Drug Interaction Report

MONITOR: Theoretically, coadministration with CYP450 3A4 inhibitors may increase the plasma concentrations of topical tacrolimus. The proposed mechanism involves inhibition of CYP450 3A4-mediated metabolism of tacrolimus, which is primary metabolized by this isoenzyme. However, systemic exposure from topical tacrolimus is reported to be minimal (less than 1 ng/mL) and so clinically significant drug interactions are not expected. Nevertheless, the possibility of an interaction cannot be ruled out.

MANAGEMENT: According to the manufacturer, caution is advised if topical tacrolimus is prescribed with CYP450 3A4 inhibitors. Patients should be monitored for systemic tacrolimus adverse effects including immunosuppression, infection, hyperkalemia, malignancy, nephrotoxicity, neurotoxicity, and hypertension.

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.