clarithromycin and amiodarone

Clarithromycin inhibits CYP3A4, the cytochrome P450 enzyme that metabolises amiodarone, leading to increased amiodarone plasma concentrations. Additionally, both drugs independently prolong the QT interval, producing an additive pharmacodynamic effect.

Co-administration increases the risk of QT interval prolongation and life-threatening ventricular arrhythmias such as torsades de pointes. The combined effect of elevated amiodarone levels and additive QT prolongation can lead to sudden cardiac death.

Coadministration is contraindicated. Avoid the combination and consider alternative antibacterial therapy. If coadministration is absolutely necessary, it should be done in a hospital setting with continuous ECG monitoring and immediate availability of resuscitation facilities, but ideally the combination should not be used.

This interaction is well established and documented in product labels and clinical guidelines. Case reports describe torsades de pointes and cardiac arrest with the combination.