Drug Interactions between hydrochlorothiazide / olmesartan and lithium

GENERALLY AVOID: Thiazide diuretics may cause a rapid increase in serum lithium levels and potentiate the risk of lithium toxicity. The exact mechanism is unknown but may be related to the sodium loss induced by thiazide diuresis, which produces a compensatory increase in proximal tubular reabsorption of sodium along with lithium. In a study of 22 patients receiving bendroflumethiazide 2.5 mg or hydroflumethiazide 25 mg daily for the treatment of edema, mean renal clearance of a single 600 mg dose of lithium carbonate was reduced by 24% during thiazide diuretic therapy compared to before or after diuretic therapy. A similar reduction in renal lithium clearance has been reported in studies with chlorothiazide. There have also been case reports of patients developing lithium toxicity shortly after initiation of various thiazide diuretics including bendroflumethiazide, chlorothiazide, chlorthalidone, hydrochlorothiazide and indapamide, either alone or in combination with other diuretics. Up to severalfold increases in serum lithium levels have been observed, usually within several days to 2 weeks but occasionally longer. The risk for lithium toxicity may be further increased during concomitant sodium restriction.

MANAGEMENT: Thiazide diuretics should generally not be prescribed to patients receiving lithium unless close monitoring of serum lithium levels and electrolytes can be rendered. Lithium dose reductions may be required. Patients should be advised to notify their physician if they experience potential signs and symptoms of lithium toxicity such as drowsiness, dizziness, muscle weakness, vomiting, diarrhea, thirst, polyuria, tinnitus, tremor, ataxia, and blurred vision. Some investigators have suggested that loop diuretics are safer with lithium than thiazide diuretics, although supporting data are limited.

MONITOR CLOSELY: Concomitant use of angiotensin II receptor antagonists (ARBs) may increase the serum concentrations of lithium. The exact mechanism of the interaction is unknown, but may be related to the blockade of angiotensin II type 1 receptor by the ARB causing decreased sodium reabsorption (natriuresis) and increased lithium reabsorption in the proximal convoluted tubule (PCT). Increased steady-state lithium concentrations and lithium toxicity, including death, have been described in multiple case reports with various ARBs in association with the interaction, sometimes with a delayed onset of up to several weeks after coadministration.

MANAGEMENT: Given the narrow therapeutic index of lithium, caution is advised during coadministration with angiotensin II receptor antagonists, particularly in the elderly or patients with other risk factors (e.g., sodium restriction, renal impairment, congestive heart failure, dehydration, concomitant use of diuretics or NSAIDs). The labeling for some ARBs recommends avoiding this combination, while the labeling of others suggest they may be coadministered if necessary, but with additional monitoring. If coadministration is necessary, lithium product labeling recommends more frequent monitoring of serum lithium levels and renal function, as well as possible lithium dose reductions. Patients and their caregivers should be advised to seek medical attention if they experience potential signs and symptoms of lithium toxicity (e.g., drowsiness, dizziness, confusion, muscle weakness, vomiting, diarrhea, polydipsia, polyuria, tinnitus, tremor, ataxia, and blurred vision). Individual product labeling should be consulted for further guidance.