Major
Amiodarone × Ketoconazole
Class III antiarrhythmics (Vaughan Williams)×Systemic antimycotics. Imidazole derivatives
Mechanism
Ketoconazole strongly blocks CYP3A4 – the N-deethylation pathway of amiodarone. Amiodarone and its active metabolite (N-desethyl-amiodarone) levels rise; QT effect intensifies.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid the combination. Alternative antifungals: terbinafine (no CYP3A4 effect) for dermatophytosis or echinocandins for systemic mycoses.
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.