WARNINGS

Lithium Toxicity Lithium toxicity is closely related to serum lithium levels, and can occur at doses close to therapeutic levels (see DOSAGE AND ADMINISTRATION).

Outpatients and their families should be warned that the patient must discontinue lithium carbonate therapy and contact his physician if such clinical signs of lithium toxicity as diarrhea, vomiting, tremor, mild ataxia, drowsiness or muscular weakness occur.

Lithium carbonate may impair mental and/or physical abilities.

Caution patients about activities requiring alertness (e.g., operating vehicles or machinery).

Lithium should generally not be given to patients with significant renal or cardiovascular disease, severe debilitation or dehydration, or sodium depletion, since the risk of lithium toxicity is very high in such patients.

If the psychiatric indication is life-threatening, and if such a patient fails to respond to other measures, lithium treatment may be undertaken with extreme caution, including daily serum lithium determinations and adjustment to the usually low doses ordinarily tolerated by these individuals.

In such instances, hospitalization is a necessity.

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.

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.

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.

When kidney function is assessed, for baseline data prior to starting lithium therapy or thereafter, 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 or creatinine clearance).

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).

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 Teratogenic Effects 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 child.

Usage in Pediatric Patients Since information regarding the safety and effectiveness of lithium carbonate in children under 12 years of age is not available, its use in such 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 the Elderly Elderly patients often require lower lithium dosages to achieve therapeutic serum levels.

They may also exhibit adverse reactions at serum levels ordinarily tolerated by younger patients.