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as well as clinical and laboratory monitoring may be appropriate for some drugs whenever istradefylline is added to or withdrawn from therapy.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

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.