Drug Interaction Report

MONITOR: Sirolimus may be systemically absorbed following topical administration. Theoretically, coadministration with inhibitors of CYP450 3A4 may increase the systemic exposure of sirolimus, which is a substrate of the isoenzyme. Significant increases in systemic exposure have been reported when oral sirolimus was coadministered with potent and moderate CYP450 3A4 inhibitors such as azole antifungal agents, macrolide antibiotics, protease inhibitors, and some calcium channel blockers. No formal studies to evaluate drug interactions with topical sirolimus have been conducted.

MANAGEMENT: Caution is advised if topical sirolimus is prescribed with potent or moderate CYP450 3A4 inhibitors. Patients should be monitored for systemic sirolimus adverse effects including immunosuppression, infection, hyperlipidemia, malignancy, and interstitial lung disease.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of crizotinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Because crizotinib is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death.

Food has no significant effect on the gastrointestinal absorption of crizotinib. According to the product labeling, a high-fat meal reduced crizotinib peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 14%.

MANAGEMENT: Patients treated with crizotinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Crizotinib may be taken without regards to food.