Major
Co-trimoxazole × Enalapril
Sulfonamide-trimethoprim combination×Angiotensin-converting enzyme inhibitors (ACEi)
Mechanism
Trimethoprim blocks collecting duct sodium channels (amiloride-like mechanism) and reduces potassium secretion. Enalapril (ACE-I) additionally retains potassium through aldosterone suppression.
Symptoms
Muscle weakness, paraesthesia in the limbs, slowed pulse, arrhythmias. ECG shows peaked T waves and widened QRS. Severe cases progress to cardiac arrest. Symptoms typically appear within 1–2 weeks of starting the combination.
Management
During co-trimoxazole therapy, check potassium 3–5 days after start. In older patients and chronic kidney disease, prefer alternative antibiotics: nitrofurantoin or fosfomycin.