Drug Interaction Report

Theoretically, coadministration with CYP450 3A inhibitors may increase the plasma concentrations of pimecrolimus, which has been shown in vitro to undergo metabolism by this subfamily of hepatic microsomal enzymes. Although clinically significant drug interactions are not expected due to minimal systemic absorption of topically administered pimecrolimus, the possibility cannot be ruled out. The manufacturer recommends caution in patients with widespread and/or erythrodermic disease.

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.