Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 2C8 may increase the plasma concentrations of tucatinib, which is primarily metabolized by the isoenzyme. When gemfibrozil (600 mg twice daily), a potent CYP450 2C8 inhibitor, was administered with a single tucatinib dose of 300 mg, tucatinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.6-fold and 3-fold, respectively.

MANAGEMENT: Increased monitoring is advised if tucatinib is coadministered with CYP450 2C8 inhibitors. Dosage adjustments may be required based on clinical response and tolerance.

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.