Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly 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. In addition, some of the known potent inducers of CYP450 3A4 such as apalutamide, encorafenib, and enzalutamide can cause QT interval prolongation and may have additive effects with sorafenib, resulting in increased risk of ventricular arrhythmias including torsade de pointes and sudden death.

MANAGEMENT: Concomitant use of sorafenib with potent CYP450 3A4 inducers should be avoided when possible.

ADJUST DOSING INTERVAL: Food may reduce the oral absorption and bioavailability of sorafenib. According to the product labeling, sorafenib bioavailability was reduced by 29% when administered with a high-fat meal compared to administration in the fasted state. When given with a moderate-fat meal, bioavailability was similar to that in the fasted state.

MANAGEMENT: To ensure maximal and consistent oral absorption, sorafenib should be taken at least one hour before or two hours after eating.