lisinopril and trimethoprim

Additive pharmacodynamic effect on potassium homeostasis. Lisinopril inhibits ACE, reducing aldosterone production and thereby decreasing renal potassium excretion. Trimethoprim blocks epithelial sodium channels (ENaC) in the distal nephron, which also reduces potassium secretion. Both drugs can independently reduce glomerular filtration rate, further contributing to potassium retention.

Co-administration can lead to clinically significant hyperkalaemia, especially in patients with pre-existing renal impairment, diabetes, heart failure, or those receiving other potassium-elevating agents (e.g. potassium-sparing diuretics, NSAIDs). Mild hyperkalaemia may be asymptomatic, but severe elevations can cause muscle weakness, cardiac arrhythmias, and cardiac arrest.

Avoid empiric combination in high-risk patients. If co-prescription is necessary, check baseline serum potassium and renal function, recheck within 1–2 weeks after starting therapy, and periodically thereafter. Advise patients to avoid potassium supplements and salt substitutes. If hyperkalaemia develops, stop the offending drug(s), treat accordingly, and consider switching trimethoprim to an alternative antibiotic (e.g. nitrofurantoin for uncomplicated UTI) where clinically appropriate.

Well-established interaction. Numerous case reports and cohort studies document hyperkalaemia with this combination. Guidelines and product information recommend monitoring potassium levels. The risk is highest in patients with chronic kidney disease or diabetes.