FDA

Lithium Carbonate

Approved 12 Jan 2009OralCapsule

The FDA lists this product in 40 strengths and forms.

Boxed warningThe FDA label of this medicine carries a boxed warning, the strongest warning the FDA gives. Read it under warnings and precautions.

Indications

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)

Contraindications

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

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).

At a glance

Brand name: Lithium Carbonate
Route: Oral
Dosage form: Capsule
Applicant: Alembic LTD
Status: Prescription
FDA approval: 12 Jan 2009
Application: ANDA079159-003
RxCUI: 42351

Indications

Warnings and precautions

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.

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.

Pregnancy and breastfeeding

8.1Pregnancy 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.

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 Alembic Pharmaceuticals Limited at 1-866-210-9797 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1Clinical 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.

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.

Lithium Carbonate

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Lithium Carbonate

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

5.1Lithium Toxicity

5.2Lithium-Induced Polyuria

5.3Hyponatremia

5.4Lithium-Induced Chronic Kidney Disease

5.5Encephalopathic Syndrome

Interactions

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary:

Adverse reactions

6.1Clinical Trials Experience

Composition

Strengths and forms

Official product information