Drug Interaction Report

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.

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.

ADJUST DOSING INTERVAL: Food may increase the extent of tecovirimat absorption following oral administration. When the recommended oral dose of tecovirimat (600 mg every 12 hours) was administered with a meal (approximately 600 calories and 25 g of fat) in healthy adults weighing less than 120 kg, tecovirimat absorption increased by 39% relative to fasting.

MANAGEMENT: Oral tecovirimat should be taken within 30 minutes after a full meal containing moderate or high fat (approximately 600 calories and 25 g of fat) with 6 to 8 ounces of water.