Major
Amiodarone × Fluconazole
Class III antiarrhythmics (Vaughan Williams)×Antifungals, triazole derivatives
Mechanism
Dual mechanism: fluconazole prolongs QT (additive with amiodarone) and blocks CYP3A4 – a partial amiodarone clearance route. Amiodarone plasma levels rise.
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: echinocandins (micafungin, caspofungin) for systemic mycoses or terbinafine for dermatophytosis. If fluconazole is needed, ECG before start and every 3 days during therapy.