Drug Interaction Report

Coadministration with inhibitors of P-glycoprotein (P-gp) may increase the plasma concentrations of prucalopride, which is thought to be a weak substrate of the efflux transporter. When given with the potent CYP450 3A4 and P-gp inhibitor, ketoconazole (200 mg twice daily), prucalopride peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 40%. This effect is unlikely to be clinically significant.

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.