Major
Co-trimoxazole × Spironolactone
Sulfonamide-trimethoprim combination×Potassium-sparing diuretics (mineralocorticoid receptor antagonists)
Mechanism
Trimethoprim in co-trimoxazole blocks epithelial sodium channels in renal collecting ducts via the same mechanism as amiloride. Combined with spironolactone this produces dual potassium retention. In the elderly and in chronic kidney disease cohort studies show increased sudden death rates with the combination.
Symptoms
Hyperkalaemia within 1–2 weeks: weakness, paresthesia, arrhythmia. Detected on labs; symptoms appear late.
Management
Switch to an alternative antibiotic when possible (amoxicillin, cefalexin for urinary tract infection). If co-trimoxazole is required, check potassium and creatinine on days 3–5 and at end of course. Avoid the combination in patients over 65 with eGFR below 60 mL/min/1.73 m².
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.