Critical
Amiodarone × Co-trimoxazole
Class III antiarrhythmics (Vaughan Williams)×Sulfonamide-trimethoprim combination
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.