Drug Interaction Report

MONITOR: Coadministration with sorafenib may increase the plasma concentrations of irinotecan and its pharmacologically active metabolite, SN-38. The proposed mechanism is sorafenib inhibition of CYP450 3A4 and UGT1A1, the enzymes responsible for the metabolic clearance of irinotecan and SN-38, respectively. Concomitant treatment with sorafenib has been reported to increase irinotecan systemic exposure (AUC) by 26% to 42% and SN-38 systemic exposure by 67% to 120%. The clinical significance of these changes is unknown.

MANAGEMENT: Sorafenib product labeling recommends caution during coadministration with irinotecan. High plasma levels of irinotecan and SN-38 may result in increased toxicities such as severe diarrhea, neutropenia, sepsis, and thromboembolism.

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.