FDA

Lithium Carbonate

Approved 5 Jun 2017OralTablet, extended release

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 Carbonate Extended-Release Tablets is 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 and precautions

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 ]. 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:

At a glance

Brand name: Lithium Carbonate
Route: Oral
Dosage form: Tablet, extended release
Applicant: Unique
Status: Prescription
FDA approval: 5 Jun 2017
Application: ANDA205663-001

Indications

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 and precautions

The risk of lithium toxicity is increased by:

Interactions

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 angiotensin 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 ).

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 2.0 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 2.0 mEq/L. At higher levels, ataxia, giddiness, tinnitus, blurred vision, and a large output of dilute urine may be seen. Serum lithium levels above 3.0 mEq/L may produce a complex clinical picture, involving multiple organs and organ systems. Serum lithium levels should not be permitted to exceed 2.0 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. 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.

Lithium Carbonate

Indications

Warnings and precautions

At a glance

Two medicines in one question?

Lithium Carbonate

Indications

Warnings and precautions

At a glance

Two medicines in one question?

Interactions

Adverse reactions

Composition

Strengths and forms

Official product information