Drug Interactions between felbamate and sorafenib

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of sorafenib. According to the prescribing information, sorafenib undergoes oxidative metabolism by hepatic CYP450 3A4 as well as glucuronidation by UGT1A9. When a single 400 mg oral dose of sorafenib was administered to healthy volunteers following treatment with the potent CYP450 3A4 inducer rifampin at a dosage of 600 mg once daily for 5 days, mean sorafenib systemic exposure (AUC) decreased by 37% compared to sorafenib administered alone. In another study conducted in 9 patients with advanced hepatocellular carcinoma initiating treatment with sorafenib 400 mg once daily or twice daily, addition of the potent CYP450 3A4 inducer enzalutamide at 160 mg daily starting on day 8 of sorafenib therapy reportedly led to a 60% reduction in mean AUC and 59% reduction in mean peak plasma concentration (Cmax) of sorafenib. The clinical significance of this interaction has not been established, but reduced therapeutic efficacy of sorafenib may occur. The interaction has not been studied with other, less potent inducers.

MANAGEMENT: The potential for diminished pharmacologic effects of sorafenib should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.