Drug Interaction Report

MONITOR: Coadministration with moderate inducers of CYP450 3A4 may decrease the plasma concentrations of istradefylline, which is primarily metabolized by CYP450 3A4 and 1A1. In study subjects, administration of istradefylline with the potent CYP450 3A4 inducer rifampin (600 mg daily for 20 days) led to a reduction in the peak plasma concentration (Cmax) and total systemic exposure (AUC(inf)) of istradefylline by 45% and 81%, respectively, when compared with istradefylline administered alone. No data are available regarding the effects that other, less potent CYP450 3A4 inducers will have on the pharmacokinetics of istradefylline.

MANAGEMENT: Caution is advised if istradefylline is used with moderate CYP450 3A4 inducers. Clinical monitoring of istradefylline should be considered whenever a moderate CYP450 3A4 inducer is added to or withdrawn from therapy. Patients should be monitored for diminished therapeutic effects.

ADJUST DOSE: Smoking tobacco may decrease the steady-state systemic exposure of istradefylline by 38% to 54%.

MANAGEMENT: The possibility of reduced therapeutic effects of istradefylline should be considered in smokers. The manufacturer recommends an istradefylline dosage of 40 mg once daily in patients who smoke 20 or more cigarettes (or the equivalent amount of another tobacco product) per day.