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: Administration of atazanavir with food enhances oral bioavailability and reduces pharmacokinetic variability. According to the manufacturer, administration with a light meal increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single 400 mg dose of atazanavir by 57% and 70%, respectively, relative to the fasting state. Administration with a high-fat meal resulted in a mean increase of 35% in atazanavir AUC and no change in Cmax compared to fasting. The coefficient of variation of AUC and Cmax decreased by approximately one-half when given with either a light or high-fat meal compared to the fasting state.

MANAGEMENT: To ensure maximal oral absorption, atazanavir should be administered with or immediately after a meal.