Critical
Clarithromycin × Dronedarone
Macrolide antibiotic×Class III antiarrhythmic
Mechanism
Clarithromycin is a strong CYP3A4 inhibitor and prolongs QT itself. Dronedarone is cleared via CYP3A4 and also prolongs QT. Double mechanism: dronedarone levels rise 4-fold plus additive QT prolongation. 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 antibiotics: azithromycin (minimal CYP3A4 effect and weaker QT effect) or doxycycline by susceptibility.