Dronedarone × Erythromycin

Both drugs prolong the QT interval. The dronedarone label lists erythromycin among drugs that can induce torsade de pointes and contraindicates the combination because of the risk of proarrhythmia. Erythromycin also moderately inhibits the enzyme CYP3A4 and the transporter P-glycoprotein (erythromycin label). The liver breaks down dronedarone mainly through this enzyme. Erythromycin 500 mg three times a day for 10 days raised steady-state dronedarone levels 3.8-fold (dronedarone label, European Medicines Agency, EMA). The QT interval gets longer as dronedarone concentration rises (dronedarone label, US Food and Drug Administration, FDA). Dronedarone is a class III antiarrhythmic. The label of intravenous erythromycin contraindicates erythromycin with class Ia and III antiarrhythmics, which also prolong the QT interval.

The main risk is ventricular arrhythmia from a prolonged QT interval, up to torsade de pointes: palpitations, skipped beats, dizziness, fainting. Deaths from these arrhythmias have been reported during erythromycin treatment, and older people are more sensitive to its effect on the QT interval. A fast intravenous infusion of erythromycin can by itself prolong the QT interval and cause arrhythmia or low blood pressure. A slow pulse is common with dronedarone. As its concentration rises, the QT and PR intervals on the electrocardiogram (ECG) get longer.

The combination is contraindicated (dronedarone labels, European Medicines Agency, EMA, and US Food and Drug Administration, FDA). Both labels name erythromycin. The contraindication also applies to intravenous erythromycin. The FDA dronedarone label does not limit it to any route of administration. The label of intravenous erythromycin contraindicates its use with class III antiarrhythmics (Spanish Agency of Medicines and Medical Devices, AEMPS), and dronedarone belongs to this class (dronedarone label, EMA). If erythromycin has been started during dronedarone treatment, stop dronedarone: the label requires stopping it whenever any contraindicated condition develops (dronedarone label, EMA). After stopping 400 mg twice daily, dronedarone and its metabolite are fully cleared from plasma within 2 weeks (dronedarone label, EMA). The documents set no specific interval before starting erythromycin. Correct potassium and magnesium before starting dronedarone and keep them in the normal range during treatment (dronedarone labels, EMA and FDA). Do not give erythromycin to patients with low potassium or magnesium (erythromycin label, AEMPS). Monitor the electrocardiogram (ECG) during dronedarone treatment and stop dronedarone if the QTc interval (QT corrected for heart rate) reaches 500 milliseconds or more (dronedarone label, EMA). Infuse intravenous erythromycin over 60 minutes, and over a longer time in patients with risk factors or a history of arrhythmia (intravenous erythromycin label, AEMPS).