Dronedarone × Quetiapine

Both drugs prolong the QT interval. Dronedarone prolongs the corrected QT interval (QTc) by about 10 ms (dronedarone SmPC). After quetiapine reached the market, QT prolongation was reported at therapeutic doses and in overdose (quetiapine SmPC). Together they raise the risk of torsades de pointes. Dronedarone is also a moderate CYP3A4 inhibitor (dronedarone SmPC), and quetiapine is cleared mainly by this enzyme (quetiapine SmPC), so quetiapine levels may rise.

QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.

The combination is avoided: the quetiapine label approved by the US Food and Drug Administration (FDA) advises against using it with class III antiarrhythmics, and dronedarone is one of them. The dronedarone SmPC contraindicates it with drugs that can induce torsades de pointes and lists them: phenothiazines, tricyclic antidepressants, some oral macrolides, class I and III antiarrhythmics; quetiapine is not on that list (dronedarone SmPC). If the combination is still needed, potassium and magnesium deficits are corrected before and during dronedarone treatment, the electrocardiogram (ECG) is checked regularly, and dronedarone is stopped if the corrected QT interval (QTc) reaches 500 ms or more (dronedarone SmPC). Quetiapine needs particular caution in older patients and in congenital long QT syndrome, heart failure, cardiac hypertrophy, low potassium or low magnesium (quetiapine SmPC).