Drug Interaction Report

MONITOR: Coadministration with sorafenib may increase the plasma concentrations of capecitabine and its active metabolite, 5-fluorouracil (5-FU). The mechanism of interaction has not been described. According to the sorafenib labeling, concomitant use of capecitabine (750 to 1050 mg/m2 twice daily on days 1 to 14 every 21 days) with sorafenib (200 or 400 mg twice daily continuously) increased capecitabine exposure by 15% to 50% and 5-FU exposure by 0% to 52%. The clinical significance of these modest changes is unknown. Sorafenib pharmacokinetics were not significantly altered by capecitabine.

MANAGEMENT: Caution may be advisable when capecitabine is used with sorafenib. Patients should be monitored closely for potential toxicities of capecitabine such as diarrhea, hand and foot syndrome, hyperbilirubinemia, myelosuppression and cardiotoxicity, and the dosage adjusted accordingly.

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.