Drug Interaction Report

Coadministration with rizatriptan may alter the plasma concentrations of drugs that are primarily metabolized by CYP450 2D6. Rizatriptan has been shown to be a competitive inhibitor of CYP450 2D6 in vitro, but only at high, clinically irrelevant concentrations and a clinically significant inhibitory effect on CYP450 2D6 has not been demonstrated in clinical drug interaction studies. Based on these observations, rizatriptan may be administered with CYP450 2D6 substrates without the need for increased clinical monitoring

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.