Drug Interaction Report

MONITOR: Coadministration with oral neomycin may decrease the bioavailability of sorafenib. The glucuronide conjugates of sorafenib are cleaved in the gastrointestinal tract by bacterial glucuronidase, which allows the unconjugated parent drug to be reabsorbed. Neomycin interferes with this enterohepatic recycling by suppressing bacteria with glucuronidase activity. In healthy volunteers, administration of sorafenib following pretreatment with oral neomycin 1 gram three times daily for 5 days resulted in a 54% reduction in sorafenib average systemic exposure (AUC). The effects of other antibiotics on sorafenib pharmacokinetics have not been studied.

MANAGEMENT: The possibility of a diminished therapeutic response to sorafenib should be considered during coadministration with oral neomycin.

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.