OBJECT DRUGS
PRECIPITANT DRUGS
Drugs That Inhibit CYP2D6 and Prolong the QT Interval:
- Amiodarone (Cordarone, etc.)
- Dronedarone (Multaq)
- Haloperidol (Haldol)
- Lumefantrine (Coartem)
- Quinidine (Quinidex)
- Ranolazine (Ranexa)
Comment:
Thioridazine can prolong the QT interval in a dose-dependent manner. Drugs that inhibit the cytochrome P450 isozymes involved in thioridazine metabolism (primarily CYP2D6) may increase the risk of ventricular arrhythmias such as torsades de pointes. Amiodarone and quinidine are strong inhibitors of CYP2D6, and also individually prolong the QT interval. Hence, the risk of serious arrhythmias is likely to be substantially increased. The product information for thioridazine states that it is contraindicated with known CYP2D6 inhibitors or drugs that increase the QT interval.
Class 1: Avoid Combination
- Avoid: Avoid the use of these drugs in patients receiving thioridazine.
- Use Alternative:
- Thioridazine: Most other phenothiazines produce less QT prolongation than thioridazine. Pimozide (Orap) can substantially prolong the QT interval and would not be a suitable substitute for thioridazine.
- Antiarrhythmics: It may be difficult to find an alternative antiarrhythmic that can be used safely with thioridazine. Several other antiarrhythmics such as disopyramide (Norpace), procainamide (Pronestyl), and sotalol (Betapace) can prolong the QT interval, and should be used only with extreme caution with thioridazine.
- Monitor: If combined therapy is necessary, monitor carefully for signs of delayed ventricular repolarization (prolonged QT interval) and symptoms of torsades de pointes including palpitations and syncope.