Clarithromycin × Domperidone

The liver breaks down domperidone mainly through the enzyme CYP3A4, and clarithromycin strongly inhibits this enzyme (domperidone and clarithromycin prescribing information). In vitro data suggest that drugs which markedly inhibit CYP3A4 raise domperidone plasma levels. The documents give no study or numbers with clarithromycin. Both drugs prolong the QT interval on the electrocardiogram on their own, so the arrhythmia risk rises in two ways: through higher domperidone levels and through added effects on the heart (domperidone prescribing information).

The main risk is heart rhythm disorders: QT interval prolongation on the electrocardiogram, ventricular tachycardia, ventricular fibrillation and torsade de pointes (clarithromycin prescribing information). Epidemiological studies have linked domperidone to serious ventricular arrhythmias and sudden cardiac death. The risk was higher in people over 60, at daily doses above 30 mg and with concomitant QT-prolonging drugs or inhibitors of the enzyme CYP3A4 (domperidone prescribing information). An arrhythmia attack shows as sudden strong palpitations, dizziness or fainting.

The combination is contraindicated (clarithromycin and domperidone prescribing information, Spanish Agency of Medicines and Medical Devices, AEMPS). The clarithromycin document names domperidone among contraindicated drugs. The domperidone document contraindicates strong inhibitors of the enzyme CYP3A4 and gives clarithromycin as an example (AEMPS). Among macrolide antibiotics, the domperidone document allows only azithromycin and roxithromycin with caution and places clarithromycin among the contraindicated drugs. Each drug on its own is contraindicated in people with a prolonged QT interval or low potassium or magnesium, and domperidone also with bradycardia or congestive heart failure (clarithromycin and domperidone prescribing information). Use domperidone at the lowest effective dose, no more than 30 mg a day in adults and usually for no longer than one week (domperidone prescribing information). Stop domperidone if signs of arrhythmia appear during treatment, and tell patients in advance to report any cardiac symptoms as soon as possible (domperidone prescribing information).