Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of atazanavir, which is primarily metabolized by the isoenzyme.

MANAGEMENT: Caution is advised if atazanavir is used with CYP450 3A4 inhibitors, particularly potent ones like other protease inhibitors, macrolide antibiotics, itraconazole, ketoconazole, and nefazodone. Pharmacologic response to atazanavir should be monitored more closely whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy. In addition, many CYP450 3A4 inhibitors are also substrates of the isoenzyme, thus pharmacologic response to these agents should also be monitored during coadministration with atazanavir.

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.