Amiodarone × Clarithromycin

Both drugs prolong the QT interval, and their effects on the heart add up, raising the risk of torsades de pointes (amiodarone SmPC). Clarithromycin inhibits CYP3A4, which clears amiodarone, so amiodarone levels may rise (amiodarone SmPC). The US Food and Drug Administration (FDA) also describes the reverse effect: amiodarone slows the clearance of macrolides other than azithromycin (amiodarone FDA label). Amiodarone is eliminated very slowly, and its interactions can persist for months after it is stopped (amiodarone SmPC).

QT prolongation on the electrocardiogram, palpitations, dizziness, fainting. In severe cases, torsades de pointes with a risk of ventricular fibrillation and sudden cardiac death. The risk is higher with low potassium or magnesium, marked bradycardia, coronary artery disease and in older patients.

Avoid the combination. The US Food and Drug Administration (FDA) advises against clarithromycin in patients taking class III antiarrhythmics, including amiodarone (clarithromycin FDA label). The amiodarone FDA label advises avoiding certain macrolides with amiodarone, both as QT-prolonging drugs and as inhibitors of its metabolism (amiodarone FDA label). CYP3A4 inhibitors should be avoided during amiodarone treatment (amiodarone SmPC). QT-prolonging drugs, clarithromycin included, are combined with amiodarone only after a careful assessment of benefit and risk for the individual patient and with QT monitoring (amiodarone SmPC). Clarithromycin is contraindicated in patients with a history of QT prolongation or ventricular arrhythmia and in those with low potassium or magnesium (clarithromycin SmPC). The interaction remains possible for several months after amiodarone is stopped (amiodarone SmPC).