lithium and hydrochlorothiazide

Hydrochlorothiazide decreases the renal clearance of lithium by increasing sodium reabsorption in the proximal tubule, which enhances lithium reabsorption. This results in elevated serum lithium concentrations.

Co-administration can lead to lithium toxicity, with symptoms such as nausea, vomiting, tremor, ataxia, confusion, and in severe cases seizures or coma. Toxicity may develop even at therapeutic lithium doses.

Avoid the combination if possible. If unavoidable, reduce the lithium dose and monitor serum lithium levels closely, especially after starting or stopping the thiazide. Consider using an alternative diuretic that has less effect on lithium clearance.

This interaction is well established in clinical practice and supported by numerous case reports and pharmacokinetic studies. It is consistently listed in major drug interaction references.