Major
Dronedarone × Fluconazole
Class III antiarrhythmic×Antifungals, triazole derivatives
Mechanism
Dual mechanism. Fluconazole blocks CYP3A4 (the main dronedarone clearance route) and prolongs QT itself. Dronedarone plasma levels rise; QT effects add up.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
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.