Lithium - Warnings and Precautions

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: 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, 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.

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.