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: Coadministration with grapefruit juice is likely to increase the plasma concentrations of ponatinib, which is primarily metabolized by CYP450 3A4. However, the interaction has not been studied. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: The consumption of grapefruit, grapefruit juice, and supplements that contain grapefruit extract should be avoided during treatment with ponatinib.