Drug Interaction Report

GENERALLY AVOID: Coadministration with rolapitant may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein (P-gp) efflux transporter. When a 0.5 mg dose of digoxin, a P-gp probe substrate, was administered with a 180 mg dose of rolapitant, digoxin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 70% and 30%, respectively.

MANAGEMENT: Concomitant use of rolapitant with drugs that are P-gp substrates should generally be avoided. If concomitant administration is unavoidable, caution is advised, particularly with drugs that have a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever rolapitant is added to or withdrawn from therapy.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of pazopanib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Although not studied, the interaction may increase the risk of QT interval prolongation and torsade de pointes arrhythmia as well as severe and fatal hepatotoxicity associated with the use of pazopanib.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of pazopanib. The mechanism of interaction is unknown. Administration of pazopanib with a high-fat or low-fat meal results in an approximately 2-fold increase in peak plasma concentration (Cmax) and systemic exposure (AUC).

MANAGEMENT: Patients treated with pazopanib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Pazopanib should be administered at least one hour before or two hours after a meal.