Clarithromycin × Haloperidol

Both drugs prolong the QT interval on the electrocardiogram. The clarithromycin SmPC reports QT prolongation and a risk of torsades de pointes with macrolides, clarithromycin included. The haloperidol SmPC reports QT prolongation, ventricular arrhythmias and sudden death; the risk is higher with high doses and high plasma levels. There is a second mechanism: clarithromycin is a strong CYP3A4 inhibitor (clarithromycin SmPC), and haloperidol is partly cleared by this enzyme, although its main pathways are different. With CYP3A4 inhibitors haloperidol levels may rise by 20–40%, in some cases by up to 100%, and the risk of QT prolongation rises with them (haloperidol SmPC).

QT prolongation on the electrocardiogram (ECG) causes no symptoms by itself. Palpitations, dizziness or fainting may occur. The dangerous complication is torsades de pointes, which can progress to ventricular fibrillation (clarithromycin SmPC). The risk is higher with low potassium or magnesium, coronary artery disease, severe heart failure, conduction disorders or marked bradycardia (clarithromycin and haloperidol SmPCs).

The combination is contraindicated: the Spanish haloperidol SmPC contraindicates haloperidol with drugs that prolong the QT interval and names clarithromycin (haloperidol SmPC). The clarithromycin label approved by the US Food and Drug Administration (FDA) says to avoid clarithromycin in patients who take QT-prolonging drugs (clarithromycin FDA label). Clarithromycin itself is contraindicated with low potassium or magnesium and with a history of QT prolongation (clarithromycin SmPC). The haloperidol SmPC also contraindicates azithromycin, erythromycin, levofloxacin and moxifloxacin. Before haloperidol is started, an electrocardiogram (ECG) is recorded and low potassium and magnesium are corrected; if the corrected QT interval (QTc) lengthens, the haloperidol dose is reduced, and haloperidol is stopped if QTc exceeds 500 ms (haloperidol SmPC).