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.

GENERALLY AVOID: Grapefruit juice may significantly increase the systemic exposure to eliglustat. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because eliglustat is predicted to cause prolongation of the PR, QTc, and QRS cardiac intervals at substantially elevated plasma concentrations, consumption of grapefruit juice during treatment may increase the risk of bradycardia, atrioventricular block, cardiac arrest, and serious ventricular arrhythmias such as torsade de pointes.

MANAGEMENT: Patients treated with eliglustat should avoid consumption of grapefruit and grapefruit juice.