Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of ribociclib, which is a substrate of the isoenzyme. Physiologically-based pharmacokinetic simulations (PBPK) suggest that a moderate CYP450 3A4 inducer, efavirenz, may decrease ribociclib Cmax and AUC by 37% and 60%, respectively. However, data with less potent CYP450 3A4 inducers are limited.

MANAGEMENT: The potential for diminished therapeutic effects of ribociclib should be considered when prescribed with inducers of CYP450 3A4, particularly moderate inducers including efavirenz and nevirapine. Pharmacologic effects of ribociclib should be monitored more closely whenever an inducer is added to or withdrawn from therapy. Alternative treatment may be required if an interaction is suspected.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

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.