CriticalClass III antiarrhythmics (Vaughan Williams)×Sulfonamide-trimethoprim combination
Updated · Methodology
Mechanism
Amiodarone prolongs the QT interval. Co-trimoxazole (trimethoprim + sulfamethoxazole) also prolongs QT and amplifies the effect in combination. UK MHRA Cordarone X SmPC Section 4.3 specifically lists QT-prolonging drugs as contraindications. Co-trimoxazole additionally inhibits CYP2C9, a partial amiodarone clearance route.
Symptoms
QT prolongation on ECG, dizziness, syncope, palpitations. Severe cases progress to torsades de pointes with risk of ventricular fibrillation. Risk rises with hypokalaemia (which co-trimoxazole can worsen).
Management
The combination is not prescribed. For UTI in patients on amiodarone, use a cephalosporin, nitrofurantoin, or fosfomycin. For Pneumocystis infection (where co-trimoxazole is irreplaceable), continuous ECG monitoring and daily potassium and magnesium checks.
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.
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Sources
- MHRA: Cordarone X 200 mg Tablets – Summary of Product Characteristics (2024)
- AEMPS: Ficha técnica: Amiodarona (nº registro 81291), sección 4.5 (2022)– AEMPS, CIMA, nº registro 81291, revisión 06/2022, sección 4.5