lithium and bendroflumethiazide

Thiazide diuretics such as bendroflumethiazide reduce the renal clearance of lithium. They cause sodium and water depletion, which increases proximal tubular reabsorption of lithium and sodium. This leads to elevated plasma lithium concentrations, potentially to toxic levels. The effect is generally seen within days to weeks of starting the diuretic.

Increased lithium levels can cause lithium toxicity, presenting with nausea, vomiting, diarrhoea, tremor, ataxia, confusion, seizures, and in severe cases coma and death. The onset is often gradual, and symptoms may occur even at therapeutic doses if levels rise too high. Toxicity is more likely if dehydration or renal impairment is also present.

Avoid this combination if possible. If co-prescription is necessary, monitor serum lithium levels frequently, for example every 3 to 5 days initially and then weekly until stable. Reduce the lithium dose as needed and monitor for signs of toxicity, including neurological and gastrointestinal symptoms. Advise the patient to maintain adequate fluid intake and to seek medical attention if symptoms develop. Consider alternative diuretics, such as loop diuretics, which have a smaller effect on lithium clearance, but regular monitoring is still advised.

Well established in clinical practice and supported by numerous case reports and clinical studies. This interaction is listed in major drug interaction compendia and national guidelines, including the British National Formulary (BNF) and NICE guidance, which recommend caution and monitoring when a thiazide diuretic is used with lithium.