Drug Interactions between bexarotene and Kisqali Femara Co-Pack

MONITOR: Coadministration with bexarotene may decrease the plasma concentrations of drugs that are primarily metabolized by CYP450 3A4. The proposed mechanism is increased clearance due to induction of CYP450 3A4 activity by bexarotene, particularly at dosages above 300 mg/m2/day. In a study of patients with non-small cell lung cancer receiving bexarotene (400 mg/m2 orally once a day) plus either paclitaxel/carboplatin or cisplatin/vinorelbine chemotherapy, treatment with atorvastatin (a CYP450 3A4 substrate) or fenofibrate was given to manage bexarotene-induced hyperlipidemia. Investigators reported that bexarotene decreased mean atorvastatin systemic exposure (dose-corrected AUC) by approximately 50%, whereas atorvastatin had no significant effect on bexarotene plasma concentrations. The AUC of paclitaxel (200 mg/m2 IV over 3 hours), a substrate of both CYP450 3A4 and 2C8, was also decreased by 19% when coadministered with bexarotene. According to the product labeling, bexarotene may decrease the plasma concentrations of another CYP450 3A4 substrate, tamoxifen, by 35%.

MANAGEMENT: Caution is advised if bexarotene is prescribed concomitantly with medications that are primarily metabolized by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever bexarotene is added to or withdrawn from therapy.

MONITOR: Coadministration with ribociclib may increase the plasma concentrations and pharmacologic effects of drugs that are substrates of CYP450 3A4. The proposed mechanism is decreased clearance due to ribociclib-mediated inhibition of CYP450 3A4 metabolism. In healthy study subjects, administration of midazolam, a sensitive CYP450 3A4 substrate, with multiple 400 mg daily doses of ribociclib increased the midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) by 2.1-fold and 3.8-fold, respectively, compared to midazolam administered alone. When given at a clinically relevant dose of 600 mg daily, ribociclib is predicted to increase midazolam Cmax and AUC by 2.4-fold and 5.2-fold, respectively.

MANAGEMENT: Caution is advised when ribociclib is used concomitantly with drugs that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever ribociclib is added to or withdrawn from therapy.

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.