Lithium Carbonate

May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

In a scientific statement from the American Heart Association, lithium has been determined to be an agent that may cause direct myocardial toxicity that is reversible upon discontinuation (magnitude: major) (AHA [Page 2016]).

Hypercalcemia with or without hyperparathyroidism has been reported. Risks are greater in women and possibly in older patients; symptom onset does not appear to be related to therapy duration (Lehmann 2013). Serum calcium levels typically range from slightly above normal to over 15 mg/dL and PTH levels may range from high normal to several times the upper limit of normal (Lehmann 2013); magnesium levels are often elevated; serum phosphate levels may be either normal or low (Grandjean 2009). Monitor calcium and PTH levels as clinically indicated. Consider discontinuation if clinical manifestations of hypercalcemia are present (fatigue, weakness, abdominal pain, constipation, nephrolithiasis, bone pain) or if calcium levels are >11.4 mg/dL. Following discontinuation, check serum calcium levels weekly for one month for return to baseline. Changes are usually reversible if lithium is discontinued; however, sustained hypercalcemia and parathyroid gland enlargement has been reported (Lehmann 2013).

May cause hypothyroidism, generally within 6 to 18 months of initiating treatment. Women may be at an increased risk. If hypothyroidism develops and symptoms of bipolar disorder are well-controlled, consider continuing lithium and treating hypothyroidism (APA 2002).

Chronic therapy results in diminished renal concentrating ability (nephrogenic diabetes insipidus); this is usually reversible when lithium is discontinued. Monitor for changes in renal function and avoid dehydration; re-evaluation of treatment may be necessary. Morphologic changes with glomerular and interstitial fibrosis and nephron atrophy have been reported in patients on chronic lithium therapy; morphologic changes have also been reported in patients with bipolar disorder never exposed to lithium. The relationship between morphologic changes and renal function, and the association with lithium therapy, have not been established. If polyuria develops during lithium therapy, consolidating to once-daily dosing may decrease urine output (APA 2002; Carter 2013). Disease-related concerns:

Generally avoid use in patients with significant cardiovascular disease due to an increased risk of lithium toxicity; if use is unavoidable, use with extreme caution and monitor serum lithium levels closely. Lithium may unmask Brugada syndrome; avoid use in patients with or suspected of having Brugada syndrome. Consult with a cardiologist if a patient is suspected of having Brugada syndrome or has risk factors for Brugada syndrome (eg, unexplained syncope, a family history of Brugada syndrome, a family history of sudden death before the age of 45 years), or if unexplained syncope or palpitations develop after starting therapy.

Generally avoid use in patients with significant fluid loss or sodium depletion due to an increased risk of lithium toxicity. If use is unavoidable, use extreme caution and monitor serum lithium levels closely. Decreased tolerance to lithium has been reported with 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 therapy.

Use with caution in patients at risk of suicide (suicidal thoughts or behavior) by drug overdose; lithium has a narrow therapeutic index (APA 2002).

Generally avoid use in patients with significant renal disease due to an increased risk of lithium toxicity. If use is unavoidable, use extreme caution and monitor serum lithium levels closely.

Use with caution in patients with thyroid disease; hypothyroidism may occur with treatment (APA 2002). Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Generally avoid use in severely debilitated patients due to an increased risk of lithium toxicity; if use is unavoidable, use extreme caution and monitor serum lithium levels closely.

Use with caution in the elderly patients due to an increased risk of lithium toxicity. Dosage form specific issues:

Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.

Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer’s labeling. Other warnings/precautions:

Higher serum concentrations may be required and tolerated during an acute manic phase; however, the tolerance decreases when symptoms subside.

Lithium toxicity is closely related to serum concentrations and can occur at doses close to therapeutic levels. Facilities for prompt and accurate serum lithium determinations should be available before initiating therapy. Normal fluid and salt intake must be maintained during therapy. Lithium should generally not be given to patients with significant renal or cardiovascular disease, severe debilitation or dehydration, or sodium depletion due to risk of lithium toxicity; if use is unavoidable, lithium may be undertaken with extreme caution, including frequent serum lithium determinations and possibly hospitalization. Discontinue therapy if such clinical signs of lithium toxicity occur (eg, diarrhea, vomiting, tremor, mild ataxia, drowsiness, or muscular weakness).