Major
Amiodarone × Clarithromycin
Class III antiarrhythmics (Vaughan Williams)×Macrolide antibiotic
Mechanism
Dual mechanism: both prolong QT, and clarithromycin blocks CYP3A4 – a partial amiodarone clearance route. Amiodarone and its active metabolite (N-desethyl-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 antibiotics: azithromycin or doxycycline (minimal CYP3A4 interaction). If clarithromycin is needed, ECG before start and every 3 days during therapy, with potassium and magnesium maintained.