Drug Interaction Report

MONITOR CLOSELY: Pimozide can cause dose-related prolongation of the QT interval. While clinical data are lacking, the coadministration of pimozide and agents that can produce hypokalemia and/or hypomagnesemia (e.g., potassium-wasting diuretics, amphotericin B, cation exchange resins) may result in elevated risk of ventricular arrhythmias, including ventricular tachycardia and torsade de pointes, because of additive arrhythmogenic potential.

MANAGEMENT: Caution is advised when pimozide must be used concomitantly with medications that can cause potassium and/or magnesium disturbances. Serum electrolytes should be monitored and any abnormalities corrected prior to initiating therapy with pimozide.

GENERALLY AVOID: Theoretically, the coadministration with grapefruit juice may increase the plasma concentrations of pimozide. The mechanism is decreased clearance of pimozide due to inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The use of pimozide alone has been associated with dose-dependent prolongation of the QT interval. Although clinical data are lacking, this interaction may result in potentiation of the proarrhythmic effect of pimozide and consequently an increased risk of ventricular arrhythmias such as ventricular tachycardia and torsade de pointes. In addition, alcohol may potentiate some of the pharmacologic effects of pimozide. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: The manufacturer recommends avoiding grapefruit juice (and probably grapefruits) during therapy with pimozide. Patients should also be advised to avoid or limit consumption of alcohol.