Drug Interaction Report

Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of atogepant, which is primarily metabolized by the isoenzyme. When atogepant was administered with the potent CYP450 3A4 inhibitor itraconazole in healthy study subjects, atogepant peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 2.2- and 5.5-fold, respectively. However, moderate and weak inhibitors may interact to a much lesser extent. Population pharmacokinetic modeling has suggested that moderate (e.g., cyclosporine, ciprofloxacin, fluconazole, fluvoxamine, grapefruit juice) or weak (e.g., cimetidine, esomeprazole) CYP450 3A4 inhibitors may increase atogepant AUC by 1.7- and 1.1-fold, respectively. The changes in atogepant exposure when coadministered with moderate or weak CYP450 3A4 inhibitors are not expected to be clinically significant.

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.