spironolactone and trimethoprim

Both spironolactone and trimethoprim reduce renal potassium excretion. Spironolactone blocks aldosterone receptors in the distal tubule. Trimethoprim inhibits the epithelial sodium channel in the collecting duct. Their effects are additive, increasing serum potassium.

Combining these drugs can cause clinically significant hyperkalaemia, which may lead to cardiac arrhythmias including ventricular fibrillation and cardiac arrest. Risk is higher in patients with pre-existing renal impairment, diabetes, or taking other potassium-raising drugs.

Avoid co-prescription if possible. If the combination is necessary, monitor serum potassium and renal function at baseline and within 5 to 7 days after starting therapy, and periodically thereafter. Advise patients to avoid potassium supplements and salt substitutes. Consider alternative antibiotics without potassium-sparing effects.

This interaction is well documented in clinical case reports and small studies. The additive effect on serum potassium is consistently reported. National formularies and guidelines advise caution or avoidance.