Drug Interaction Report

ADJUST DOSE: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations and risk of adverse effects 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.

MANAGEMENT: The manufacturer suggests that the maximum dose of istradefylline when coadministered with potent CYP450 3A4 inhibitors be reduced to 20 mg once daily. Patients should be monitored for adverse effects including dyskinesia, impulse control issues, dizziness, constipation, nausea, hallucinations, and insomnia.

ADJUST DOSE: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations and risk of adverse effects 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.

MANAGEMENT: The manufacturer suggests that the maximum dose of istradefylline when coadministered with potent CYP450 3A4 inhibitors be reduced to 20 mg once daily. Patients should be monitored for adverse effects including dyskinesia, impulse control issues, dizziness, constipation, nausea, hallucinations, and insomnia.

ADJUST DOSING INTERVAL: Administration of atazanavir with food enhances oral bioavailability and reduces pharmacokinetic variability. According to the manufacturer, administration with a light meal increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single 400 mg dose of atazanavir by 57% and 70%, respectively, relative to the fasting state. Administration with a high-fat meal resulted in a mean increase of 35% in atazanavir AUC and no change in Cmax compared to fasting. The coefficient of variation of AUC and Cmax decreased by approximately one-half when given with either a light or high-fat meal compared to the fasting state.

MANAGEMENT: To ensure maximal oral absorption, atazanavir should be administered with or immediately after a meal.

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.