Dronedarone × Haloperidol

Both drugs prolong the QT interval on the electrocardiogram. Dronedarone prolongs the corrected QT interval (QTc) by about 10 ms and can itself cause arrhythmias when used with other drugs that favour arrhythmias (dronedarone SmPC). The haloperidol SmPC reports QT prolongation, ventricular arrhythmias and sudden death; the risk is higher with high doses, high plasma levels and parenteral use, especially intravenous. There is a second mechanism: dronedarone is a moderate CYP3A4 inhibitor and a weak CYP2D6 inhibitor (dronedarone SmPC), and haloperidol is partly cleared by both enzymes; with such inhibitors its levels may rise by 20–40%, in some cases by up to 100% (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, a ventricular tachycardia. The risk is higher with low potassium or magnesium (dronedarone and haloperidol SmPCs), bradycardia or heart disease (haloperidol SmPC). Haloperidol can also cause a fast heart rate and a drop in blood pressure on standing (haloperidol SmPC).

The combination is contraindicated: the Spanish haloperidol SmPC contraindicates haloperidol with drugs that prolong the QT interval and names dronedarone (haloperidol SmPC). The dronedarone SmPC approved by the European Medicines Agency (EMA) contraindicates it with drugs that can induce torsades de pointes and gives phenothiazines, tricyclic antidepressants, some macrolides and class I and III antiarrhythmics as examples; haloperidol is not on that list (dronedarone SmPC). Potassium and magnesium deficits are corrected before the start and checked during treatment (dronedarone and haloperidol SmPCs). Before haloperidol is started, an electrocardiogram (ECG) is recorded; if the corrected QT interval (QTc) lengthens, the haloperidol dose is reduced, and haloperidol is stopped if QTc exceeds 500 ms (haloperidol SmPC). On dronedarone the ECG is monitored, and dronedarone is stopped if QTc reaches 500 ms or more (dronedarone SmPC). Haloperidol solution for injection is given intramuscularly only; if it is given intravenously, the ECG is monitored continuously (haloperidol injection SmPC).