Drug Interaction Report

GENERALLY AVOID: Coadministration with inhibitors of UGT1A1 may increase the plasma concentrations of belinostat, which is primarily (80% to 90%) metabolized by UGT1A1-mediated glucuronidation. Atazanavir, a UGT1A1 inhibitor, decreased the peak plasma concentration (Cmax) of belinostat by 33% but increased systemic exposure (AUC) by 1.4-fold.

MANAGEMENT: Concomitant use of belinostat with UGT1A1 inhibitors should generally be avoided. If concomitant use of a UGT1A1 inhibitor is unavoidable, the manufacturer recommends that the dosage of belinostat be decreased by 25%; 1,000 mg/m2 dose modified to 750 mg/m2, 750 mg/m2 dose modified to 562.5 mg/m2, and 500 mg/m2 dose discontinued for the duration of UGT1A1 inhibitor use and restarted at the previous dose after five half-lives of the UGT1A1 inhibitor. Patients should be monitored closely for potentially increased adverse effects of belinostat such as nausea, vomiting, diarrhea, thrombocytopenia, leukopenia (neutropenia and lymphopenia), anemia, infection, and hepatotoxicity.

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.