Drug Interaction Report

MONITOR: Coadministration with ribociclib may increase the plasma concentrations and pharmacologic effects of drugs that are substrates of breast cancer resistance protein (BCRP), organic cation transporter-2 (OCT-2), multidrug and toxin extrusion 1 (MATE1), and/or bile salt efflux pump (BSEP) transporters. The proposed mechanism, based on in vitro data, is decreased clearance due to ribociclib-mediated inhibition of these transport proteins at clinically relevant concentrations.

MANAGEMENT: Caution is advised if ribociclib is used concomitantly with drugs that are substrates of BCRP, OCT-2, MATE1, and/or BSEP transport proteins, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever ribociclib is added to or withdrawn from therapy with these drugs. Patients should be monitored for the development of adverse effects.

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.