Drug Interaction Report

GENERALLY AVOID: Coadministration of substrates of CYP450 3A4, 2D6, or 2C8 with pazopanib may increase their plasma concentrations. The mechanism is inhibition of CYP450-mediated metabolism by pazopanib. In clinical studies, the concomitant use of pazopanib increased the AUC and Cmax of midazolam by 30%, and increased the AUC and Cmax of paclitaxel by 26% and 31%, respectively.

MANAGEMENT: Due to the potential for adverse effects, the concomitant use of pazopanib with drugs that have narrow therapeutic ranges and that are substrates of CYP450 3A4, 2D6, or 2C8 is not recommended.

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.

ADJUST DOSING INTERVAL: Consumption of food can decrease the rate and extent of gastrointestinal absorption of sirolimus. Also, the consumption of grapefruit juice may result in increased sirolimus trough concentrations.

MANAGEMENT: Experts recommend that this drug be taken either at least one hour prior to eating or consistently with or without food to avoid variations in sirolimus blood levels. The manufacturer recommends against using grapefruit juice for dilution of sirolimus doses. Patients should be monitored for clinical and laboratory evidence of altered immunosuppressant effects.