Drug Interaction Report

MONITOR: Coadministration with moderate inhibitors of CYP450 3A4 may increase the plasma concentrations of istradefylline, which is primarily metabolized by CYP450 3A4 and 1A1. In study subjects, administration of a single 40 mg dose of istradefylline with the potent CYP450 3A4 inhibitor ketoconazole (200 mg twice daily for 4 days) increased the total systemic exposure (AUC(inf)) of istradefylline by 2.5-fold. No data are available regarding the effects that other, less potent CYP450 3A4 inhibitors will have on the pharmacokinetics of istradefylline.

MANAGEMENT: Caution is advised if istradefylline is used with moderate CYP450 3A4 inhibitors. It is unknown if istradefylline will require a dosage adjustment if coadministered with a moderate CYP450 3A4 inhibitor. Clinical and laboratory monitoring of istradefylline should be considered whenever a moderate CYP450 3A4 inhibitor is added to or withdrawn from therapy. Patients should be monitored for adverse effects including dyskinesia, impulse control issues, dizziness, constipation, nausea, hallucinations, and insomnia.

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.