Drug Interactions between istradefylline and letermovir

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laboratory monitoring of istradefylline should be considered whenever a moderate CYP450 3A4 inhibitor is added to or withdrawn from therapy.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.