Critical
Dronedarone × Ketoconazole
Class III antiarrhythmic×Systemic antimycotics. Imidazole derivatives
Mechanism
Ketoconazole is a strong CYP3A4 inhibitor, the main dronedarone clearance route. Dronedarone plasma levels rise 17-fold. FDA Multaq Section 4.3 specifically lists strong CYP3A4 inhibitors.
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 rises with hypokalaemia and hypomagnesaemia.
Management
The combination is not prescribed. Alternative antifungals: echinocandins (micafungin, caspofungin) or fluconazole for candidiasis (weaker CYP3A4 effect). Alternative antiarrhythmic: amiodarone or catheter ablation.