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: Pomegranates and grapefruit may increase the systemic exposure to ribociclib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in these fruits. Increased exposure to ribociclib may increase the risk of adverse effects such as infections, neutropenia, leukopenia, anemia, thrombocytopenia, anorexia, nausea, vomiting, diarrhea, stomatitis, alopecia, fatigue, headache, and abnormal liver function may be increased.

MANAGEMENT: Patients receiving ribociclib should avoid consumption of pomegranates or pomegranate juice and grapefruit or grapefruit juice during treatment.