Major
Co-trimoxazole × Spironolactone
Sulfonamide-trimethoprim combination×Potassium-sparing diuretics (mineralocorticoid receptor antagonists)
Mechanism
Trimethoprim in co-trimoxazole blocks collecting duct sodium channels via an amiloride-like mechanism, additively with spironolactone causing severe hyperkalaemia. Antoniou 2014 showed increased sudden cardiac death risk.
Symptoms
Muscle weakness, paraesthesia, slowed pulse, arrhythmias. ECG: peaked T waves, widened QRS. Severe cases progress to cardiac arrest.
Management
During co-trimoxazole therapy, check potassium 3 days after start and daily if other risk factors are present. In older patients and chronic kidney disease, alternative antibiotics (nitrofurantoin, fosfomycin for UTI).