia (serum Na < 115 mEq/L), stupor, neuromuscular hyperexcitability, hyperreflexia, seizures, coma, and death can result. During treatment of hyponatremia, serum sodium should not be elevated by more than 10 to 12 mEq/L in 24 hours, or 18 mEq/L in 48 hours. In the case of severe hyponatremia where severe neurologic symptoms are present, a faster infusion rate to correct serum sodium concentration may be needed. Patients rapidly treated or with serum sodium <120mEq/L are more at risk of developing osmotic demyelination syndrome (previously called central pontine myelinolysis). Occurrence is more common among patients with alcoholism, undernutrition, or other chronic debilitating illness. Common signs include flaccid paralysis, dysarthria. In severe cases with extended lesions patients may develop a locked-in syndrome (generalized motor paralysis). Damage often is permanent. If neurologic symptoms start to develop during treatment of hyponatremia, serum sodium correction should be suspended to mitigate the development of permanent neurologic damage. 5.4 Lithium-Induced Chronic Kidney Disease The predominant form of chronic renal disease associated with long-term lithium treatment is a chronic tubulointerstitial nephropathy (CTIN). The biopsy findings in patients with lithium induced CTIN include tubular atrophy, interstitial fibrosis, sclerotic glomeruli, tubular dilation, and nephron atrophy with cyst formation. The relationship between renal function and morphologic changes and their association with lithium treatment has not been established.

The biopsy findings in patients with lithium induced CTIN include tubular atrophy, interstitial fibrosis, sclerotic glomeruli, tubular dilation, and nephron atrophy with cyst formation. The relationship between renal function and morphologic changes and their association with lithium treatment has not been established. CTIN patients might present with nephrotic proteinuria (>3g/dL), worsening renal insufficiency and/or nephrogenic diabetes insipidus. Postmarketing cases consistent with nephrotic syndrome in patients with or without CTIN have also been reported. The biopsy findings in patients with nephrotic syndrome include minimal change disease and focal segmental glomerulosclerosis. The discontinuation of lithium in patients with nephrotic syndrome has resulted in remission of nephrotic syndrome. Kidney function should be assessed prior to and during lithium treatment. Routine urinalysis and other tests may be used to evaluate tubular function (e.g., urine specific gravity or osmolality following a period of water deprivation, or 24-hour urine volume) and glomerular function (e.g., serum creatinine, creatinine clearance, or proteinuria). During lithium treatment, progressive or sudden changes in renal function, even within the normal range, indicate the need for re-evaluation of treatment. 5.5 Encephalopathic Syndrome An encephalopathic syndrome, characterized by weakness, lethargy, fever, tremulousness and confusion, extrapyramidal symptoms, leukocytosis, elevated serum enzymes, BUN and fasting blood glucose, has occurred in patients treated with lithium and an antipsychotic. In some instances, the syndrome was followed by irreversible brain damage. Because of a possible causal relationship between these events and the concomitant administration of lithium and antipsychotics, patients receiving such combined treatment should be monitored closely for early evidence of neurological toxicity and treatment discontinued promptly if such signs appear. This encephalopathic syndrome may be similar to or the same as neuroleptic malignant syndrome (NMS). 5.6 Serotonin Syndrome Lithium can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, triptans, tricyclic antidepressants, fentanyl, tramadol, tryptophan, buspirone, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [see Drug Interactions ( 7.1 )] . 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). Monitor all patients taking lithium for the emergence of serotonin syndrome. Discontinue treatment with lithium and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of lithium with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms. 5.7 Hypothyroidism or Hyperthyroidism Lithium is concentrated within the thyroid and can inhibit thyroid synthesis and release which can lead to hypothyroidism. Where hypothyroidism exists, careful monitoring of thyroid function during lithium stabilization and maintenance allows for correction of changing thyroid parameters, if any.

6 ADVERSE REACTIONS The following adverse reactions are described in greater detail in other sections: Acute Lithium Toxicity [see Warnings and Precautions ( 5.1 )] Lithium-Induced Polyuria [see Warnings and Precautions ( 5.2 )] Hyponatremia [see Warnings and Precautions ( 5.3 )] Lithium-Induced Chronic Kidney Disease [see Warnings and Precautions ( 5.4 )] Encephalopathic Syndrome [see Warnings and Precautions ( 5.5 )] Serotonin Syndrome [see Warnings and Precautions ( 5.6 )] Hypothyroidism or Hyperthyroidism [see Warnings and Precautions ( 5.7 )] Hypercalcemia and Hyperparathyroidism [see Warnings and Precautions ( 5.8 )] Unmasking of Brugada Syndrome [see Warnings and Precautions ( 5.9 )] Pseudotumor Cerebri [see Warnings and Precautions ( 5.10 )] Common Adverse Reactions: • Adult Patients: fine hand tremor, polyuria, mild thirst, nausea, general discomfort during initial treatment ( 6 ) • Pediatric Patients (7 to 17 years): nausea/vomiting, polyuria, thyroid abnormalities, tremor, thirst/polydipsia, dizziness, rash/dermatitis, ataxia/gait disturbance, decreased appetite, and blurry vision ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Glenmark Pharmaceuticals Inc., USA at 1 (888) 721-7115 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Pediatric Patients (7 to 17 years): Bipolar I Disorder : The following findings are based on an 8-week, placebo-controlled study for acute manic or mixed episodes of bipolar I disorder in pediatric patients 7 to 17 years (N= 81). In this study, lithium was administered at daily doses ranging from 300 to 3600 (mean dose 1483 mg ± 584) with serum levels ranging from 0 to 2 (mean level 0.98 mEq/L ± 0.47). Common Adverse Reactions (incidence ≥ 5% and at least twice the rate of placebo) : nausea/vomiting, polyuria, thyroid abnormalities, tremor, thirst/polydipsia, dizziness, rash/dermatitis, ataxia/gait disturbance, decreased appetite, and blurry vision. Adverse Reactions Occurring at an Incidence of 2% or More in Lithium-Treated Pediatric Patients : Adverse reactions associated with the use of lithium (incidence of 2% or greater, rounded to the nearest percent, and lithium incidence greater than placebo) that occurred during acute therapy (up to 8-weeks in pediatric patients with bipolar disorder) are shown in Table 3. Table 3: Adverse Reactions Reported in 2% or More of Pediatric Patients on Lithium and That Occurred at Greater Incidence Than in the Placebo Group in the 8-Week Acute Bipolar Trial System Organ Class/ Preferred Term Placebo N=28 % Lithium N=53 % Gastrointestinal Disorders Nausea/vomiting 29 57 General Disorders Fatigue 4 26 Genitourinary Disorders Polyuria (Including Enuresis) 14 38 Investigations Increased TSH 0 25 Metabolism and nutrition disorders Thirst/polydipsia 11 28 Decreased appetite 4 9 Nervous system disorders Ataxia/gait disturbance 0 13 Blurry vision 0 9 Disorientation 0 6 Dizziness 7 23 Tremor 7 32 Skin and subcutaneous tissue disorders Rash/dermatitis 0 13 Adult Patients: The following adverse reactions have been identified following use of lithium.

Thirst/polydipsia 11 28 Decreased appetite 4 9 Nervous system disorders Ataxia/gait disturbance 0 13 Blurry vision 0 9 Disorientation 0 6 Dizziness 7 23 Tremor 7 32 Skin and subcutaneous tissue disorders Rash/dermatitis 0 13 Adult Patients: The following adverse reactions have been identified following use of lithium. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Central Nervous System : tremor, muscle hyperirritability (fasciculations, twitching, clonic movements of whole limbs), hypertonicity, ataxia, choreoathetotic movements, hyperactive deep tendon reflexes, extrapyramidal symptoms including acute dystonia, cogwheel rigidity, blackout spells, epileptiform seizures, slurred speech, dizziness, vertigo, downbeat nystagmus, incontinence of urine or feces, somnolence, psychomotor retardation, restlessness, confusion, stupor, coma, tongue movements, tics, tinnitus, hallucinations, poor memory, slowed intellectual functioning, startled response, worsening of organic brain syndromes, myasthenic syndromes (rarely). EEG Changes: diffuse slowing, widening of frequency spectrum, potentiation and disorganization of background rhythm. Cardiovascula r: conduction disturbance (mostly sinus node dysfunction with possibly severe sinus bradycardia and sinoatrial block), ventricular tachyarrhythmia, peripheral vasculopathy (resembling Raynaud’s Syndrome). ECG Changes : reversible flattening, isoelectricity or rarely inversion of T-waves, prolongation of the QTc interval. Gastrointestinal : anorexia, nausea, vomiting, diarrhea, gastritis, salivary gland swelling, abdominal pain, excessive salivation, flatulence, indigestion. Genitourinary : glycosuria, decreased creatinine clearance, albuminuria, oliguria, and symptoms of nephrogenic diabetes insipidus including polyuria, thirst, and polydipsia. Dermatologic : drying and thinning of hair, alopecia, anesthesia of skin, chronic folliculitis, xerosis cutis, psoriasis onset or exacerbation, generalized pruritus with or without rash, cutaneous ulcers, angioedema, drug reaction with eosinophilia and systemic symptoms (DRESS). Autonomic Nervous System: blurred vision, dry mouth, impotence/sexual dysfunction. Miscellaneous : fatigue, lethargy, transient scotoma, exopthalmos, dehydration, weight loss, leukocytosis, headache, transient hyperglycemia, hypermagnesemia, excessive weight gain, edematous swelling of ankles or wrists, dysgeusia/taste distortion (e.g., metallic or salty taste), thirst, swollen lips, tightness in chest, swollen and/or painful joints, fever, polyarthralgia, and dental caries.

<table width="100%"><col width="37%"/><col width="34%"/><col width="30%"/><tbody><tr><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">System Organ Class/</content></paragraph><paragraph><content styleCode="bold">Preferred Term</content></paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Placebo N=28</content></paragraph><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Lithium N=53</content></paragraph><paragraph><content styleCode="bold">%</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Gastrointestinal Disorders</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="top"/><td styleCode="Rrule Lrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><list listType="unordered"><item>Nausea/vomiting</item></list></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>29</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>57</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">General Disorders</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="top"/><td styleCode="Rrule Lrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><list listType="unordered"><item>Fatigue</item></list></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>26</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Genitourinary Disorders</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="top"/><td styleCode="Rrule Lrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><list listType="unordered"><item>Polyuria (Including Enuresis)</item></list></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>38</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Investigations</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="top"/><td styleCode="Rrule Lrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><list listType="unordered"><item>Increased TSH</item></list></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>25</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Metabolism and nutrition disorders</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="top"/><td styleCode="Rrule Lrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><list listType="unordered"><item>Thirst/polydipsia</item></list></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>11</paragraph></td><td align="center" styleCode="Rrule Lrul

top"/><td styleCode="Rrule Lrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><list listType="unordered"><item>Thirst/polydipsia</item></list></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>11</paragraph></td><td align="center" styleCode="Rrule Lrul e Botrule " valign="top"><paragraph>28</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><list listType="unordered"><item>Decreased appetite</item></list></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>4</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>9</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Nervous system disorders</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="top"/><td styleCode="Rrule Lrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><list listType="unordered"><item>Ataxia/gait disturbance</item></list></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>13</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><list listType="unordered"><item>Blurry vision</item></list></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>9</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><list listType="unordered"><item>Disorientation</item></list></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>6</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><list listType="unordered"><item>Dizziness</item></list></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>7</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>23</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><list listType="unordered"><item>Tremor</item></list></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>7</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>32</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Skin and subcutaneous tissue</content></paragraph><paragraph><content styleCode="bold">disorders</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="top"/><td styleCode="Rrule Lrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Botrule Lrule " valign="top"><list listType="unordered"><item>Rash/dermatitis</item></list></td><td align="center" styleCode="Rrule Botrule Lrule " valign="top"><paragraph>0</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule " valign="top"><paragraph>13</paragraph></td></tr></tbody></table>

7 DRUG INTERACTIONS Diuretics, NSAID, renin-angiotensin system antagonists, or metronidazole may increase lithium serum concentrations. Recommend frequent monitoring of serum lithium concentration and adjust dosage when necessary. ( 2.3 , 7.1 ) Serotonergic Agents: Increased risk of serotonin syndrome when co-administered with lithium. ( 5.6 , 7.1 ) Antipsychotics: There have been reports of neurologic adverse reactions in patients treated with lithium and an antipsychotic, ranging from extrapyramidal symptoms to neuroleptic malignant syndrome. ( 5.5 , 7.1 ) 7.1 Drugs Having Clinically Important Interactions with Lithium Table 4: Clinically Important Drug Interactions with Lithium Diuretics Clinical Impact: Diuretic-induced sodium loss may reduce lithium clearance and increase serum lithium concentrations . Intervention: More frequent monitoring of serum electrolyte and lithium concentrations. Reduce lithium dosage based on serum lithium concentration and clinical response [see Dosage and Administration ( 2.3 ), Warning and Precautions ( 5.3 )] . Non-Steroidal Anti-inflammatory Drugs (NSAID) Clinical Impact: NSAID decrease renal blood flow, resulting in decreased renal clearance and increased serum lithium concentrations. Intervention: More frequent serum lithium concentration monitoring. Reduce lithium dosage based on serum lithium concentration and clinical response [see Dosage and Administration ( 2.3 )] . Renin-Angiotensin System Antagonists Clinical Impact: Concomitant use increase steady-state serum lithium concentrations. Intervention: More frequent monitoring of serum lithium concentration. Reduce lithium dosage based on serum lithium concentration and clinical response [see Dosage and Administration ( 2.3 )] . Serotonergic Drugs Clinical Impact: Concomitant use can precipitate serotonin syndrome. Intervention: Monitor patients for signs and symptoms of serotonin syndrome, particularly during lithium initiation. If serotonin syndrome occurs, consider discontinuation of lithium and/or concomitant serotonergic drugs [see Warnings and Precautions ( 5.6 )] . Nitroimidazole Antibiotics Clinical Impact: Concomitant use may increase serum lithium concentrations due to reduced renal clearance. Intervention: More frequent monitoring of serum lithium concentration. Reduce lithium dosage based on serum lithium concentration and clinical response [see Dosage and Administration ( 2.3 )] . Acetazolamide, Urea, Xanthine Preparations, Alkalinizing Agents Clinical Impact: Concomitant use can lower serum lithium concentrations by increasing urinary lithium excretion. Intervention: More frequent serum lithium concentration monitoring. Increase lithium dosage based on serum lithium concentration and clinical response [see Dosage and Administration ( 2.3 )] . Methyldopa, Phenytoin and Carbamazepine Clinical Impact: Concomitant use may increase risk of adverse reactions of these drugs. Intervention: Monitor patients closely for adverse reactions of methyldopa, phenytoin, and carbamazepine. Iodide Preparations Clinical Impact: Concomitant use may produce hypothyroidism. Intervention: Monitor patients for signs or symptoms of hypothyroidism [see Warnings and Precautions ( 5.7 )] . Calcium Channel Blocking Agents (CCB) Clinical Impact: Concomitant use may increase the risk of neurologic adverse reactions in the form of ataxia, tremors, nausea, vomiting, diarrhea and/or tinnitus. Intervention: Monitor for neurologic adverse reactions.

toms of hypothyroidism [see Warnings and Precautions ( 5.7 )] . Calcium Channel Blocking Agents (CCB) Clinical Impact: Concomitant use may increase the risk of neurologic adverse reactions in the form of ataxia, tremors, nausea, vomiting, diarrhea and/or tinnitus. Intervention: Monitor for neurologic adverse reactions. Atypical and Typical Antipsychotic Drugs Clinical Impact: Reports of neurotoxic reactions in patients treated with both lithium and an antipsychotic, ranging from extrapyramidal symptoms to neuroleptic malignant syndrome, as well as reports of an encephalopathic syndrome in few patients treated with concomitant therapy [see Warnings and Precautions ( 5.5 )] . Intervention: Monitor for neurologic adverse reactions. Sodium-Glucose Cotransporter 2 (SGLT2) inhibitor Clinical Impact: Concomitant use of lithium with an SGLT2 inhibitor may decrease serum lithium concentrations. Intervention: Monitor serum lithium concentration more frequently during SGLT2 inhibitor initiation and dosage changes. Neuromuscular Blocking Agents Clinical Impact: Lithium may prolong the effects of neuromuscular blocking agents. Intervention: Monitor for prolonged paralysis.

<table width="100.38%"><col width="20%"/><col width="80%"/><tbody><tr><td colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">Diuretics</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Clinical Impact:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Diuretic-induced sodium loss may reduce lithium clearance and increase serum lithium concentrations <content styleCode="italics">.</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Intervention:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>More frequent monitoring of serum electrolyte and lithium concentrations. Reduce lithium dosage based on serum lithium concentration and clinical response <content styleCode="italics">[see Dosage and Administration ( <linkHtml href="#ID_5ed0658e-7fc3-443a-b145-e43595336725">2.3</linkHtml>), Warning and Precautions ( <linkHtml href="#ID_a085b83f-f7bb-43f0-9cdc-59abd5399d9b">5.3</linkHtml>)] </content>. </paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Non-Steroidal Anti-inflammatory Drugs (NSAID)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Clinical Impact:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>NSAID decrease renal blood flow, resulting in decreased renal clearance and increased serum lithium concentrations.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Intervention:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>More frequent serum lithium concentration monitoring. Reduce lithium dosage based on serum lithium concentration and clinical response <content styleCode="italics">[see Dosage and Administration ( <linkHtml href="#ID_5ed0658e-7fc3-443a-b145-e43595336725">2.3</linkHtml>)] </content>. </paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Renin-Angiotensin System Antagonists</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Clinical Impact:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Concomitant use increase steady-state serum lithium concentrations.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Intervention:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>More frequent monitoring of serum lithium concentration. Reduce lithium dosage based on serum lithium concentration and clinical response <content styleCode="italics">[see Dosage and Administration ( <linkHtml href="#ID_5ed0658e-7fc3-443a-b145-e43595336725">2.3</linkHtml>)] </content>.

rule " valign="middle"><paragraph>More frequent monitoring of serum lithium concentration. Reduce lithium dosage based on serum lithium concentration and clinical response <content styleCode="italics">[see Dosage and Administration ( <linkHtml href="#ID_5ed0658e-7fc3-443a-b145-e43595336725">2.3</linkHtml>)] </content>. </paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Serotonergic Drugs</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Clinical Impact:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Concomitant use can precipitate serotonin syndrome.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Intervention:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Monitor patients for signs and symptoms of serotonin syndrome, particularly during lithium initiation. If serotonin syndrome occurs, consider discontinuation of lithium and/or concomitant serotonergic drugs <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID_0373b2cf-f4dc-4885-b883-4bb84de17de1">5.6</linkHtml>)] </content>. </paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Nitroimidazole Antibiotics</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Clinical Impact:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Concomitant use may increase serum lithium concentrations due to reduced renal clearance.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Intervention:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>More frequent monitoring of serum lithium concentration. Reduce lithium dosage based on serum lithium concentration and clinical response <content styleCode="italics">[see Dosage and Administration ( <linkHtml href="#ID_5ed0658e-7fc3-443a-b145-e43595336725">2.3</linkHtml>)] </content>. </paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Acetazolamide, Urea, Xanthine Preparations, Alkalinizing Agents</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Clinical Impact:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Concomitant use can lower serum lithium concentrations by increasing urinary lithium excretion.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Intervention:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>More frequent serum lithium concentration monitoring. Increase lithium dosage based on serum lithium concentration and clinical response <content styleCode="italics">[see Dosage and Administration ( <linkHtml href="#ID_5ed0658e-7fc3-443a-b145-e43595336725">2.3</linkHtml>)] </content>.

trule " valign="middle"><paragraph>More frequent serum lithium concentration monitoring. Increase lithium dosage based on serum lithium concentration and clinical response <content styleCode="italics">[see Dosage and Administration ( <linkHtml href="#ID_5ed0658e-7fc3-443a-b145-e43595336725">2.3</linkHtml>)] </content>. </paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Methyldopa, Phenytoin and Carbamazepine</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Clinical Impact:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Concomitant use may increase risk of adverse reactions of these drugs.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Intervention:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Monitor patients closely for adverse reactions of methyldopa, phenytoin, and carbamazepine.</paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Iodide Preparations</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Clinical Impact:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Concomitant use may produce hypothyroidism.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Intervention:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Monitor patients for signs or symptoms of hypothyroidism <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID_58d1337d-296c-443a-ae0d-2870b2021459">5.7</linkHtml>)] </content>. </paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Calcium Channel Blocking Agents (CCB)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Clinical Impact:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Concomitant use may increase the risk of neurologic adverse reactions in the form of ataxia, tremors, nausea, vomiting, diarrhea and/or tinnitus.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Intervention:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Monitor for neurologic adverse reactions.</paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Atypical and Typical Antipsychotic Drugs</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Clinical Impact:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Reports of neurotoxic reactions in patients treated with both lithium and an antipsychotic, ranging from extrapyramidal symptoms to neuroleptic malignant syndrome, as well as reports of an encephalopathic syndrome in few patients treated with concomitant therapy <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID_d0216ef8-8770-42ce-880d-10c1191bf948">5.5</linkHtml>)] </content>.

, ranging from extrapyramidal symptoms to neuroleptic malignant syndrome, as well as reports of an encephalopathic syndrome in few patients treated with concomitant therapy <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID_d0216ef8-8770-42ce-880d-10c1191bf948">5.5</linkHtml>)] </content>. </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Intervention:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Monitor for neurologic adverse reactions.</paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Sodium-Glucose Cotransporter 2 (SGLT2) inhibitor</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Clinical Impact:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Concomitant use of lithium with an SGLT2 inhibitor may decrease serum lithium concentrations.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Intervention:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Monitor serum lithium concentration more frequently during SGLT2 inhibitor initiation and dosage changes.</paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="bold">Neuromuscular Blocking Agents</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph><content styleCode="italics">Clinical Impact:</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>Lithium may prolong the effects of neuromuscular blocking agents.</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="middle"><paragraph><content styleCode="italics">Intervention:</content></paragraph></td><td styleCode="Rrule Botrule Lrule " valign="middle"><paragraph>Monitor for prolonged paralysis.</paragraph></td></tr></tbody></table>

8 USE IN SPECIFIC POPULATIONS Pregnancy: May cause fetal and/or neonatal harm ( 8.1 ) Renal Impairment: Use caution during dose selection, starting with dosages less than those for patients with normal renal function while carefully monitoring for side effects ( 2.5 , 6 ) 8.1 Pregnancy Risk Summary: Lithium may cause harm when administered to a pregnant woman. Early voluntary reports to international birth registries suggested an increase in cardiovascular malformations, especially for Ebstein’s anomaly, with first trimester use of lithium. Subsequent case-control and cohort studies indicate that the increased risk for cardiac malformations is likely to be small; however, the data are insufficient to establish a drug-associated risk. There are concerns for maternal and/or neonatal lithium toxicity during late pregnancy and the postpartum period [see Clinical Considerations]. Published animal developmental and toxicity studies in mice and rats report an increased incidence of fetal mortality, decreased fetal weight, increased fetal skeletal abnormalities, and cleft palate (mouse fetuses only) with oral doses of lithium that produced serum concentrations similar to the human therapeutic range. Other published animal studies report adverse effects on embryonic implantation in rats after lithium administration. Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population(s) is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations: Dose Adjustments During Pregnancy and the Postpartum Period: If the decision is made to continue lithium treatment during pregnancy, serum lithium concentrations should be monitored and the dosage adjusted during pregnancy. Two to three days prior to delivery, lithium dosage should be decreased or discontinued to reduce the risk of maternal and/or neonatal toxicity. Lithium may be restarted in the post-partum period at preconception doses in medically stable patients as long as serum lithium levels are closely monitored [see Dosage and Administration ( 2.4 ), Warnings and Precautions ( 5.1 )]. Fetal/Neonatal Adverse Reactions: Lithium toxicity may occur in neonates who were exposed to lithium in late pregnancy. A floppy baby syndrome including neurological, cardiac, and hepatic abnormalities that are similar to those seen with lithium toxicity in adults have been observed. Symptoms include hypotonia, respiratory distress syndrome, cyanosis, lethargy, feeding difficulties, depressed neonatal reflexes, neonatal depression, apnea, and bradycardia. Monitor neonates and provide supportive care until lithium is excreted and toxic signs disappear, which may take up to 14 days. Consider fetal echocardiography between 16 and 20 weeks gestation in a woman with first trimester lithium exposure because of the potential increased risk of cardiac malformations. 8.2 Lactation Risk Summary: Limited published data reports the presence of lithium carbonate in human milk with breast milk levels measured at 0.12 to 0.7 mEq or 40 to 45% of maternal plasma levels. Infants exposed to lithium during breastfeeding may have plasma levels that are 30 to 40% of maternal plasma levels.

ons. 8.2 Lactation Risk Summary: Limited published data reports the presence of lithium carbonate in human milk with breast milk levels measured at 0.12 to 0.7 mEq or 40 to 45% of maternal plasma levels. Infants exposed to lithium during breastfeeding may have plasma levels that are 30 to 40% of maternal plasma levels. Signs and symptoms of lithium toxicity such as hypertonia, hypothermia, cyanosis, and ECG changes have been reported in some breastfed neonates and infants. Increased prolactin levels have been measured in lactating women, but the effects on milk production are not known. Breastfeeding is not recommended with maternal lithium use; however, if a woman chooses to breastfeed, the infant should be closely monitored for signs of lithium toxicity. Discontinue breastfeeding if a breastfed infant develops lithium toxicity. Clinical Considerations: Consider regular monitoring of lithium levels and thyroid function in a breastfed infant. 8.4 Pediatric Use The safety and effectiveness of lithium for monotherapy treatment of acute manic or mixed episodes of bipolar I disorder and maintenance monotherapy of bipolar I disorder in pediatric patients ages 7 to 17 years of age have been established in an acute-phase clinical trial of 8 weeks in duration followed by a 28-week randomized withdrawal phase [see Dosage and Administration ( 2.1 ), Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.3 ), Clinical Studies ( 14 )] . The safety and effectiveness of lithium has not been established in pediatric patients less than 7 years of age with bipolar I disorder. 8.5 Geriatric Use Clinical studies of lithium carbonate tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in response between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, 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 treatment. Lithium is known to be substantially excreted by the kidneys, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. 8.6 Renal Impairment As lithium is eliminated primarily through the kidney, lithium renal clearance is decreased in patients with abnormal renal function, and the risk of lithium intoxication increases considerably in this setting. Lithium should not be used in severe renal insufficiency (creatinine clearance less than 30 mL/min evaluated by Cockcroft-Gault), especially if the condition requires adherence to a low-sodium diet [see Dosage and Administration ( 2.5 )] . Start patients with mild to moderately impaired renal function (creatinine clearance 30 to 89 mL/min evaluated by Cockcroft-Gault) with lower doses of lithium and titrate slowly while frequently monitoring serum lithium concentrations and for signs of lithium toxicity [see Dosage and Administration ( 2.5 )] .

8.1 Pregnancy Risk Summary: Lithium may cause harm when administered to a pregnant woman. Early voluntary reports to international birth registries suggested an increase in cardiovascular malformations, especially for Ebstein’s anomaly, with first trimester use of lithium. Subsequent case-control and cohort studies indicate that the increased risk for cardiac malformations is likely to be small; however, the data are insufficient to establish a drug-associated risk. There are concerns for maternal and/or neonatal lithium toxicity during late pregnancy and the postpartum period [see Clinical Considerations]. Published animal developmental and toxicity studies in mice and rats report an increased incidence of fetal mortality, decreased fetal weight, increased fetal skeletal abnormalities, and cleft palate (mouse fetuses only) with oral doses of lithium that produced serum concentrations similar to the human therapeutic range. Other published animal studies report adverse effects on embryonic implantation in rats after lithium administration. Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population(s) is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations: Dose Adjustments During Pregnancy and the Postpartum Period: If the decision is made to continue lithium treatment during pregnancy, serum lithium concentrations should be monitored and the dosage adjusted during pregnancy. Two to three days prior to delivery, lithium dosage should be decreased or discontinued to reduce the risk of maternal and/or neonatal toxicity. Lithium may be restarted in the post-partum period at preconception doses in medically stable patients as long as serum lithium levels are closely monitored [see Dosage and Administration ( 2.4 ), Warnings and Precautions ( 5.1 )]. Fetal/Neonatal Adverse Reactions: Lithium toxicity may occur in neonates who were exposed to lithium in late pregnancy. A floppy baby syndrome including neurological, cardiac, and hepatic abnormalities that are similar to those seen with lithium toxicity in adults have been observed. Symptoms include hypotonia, respiratory distress syndrome, cyanosis, lethargy, feeding difficulties, depressed neonatal reflexes, neonatal depression, apnea, and bradycardia. Monitor neonates and provide supportive care until lithium is excreted and toxic signs disappear, which may take up to 14 days. Consider fetal echocardiography between 16 and 20 weeks gestation in a woman with first trimester lithium exposure because of the potential increased risk of cardiac malformations.

8.4 Pediatric Use The safety and effectiveness of lithium for monotherapy treatment of acute manic or mixed episodes of bipolar I disorder and maintenance monotherapy of bipolar I disorder in pediatric patients ages 7 to 17 years of age have been established in an acute-phase clinical trial of 8 weeks in duration followed by a 28-week randomized withdrawal phase [see Dosage and Administration ( 2.1 ), Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.3 ), Clinical Studies ( 14 )] . The safety and effectiveness of lithium has not been established in pediatric patients less than 7 years of age with bipolar I disorder.

10 OVERDOSAGE The toxic concentrations for lithium (≥ 1.5 mEq/L) are close to the therapeutic concentrations [see Warnings and Precautions ( 5.1 )]. At lithium concentrations greater than 3 mEq/L, patients may progress to seizures, coma, and irreversible brain damage. Treatment: For current information on the management of poisoning or overdosage, contact the National Poison Control Center at 1-800-222-1222 or www.poison.org . No specific antidote for lithium poisoning is known. Mild symptoms of lithium toxicity can usually be treated by reduction in dose or cessation of the drug. In severe cases of lithium poisoning, the goal of treatment is elimination of this ion from the patient. Administration of gastric lavage should be performed, but use of activated charcoal is not recommended as it does not significantly absorb lithium ions. Hemodialysis is the treatment of choice as it is an effective and rapid means of removing lithium in patients with severe toxicity. As an alternative option, urea, mannitol and aminophylline can induce a significant increase in lithium excretion. Appropriate supportive care for the patient should be undertaken. Patients with impaired consciousness should have their airway protected and it is critical to correct any volume depletion or electrolyte imbalance. Patients should be monitored to prevent hypernatremia while receiving normal saline and careful regulation of kidney function is of utmost importance. Serum lithium concentrations should be closely monitored as there may be a rebound in serum lithium concentrations as a result of delayed diffusion from the body tissues. Likewise, during the late recovery phase, lithium should be re-administered with caution taking into account the possible release of significant lithium stores in body tissues.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The mechanism of action of lithium as a mood stabilizing agent is unknown. 12.3 Pharmacokinetics Absorption: After oral administration, lithium is reported to be completely absorbed in the upper gastrointestinal tract. Peak serum concentrations (T max ) occur 0.25 to 3 hours after oral administration of immediate release preparations and 2 to 6 hours after sustained-release preparations. Distribution: The distribution space of lithium approximates that of total body water, and the plasma protein binding is negligible. After equilibrium, the apparent volume of distribution is 0.7 to 1 L/kg. Metabolism: Lithium is not metabolized. Excretion: Lithium is primarily excreted in urine, proportionally to its serum concentration. Lithium is filtered by the glomerulus, and 80% is reabsorbed by passive diffusion in the proximal tubule. The elimination half-life of lithium is approximately 18 to 36 hours. Lithium excretion in feces is insignificant. Specific Populations: Pediatric Use : A pharmacokinetic study of lithium was performed in 39 subjects with bipolar I disorder. Both apparent clearance and apparent volume of distribution increase as body weight increases. A lower dose in patients < 30 kg is necessary to achieve lithium exposures in pediatric patients similar to those observed in adults treated at recommended doses of lithium [see Dosage and Administration ( 2.2 )] . The estimated plasma clearance was 0.59 L/h, 0.79 L/h and 1.17 L/h for pediatric patients weighing 20 kg, 30 kg and 50 kg, respectively.

12.3 Pharmacokinetics Absorption: After oral administration, lithium is reported to be completely absorbed in the upper gastrointestinal tract. Peak serum concentrations (T max ) occur 0.25 to 3 hours after oral administration of immediate release preparations and 2 to 6 hours after sustained-release preparations. Distribution: The distribution space of lithium approximates that of total body water, and the plasma protein binding is negligible. After equilibrium, the apparent volume of distribution is 0.7 to 1 L/kg. Metabolism: Lithium is not metabolized. Excretion: Lithium is primarily excreted in urine, proportionally to its serum concentration. Lithium is filtered by the glomerulus, and 80% is reabsorbed by passive diffusion in the proximal tubule. The elimination half-life of lithium is approximately 18 to 36 hours. Lithium excretion in feces is insignificant. Specific Populations: Pediatric Use : A pharmacokinetic study of lithium was performed in 39 subjects with bipolar I disorder. Both apparent clearance and apparent volume of distribution increase as body weight increases. A lower dose in patients < 30 kg is necessary to achieve lithium exposures in pediatric patients similar to those observed in adults treated at recommended doses of lithium [see Dosage and Administration ( 2.2 )] . The estimated plasma clearance was 0.59 L/h, 0.79 L/h and 1.17 L/h for pediatric patients weighing 20 kg, 30 kg and 50 kg, respectively.

14 CLINICAL STUDIES The safety and efficacy of lithium as a treatment for acute manic or mixed episodes of bipolar I disorder in pediatric patients (ages 7 to ≤18 years) was demonstrated in an 8-week, randomized, placebo-controlled, parallel group study (NCT01166425). In this study, 81 patients with a Young Mania Rating Scale (YMRS) score of 20 or more were randomized to receive lithium or placebo in a 2:1 ratio. Patients weighing more than 30 kg started lithium at 300 mg three times daily (900 mg/day) and could increase their dose by 300 mg every 3 days. Patients weighing 20 to 30 kg started lithium at 300 mg twice daily (600 mg/day) and could increase their dose by 300 mg weekly. No patients weighing less than 20 kg were enrolled. Lithium (mean serum level 0.98 ± 0.47 mEq/L) was statistically significantly superior to placebo in decreasing acute mania or mixed states as measured by the YMRS (see Table 5). In a 28-week randomized withdrawal analysis, 31 pediatric patients stabilized on lithium were assigned to either continue lithium or switch to placebo. The group receiving lithium demonstrated superiority to those receiving placebo in all-cause discontinuation (see Table 5). Table 5: Primary Efficacy Results Analysis Treatment Group Change From Baseline at Week 8 in YMRS Summary Score N Mean Baseline Score (SD) LS Mean Change from Baseline (SE) Difference 1 (95% CI) Acute Efficacy Lithium: 53 29.5 (5.6) -12.9 (3.1) -5.5 (-10.5, -0.5) Placebo: 28 30 (6) -7.3 (3.1) Analysis Treatment Group 2 All-cause Discontinuation N Number of Discontinued Subjects Hazard Ratio 3 (95% CI) Randomized Withdrawal Lithium: 17 7 (41.2%) 0.28 (0.10, 0.78) Placebo: 14 11 (78.6%) SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: confidence interval. 1 Difference (drug minus placebo) in least-squares mean change from baseline. 2 Patients analyzed by received treatment. 3 Lithium to placebo.

<table width="100%"><col width="19%"/><col width="18%"/><col width="18%"/><col width="14%"/><col width="14%"/><col width="18%"/><tbody><tr><td rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph>Analysis</paragraph></td><td align="center" rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph>Treatment</paragraph><paragraph>Group</paragraph></td><td align="center" colspan="4" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph>Change From Baseline at Week 8 in YMRS Summary Score</paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>N</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Mean Baseline</paragraph><paragraph>Score (SD)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>LS Mean Change from Baseline (SE)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Difference ¹</paragraph><paragraph>(95% CI)</paragraph></td></tr><tr><td rowspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><list listType="unordered"><item>Acute Efficacy</item></list></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Lithium:</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>53</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>29.5 (5.6)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>-12.9 (3.1)</paragraph></td><td align="center" rowspan="2" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>-5.5 (-10.5, -0.5)</paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Placebo:</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>28</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>30 (6)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>-7.3 (3.1)</paragraph></td></tr><tr><td rowspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><list listType="unordered"><item>Analysis</item></list></td><td align="center" rowspan="2" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Treatment</paragraph><paragraph>Group ²</paragraph></td><td align="center" colspan="4" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>All-cause Discontinuation</paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>N</paragraph></td><td align="center" colspan="2" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Number of Discontinued Subjects</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Hazard Ratio ³</paragraph><paragraph>(95% CI)</paragraph></td></tr><tr><td rowspan="2" styleCode="Rrule Lrule Botrule " valign="middle"><list listType="unordered"><item>Randomized Withdrawal</item></list></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Lithium:</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><pa

an="2" styleCode="Rrule Lrule Botrule " valign="middle"><list listType="unordered"><item>Randomized Withdrawal</item></list></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>Lithium:</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><pa ragraph>17</paragraph></td><td align="center" colspan="2" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>7 (41.2%)</paragraph></td><td align="center" rowspan="2" styleCode="Rrule Lrule Toprule Botrule " valign="middle"><paragraph>0.28 (0.10, 0.78)</paragraph></td></tr><tr><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph>Placebo:</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph>14</paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph>11 (78.6%)</paragraph></td></tr></tbody></table>

16 HOW SUPPLIED/STORAGE AND HANDLING Lithium Carbonate Capsules, USP 600 mg supplied as hard gelatin capsules, pink cap imprinted with ‘G222’ and light gray body imprinted with ‘600’, filled with white to off-white granules. NDC: 70518-2312-00 NDC: 70518-2312-01 PACKAGING: 100 in 1 BOX PACKAGING: 70 in 1 BOX PACKAGING: 1 in 1 POUCH Storage and Dispense Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from moisture. Dispense in a tight, child-resistant container as defined in the USP/NF. Repackaged and Distributed By: Remedy Repack, Inc. 625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762

17 PATIENT COUNSELING INFORMATION Advise the patient to read FDA-approved patient labeling (Medication Guide). Dosage and Administration: Advise patients that lithium is a mood stabilizer, and should only be taken as directed. Emphasize the importance of compliance with the prescribed treatment and to not adjust the dose of lithium without first consulting their healthcare provider. Inform patients that they will need to have regular blood draws to determine if their dose of lithium is appropriate. Instruct patients not to double the dose if a dose is missed, due to the complexity of individualized dosing and potential for lithium toxicity [see Dosage and Administration ( 2 ), Warnings and Precautions ( 5.1 )]. Lithium Toxicity: Inform patients on adverse reactions related to lithium toxicity that require medical attention. Advise patients to discontinue lithium treatment and contact their healthcare provider if clinical signs of lithium toxicity such as diarrhea, vomiting, tremor, lack of muscle coordination, drowsiness, abnormal heart rhythm or muscular weakness occur [see Warnings and Precautions ( 5.1 )] . Lithium-Induced Polyuria: Counsel patients on the adverse reactions related to lithium-induced polyuria, when to seek medical attention, and the importance of maintaining normal diet with salt and staying hydrated [see Warnings and Precautions ( 5.2 )] . Hyponatremia: Counsel patients on the adverse reactions of hyponatremia, when to seek medical attention, the importance of maintaining a normal diet including adequate salt intake and staying hydrated [see Warnings and Precautions ( 5.3 )] . Salt supplements and additional fluids may be required if excessive losses occur. Serotonin Syndrome: Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of lithium with other serotonergic drugs including SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, tramadol, tryptophan, buspirone, 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) [see Warnings and Precautions ( 5.6 ) and Drug Interactions ( 7 )] . Drug Interactions: Advise patients that many drugs can interact with lithium and to inform their doctor and pharmacist if they are taking any over the counter medication, including herbal medication, or are started on a new prescription [see Drug Interactions ( 7 )] . Somnolence: Tell patients that lithium may cause somnolence particularly when initiating treatment and to be cautious about operating vehicles or hazardous machinery, until they are reasonably certain that lithium treatment does not affect them adversely [see Adverse Reactions ( 6 )] . Pregnancy: Advise pregnant women of the potential risk to a fetus and/or neonate [see Use in Specific Populations ( 8.1 )] . Lactation: Advise women that breastfeeding is not recommended during treatment with lithium [see Use in Specific Populations ( 8.2 )] . Medication Guide available at www.glenmarkpharma-us.com/medguides Repackaged By / Distributed By: RemedyRepack Inc. 625 Kolter Drive, Indiana, PA 15701 (724) 465-8762

MEDICATION GUIDE Lithium ( LITH-ee-əm ) Carbonate capsules, USP What is the most important information I should know about lithium carbonate capsules? Lithium carbonate capsules can cause serious side effects, including: too much lithium in your blood (lithium toxicity). Lithium toxicity that can cause death may happen even if the lithium level in your blood is close to the right level for you. Your healthcare provider will need to monitor your blood levels of lithium to find the best dose for you. Take your lithium carbonate capsules exactly as your healthcare provider tells you to take it. Stop taking lithium carbonate capsules and call your healthcare provider right away if you have any symptoms of lithium toxicity including: abnormal heartbeat vomiting diarrhea drowsiness weak muscles blurred vision clumsiness ringing in your ears muscle twitching Other symptoms may include: lightheadedness confusion bloating mood changes slurred speech breathing problems seizure coma What are lithium carbonate capsules? Lithium carbonate capsules are prescription medicines called mood-stabilizing agents used alone (monotherapy) for: the acute (short-term) treatment of people 7 years of age and older with manic and mixed episodes that happen with bipolar I disorder. maintenance treatment of bipolar I disorder in people 7 years of age and older. It is not known if lithium carbonate capsules are safe and effective in children under 7 years of age with bipolar I disorder. Who should not take lithium carbonate capsules? Do not take lithium carbonate capsules if you are allergic to lithium or any of the ingredients in lithium carbonate capsules. See the end of this Medication Guide for a complete list of ingredients in lithium carbonate capsules. What should I tell my healthcare provider before taking lithium carbonate capsules? Before taking lithium carbonate capsules, tell your healthcare provider if you: have kidney problems have heart problems have breathing problems have thyroid problems are pregnant or plan to become pregnant. Lithium carbonate may harm your unborn baby. are breastfeeding or plan to breastfeed. Lithium carbonate can pass into your breastmilk and may harm your baby. You should not breastfeed during treatment with lithium carbonate capsules. Talk to your healthcare provider about the best way to feed your baby if you take lithium carbonate capsules. Tell your healthcare provider about all the medicines you take, including prescription, over-the-counter medicines, vitamins, and herbal supplements. Using lithium carbonate capsules with certain other medicines may affect each other causing possible side effects. Lithium carbonate capsules may affect the way other medicines work, and other medicines may affect how lithium carbonate capsules works. Especially tell your healthcare provider if you take: MAOIs selective serotonin reuptake inhibitors (SSRIs) serotonin norepinephrine reuptake inhibitors (SNRIs) medicines used to treat migraine headaches called triptans tricyclic antidepressants fentanyl antipsychotic medicines tramadol tryptophan buspirone St John’s Wort Your healthcare provider can tell you if it is safe to take lithium carbonate capsules with your other medicines. Do not start or stop any medicines while taking lithium carbonate capsules without talking to your healthcare provider first. Know the medicines you take. Keep a list of your medicines to show your healthcare provider and pharmacist when you get a new medicine.

take lithium carbonate capsules with your other medicines. Do not start or stop any medicines while taking lithium carbonate capsules without talking to your healthcare provider first. Know the medicines you take. Keep a list of your medicines to show your healthcare provider and pharmacist when you get a new medicine. How should I take lithium carbonate capsules? Take your lithium carbonate capsules exactly as prescribed by your healthcare provider. Your healthcare provider will do certain blood tests before starting and during treatment with lithium carbonate capsules. Your healthcare provider may change your dose if needed. Do not change your dose on your own. Do not double your dose if a dose is missed. Talk with your healthcare provider if you miss a dose. Do not stop taking lithium carbonate capsules suddenly without talking to your healthcare provider. Your healthcare provider may change your lithium carbonate capsules dose to make sure you are taking the dose that is right for you. If you take too much lithium carbonate capsules, call your healthcare provider or poison control center, or go to the nearest hospital emergency room right away. In case of poisoning, call your poison control center at 1-800-222-1222. What should I avoid while taking lithium carbonate capsules? Do not drive, operate heavy machinery, or do other dangerous activities when you start taking lithium carbonate capsules, when your dose is changed, or until you know how lithium carbonate capsules affects you. Lithium carbonate capsules can make you sleepy. Talk to your healthcare provider about these activities. Avoid becoming overheated or dehydrated during exercise and in hot weather. Follow your healthcare provider instructions about the type and amount of liquids you should drink. In some cases, drinking too much liquid can be as unsafe as not drinking enough. Do not change the amount of salt in your diet. Changing the amount of salt in your diet could change the amount of lithium carbonate in your blood. What are the possible side effects of lithium carbonate capsules? See “What is the most important information I should know about lithium carbonate capsules? Lithium carbonate capsules may cause serious side effects, including: kidney problems. People who take lithium carbonate capsules may have to urinate often (polyuria) and have other kidney problems that may affect how their kidneys work. These problems can happen within a few weeks of starting to take lithium carbonate capsules or after taking lithium carbonate capsules for a long time. low levels of sodium (salt) in your blood (hyponatremia). Lithium carbonate capsules can cause you to lose sodium. Talk to your healthcare provider about your diet and how much fluid you are drinking when starting lithium carbonate capsules. If you have been sweating more than usual or have had diarrhea, you may need extra salt and more fluids. Talk to your healthcare provider if this happens. neurological problems. People who take lithium carbonate capsules with certain other medicines called antipsychotics may have symptoms such as weakness, tiredness, fever, tremors, and confusion. Talk to your healthcare provider if this happens. Ask if you are not sure about the medicines you take. serotonin syndrome. A potentially life-threatening problem called serotonin syndrome can happen when you take lithium carbonate capsules while you take certain medicines called serotonergic and MAOIs. Symptoms of serotonin syndrome include: thyroid problems. high calcium levels in your blood (hypercalcemia) and changes in your parathyroid gland (hyperparathyroidism) that may not go away when you stop taking lithium carbonate capsules. heart problems.

es while you take certain medicines called serotonergic and MAOIs. Symptoms of serotonin syndrome include: thyroid problems. high calcium levels in your blood (hypercalcemia) and changes in your parathyroid gland (hyperparathyroidism) that may not go away when you stop taking lithium carbonate capsules. heart problems. People who take lithium carbonate capsules may find out they also have a heart problem called Brugada Syndrome. People who have unexplained fainting or who have a family history of sudden unexplained death before 45 years of age may have Brugada Syndrome and not know it. If you faint or feel abnormal heartbeats, talk to your healthcare provider right away. increased pressure in the brain and swelling in the eye (pseudotumor cerebri) that can cause vision problems or blindness. If you have severe headaches behind your eyes, ringing in the ears, blurred vision, double vision, or brief periods of blindness, talk to your health care provider right away. The most common side effects of lithium carbonate capsules include: Adults with manic or mixed episodes of bipolar I disorder: hand trembling excessive urination increased thirst nausea general discomfort when you start treatment Children 7 to 17 years of age with manic or mixed episodes of bipolar I disorder: excessive urination` thyroid problems hand trembling excessive thirst dizziness rash difficulty walking decreased appetite blurred vision nausea vomiting These are not all the possible side effects of lithium carbonate capsules. 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 lithium carbonate capsules? Store lithium carbonate capsules at room temperature, between 68°F to 77°F (20°C to 25°C). Keep capsules dry and keep in a tightly closed container. Keep lithium carbonate capsules, and all medicines out of the reach of children. General information about the safe and effective use of lithium carbonate capsules. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use lithium carbonate capsules for a condition for which it was not prescribed. Do not give lithium carbonate capsules to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about lithium carbonate capsules that is written for healthcare professionals. For more information about lithium carbonate capsules, call Glenmark Pharmaceuticals Inc., USA at 1 (888) 721-7115. What are the ingredients in lithium carbonate capsules? Active ingredient: lithium carbonate, USP Inactive ingredients: colloidal silicon dioxide, gelatin, sodium lauryl sulfate, talc, titanium dioxide, FD&C Blue No. 1, FD&C Red No. 40, D&C Yellow No. 10 and the imprinting ink contains shellac, propylene glycol, potassium hydroxide, and black iron oxide. Medication Guide available at www.glenmarkpharma-us.com/medguides This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: July 2025 Repackaged By / Distributed By: RemedyRepack Inc. 625 Kolter Drive, Indiana, PA 15701 (724) 465-8762

<table width="100%"><colgroup><col width="100%"/></colgroup><tbody><tr><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Lithium ( <content styleCode="underline">LITH-ee-&#x259;m</content>) Carbonate </content></paragraph><paragraph><content styleCode="bold">capsules, USP</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">What is the most important information I should know about lithium carbonate capsules?</content></paragraph><paragraph><content styleCode="bold">Lithium carbonate capsules can cause serious side effects, including:</content></paragraph><list listType="unordered"><item><content styleCode="bold">too much lithium in your blood (lithium toxicity).</content>Lithium toxicity that can cause death may happen even if the lithium level in your blood is close to the right level for you. Your healthcare provider will need to monitor your blood levels of lithium to find the best dose for you. Take your lithium carbonate capsules exactly as your healthcare provider tells you to take it. <content styleCode="bold">Stop taking lithium carbonate capsules and call your healthcare provider right away if you have any symptoms of lithium toxicity including:</content></item><item>abnormal heartbeat</item><item>vomiting</item><item>diarrhea</item><item>drowsiness</item><item>weak muscles</item><item>blurred vision</item><item>clumsiness</item><item>ringing in your ears</item><item>muscle twitching</item><item><content styleCode="bold">Other symptoms may include:</content></item><item>lightheadedness</item><item>confusion</item><item>bloating</item><item>mood changes</item><item>slurred speech</item><item>breathing problems</item><item>seizure</item><item>coma</item></list></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">What are lithium carbonate capsules?</content></paragraph><paragraph>Lithium carbonate capsules are prescription medicines called mood-stabilizing agents used alone (monotherapy) for:</paragraph><list listType="unordered"><item>the acute (short-term) treatment of people 7 years of age and older with manic and mixed episodes that happen with bipolar I disorder.</item><item>maintenance treatment of bipolar I disorder in people 7 years of age and older.</item></list><paragraph>It is not known if lithium carbonate capsules are safe and effective in children under 7 years of age with bipolar I disorder.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Who should not take lithium carbonate capsules?</content></paragraph><paragraph><content styleCode="bold">Do not take lithium carbonate capsules</content>if you are allergic to lithium or any of the ingredients in lithium carbonate capsules. See the end of this Medication Guide for a complete list of ingredients in lithium carbonate capsules.

ium carbonate capsules?</content></paragraph><paragraph><content styleCode="bold">Do not take lithium carbonate capsules</content>if you are allergic to lithium or any of the ingredients in lithium carbonate capsules. See the end of this Medication Guide for a complete list of ingredients in lithium carbonate capsules. </paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">What should I tell my healthcare provider before taking lithium carbonate capsules?</content></paragraph><paragraph>Before taking lithium carbonate capsules, tell your healthcare provider if you:</paragraph><list listType="unordered"><item>have kidney problems</item><item>have heart problems</item><item>have breathing problems</item><item>have thyroid problems</item><item>are pregnant or plan to become pregnant. Lithium carbonate may harm your unborn baby.</item><item>are breastfeeding or plan to breastfeed. Lithium carbonate can pass into your breastmilk and may harm your baby. You should not breastfeed during treatment with lithium carbonate capsules. Talk to your healthcare provider about the best way to feed your baby if you take lithium carbonate capsules.</item></list><paragraph><content styleCode="bold">Tell your healthcare provider about all the medicines you take,</content>including prescription, over-the-counter medicines, vitamins, and herbal supplements. </paragraph><paragraph>Using lithium carbonate capsules with certain other medicines may affect each other causing possible side effects. Lithium carbonate capsules may affect the way other medicines work, and other medicines may affect how lithium carbonate capsules works.</paragraph><paragraph><content styleCode="bold">Especially tell your healthcare provider if you take:</content></paragraph><list listType="unordered"><item>MAOIs</item><item>selective serotonin reuptake inhibitors (SSRIs)</item><item>serotonin norepinephrine reuptake inhibitors (SNRIs)</item><item>medicines used to treat migraine headaches called triptans</item><item>tricyclic antidepressants</item><item>fentanyl</item><item>antipsychotic medicines</item><item>tramadol</item><item>tryptophan</item><item>buspirone</item><item>St John&#x2019;s Wort</item></list><paragraph>Your healthcare provider can tell you if it is safe to take lithium carbonate capsules with your other medicines. <content styleCode="bold">Do not</content>start or stop any medicines while taking lithium carbonate capsules without talking to your healthcare provider first. </paragraph><paragraph>Know the medicines you take. Keep a list of your medicines to show your healthcare provider and pharmacist when you get a new medicine.</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">How should I take lithium carbonate capsules?</content></paragraph><list listType="unordered"><item>Take your lithium carbonate capsules exactly as prescribed by your healthcare provider.</item><item>Your healthcare provider will do certain blood tests before starting and during treatment with lithium carbonate capsules.</item><item>Your healthcare provider may change your dose if needed. <content styleCode="bold">Do not</content>change your dose on your own. </item><item><content styleCode="bold">Do not</content>double your dose if a dose is missed. Talk with your healthcare provider if you miss a dose. </item><item><content styleCode="bold">Do not</content>stop taking lithium carbonate capsules suddenly without talking to your healthcare provider.

e your dose on your own. </item><item><content styleCode="bold">Do not</content>double your dose if a dose is missed. Talk with your healthcare provider if you miss a dose. </item><item><content styleCode="bold">Do not</content>stop taking lithium carbonate capsules suddenly without talking to your healthcare provider. </item><item>Your healthcare provider may change your lithium carbonate capsules dose to make sure you are taking the dose that is right for you.</item><item>If you take too much lithium carbonate capsules, call your healthcare provider or poison control center, or go to the nearest hospital emergency room right away. In case of poisoning, call your poison control center at 1-800-222-1222.</item></list></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">What should I avoid while taking lithium carbonate capsules?</content></paragraph><list listType="unordered"><item><content styleCode="bold">Do not</content>drive, operate heavy machinery, or do other dangerous activities when you start taking lithium carbonate capsules, when your dose is changed, or until you know how lithium carbonate capsules affects you. Lithium carbonate capsules can make you sleepy. Talk to your healthcare provider about these activities. </item><item>Avoid becoming overheated or dehydrated during exercise and in hot weather. Follow your healthcare provider instructions about the type and amount of liquids you should drink. In some cases, drinking too much liquid can be as unsafe as not drinking enough.</item><item><content styleCode="bold">Do not</content>change the amount of salt in your diet. Changing the amount of salt in your diet could change the amount of lithium carbonate in your blood. </item></list></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">What are the possible side effects of lithium carbonate capsules?</content></paragraph><paragraph><content styleCode="bold">See &#x201C;What is the most important information I should know about lithium carbonate capsules?</content></paragraph><paragraph><content styleCode="bold">Lithium carbonate capsules may cause serious side effects, including:</content></paragraph><list listType="unordered"><item><content styleCode="bold">kidney problems.</content>People who take lithium carbonate capsules may have to urinate often (polyuria) and have other kidney problems that may affect how their kidneys work. These problems can happen within a few weeks of starting to take lithium carbonate capsules or after taking lithium carbonate capsules for a long time. </item><item><content styleCode="bold">low levels of sodium (salt) in your blood (hyponatremia).</content>Lithium carbonate capsules can cause you to lose sodium. Talk to your healthcare provider about your diet and how much fluid you are drinking when starting lithium carbonate capsules. If you have been sweating more than usual or have had diarrhea, you may need extra salt and more fluids. Talk to your healthcare provider if this happens. </item><item><content styleCode="bold">neurological problems.</content>People who take lithium carbonate capsules with certain other medicines called antipsychotics may have symptoms such as weakness, tiredness, fever, tremors, and confusion. Talk to your healthcare provider if this happens. Ask if you are not sure about the medicines you take. </item><item><content styleCode="bold">serotonin syndrome.</content>A potentially life-threatening problem called serotonin syndrome can happen when you take lithium carbonate capsules while you take certain medicines called serotonergic and MAOIs.

if this happens. Ask if you are not sure about the medicines you take. </item><item><content styleCode="bold">serotonin syndrome.</content>A potentially life-threatening problem called serotonin syndrome can happen when you take lithium carbonate capsules while you take certain medicines called serotonergic and MAOIs. Symptoms of serotonin syndrome include: </item></list><list listType="unordered"><item><content styleCode="bold">thyroid problems.</content></item><item><content styleCode="bold">high calcium levels in your blood (hypercalcemia) and changes in your parathyroid gland (hyperparathyroidism)</content>that may not go away when you stop taking lithium carbonate capsules. </item><item><content styleCode="bold">heart problems.</content>People who take lithium carbonate capsules may find out they also have a heart problem called Brugada Syndrome. People who have unexplained fainting or who have a family history of sudden unexplained death before 45 years of age may have Brugada Syndrome and not know it. If you faint or feel abnormal heartbeats, talk to your healthcare provider right away. </item><item><content styleCode="bold">increased pressure in the brain and swelling in the eye (pseudotumor cerebri)</content>that can cause vision problems or blindness. If you have severe headaches behind your eyes, ringing in the ears, blurred vision, double vision, or brief periods of blindness, talk to your health care provider right away. </item></list><paragraph>The most common side effects of lithium carbonate capsules include:</paragraph><list listType="unordered"><item>Adults with manic or mixed episodes of bipolar I disorder: <list listType="unordered"><item>hand trembling</item><item>excessive urination</item><item>increased thirst</item><item>nausea</item><item>general discomfort when you start treatment</item></list></item><item>Children 7 to 17 years of age with manic or mixed episodes of bipolar I disorder: <list listType="unordered"><item>excessive urination`</item><item>thyroid problems</item><item>hand trembling</item><item>excessive thirst</item><item>dizziness</item><item>rash</item><item>difficulty walking</item><item>decreased appetite</item><item>blurred vision</item><item>nausea</item><item>vomiting</item></list></item></list><paragraph>These are not all the possible side effects of lithium carbonate capsules.</paragraph><list listType="unordered"><item>Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</item></list></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">How should I store lithium carbonate capsules?</content></paragraph><paragraph>Store lithium carbonate capsules at room temperature, between 68&#xB0;F to 77&#xB0;F (20&#xB0;C to 25&#xB0;C).</paragraph><paragraph>Keep capsules dry and keep in a tightly closed container.</paragraph><paragraph><content styleCode="bold">Keep lithium carbonate capsules, and all medicines out of the reach of children.</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">General information about the safe and effective use of lithium carbonate capsules.</content></paragraph><paragraph>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use lithium carbonate capsules for a condition for which it was not prescribed. Do not give lithium carbonate capsules to other people, even if they have the same symptoms you have. It may harm them.

ragraph><paragraph>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use lithium carbonate capsules for a condition for which it was not prescribed. Do not give lithium carbonate capsules to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about lithium carbonate capsules that is written for healthcare professionals.</paragraph><list listType="unordered"><item>For more information about lithium carbonate capsules, call Glenmark Pharmaceuticals Inc., USA at 1 (888) 721-7115.</item></list></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="top"><paragraph><content styleCode="bold">What are the ingredients in lithium carbonate capsules?</content></paragraph><paragraph><content styleCode="bold">Active ingredient:</content>lithium carbonate, USP </paragraph><paragraph><content styleCode="bold">Inactive ingredients:</content></paragraph><paragraph>colloidal silicon dioxide, gelatin, sodium lauryl sulfate, talc, titanium dioxide, FD&amp;C Blue No. 1, FD&amp;C Red No. 40, D&amp;C Yellow No. 10 and the imprinting ink contains shellac, propylene glycol, potassium hydroxide, and black iron oxide.</paragraph></td></tr></tbody></table>