Drug Interaction Report

MONITOR: Coadministration with istradefylline may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein (P-gp) transporter. The proposed mechanism is inhibition of P-glycoprotein-mediated drug efflux by istradefylline. When a single dose of the P-gp probe substrate digoxin (0.4 mg) was administered with istradefylline (40 mg daily for 21 days), the Cmax and total systemic exposure (AUC(inf)) of digoxin was increased by 33% and 21%, respectively, when compared with digoxin alone.

MANAGEMENT: Caution is advised when istradefylline is used concurrently with drugs that are known P-gp substrates, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever istradefylline is added to or withdrawn from therapy.

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.

Food enhances the oral absorption and bioavailability of tenofovir, the active entity of tenofovir disoproxil fumarate. According to the product labeling, administration of the drug following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of tenofovir by approximately 14% and 40%, respectively, compared to administration in the fasting state. However, administration with a light meal did not significantly affect the pharmacokinetics of tenofovir compared to administration in the fasting state. Food delays the time to reach tenofovir Cmax by approximately 1 hour. Tenofovir disoproxil fumarate may be administered without regard to meals.