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ORAP (PIMOZIDE): DRUG INTERACTIONS

Because Orap (Pimozide) tablets prolongs the QT interval of the electrocardiogram, an additive effect on QT interval would be anticipated if administered with other drugs, such as phenothiazines, tricyclic antidepressants or antiarrhythmic agents, which prolong the QT interval. Accordingly, pimozide should not be given with sotalol, dofetilide, quinidine, other Class Ia and III anti-arrhythmics, thioridazine, mesoridazine, chlorpromazine, sparfloxacin, droperidol, gatifloxacin, halofantrine, moxifloxacin, mefloquine, arsenic trioxide, pentamidine, levomethadyl acetate, probucol, dolasetron mesylate, tacrolimus, ziprasidone, or other drugs that have demonstrated QT prolongation as one of their pharmacodynamic effects. Also, the use of macrolide antibiotics in patients with prolonged QT intervals has been rarely associated with ventricular arrhythmias. Such concomitant administration should not be undertaken.

Pimozide and Celexa in a controlled study, a single dose of pimozide 2 mg coadministered with racemic citalopram 40 mg given once daily for 11 days was associated with a mean increase in QTc values of approximately 10 msec compared to pimozide given alone. Racemic citalopram did not alter the mean AUC or Cmax of pimozide. The mechanism of this pharmacodynamic interaction is not known.

Since Pimozide (Orap) is partly metabolized via CYP 3A4, it should not be administered concomitantly with inhibitors of this metabolic system, such as azole antifungal agents and protease inhibitor drugs.

As CYP 1A2 may also contribute to the metabolism of Pimozide (Orap) tablets, prescribers should be aware of the theoretical potential for drug interactions with inhibitors of this enzymatic system.

Orap may be capable of potentiating CNS depressants, including analgesics, sedatives, anxiolytics, and alcohol.

Rare case reports have suggested possible additive effects of Orap (Pimozide) and fluoxetine leading to bradycardia.

Concomitant administration of Orap (Pimozide) tablets and sertraline should be contraindicated.

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