Drug Interaction Report

GENERALLY AVOID: Coadministration with atazanavir may increase the plasma concentrations of ethinyl estradiol and norethindrone and possibly other contraceptive hormones. The mechanism is atazanavir inhibition of CYP450 3A4 and UGT1A1, the enzymes responsible for the metabolic clearance of contraceptive hormones. In 19 study subjects, atazanavir (400 mg once a day for 14 days) increased the mean steady-state peak plasma concentration (Cmax), area under the concentration-time curve (AUC) and trough plasma concentration (Cmin) of ethinyl estradiol (Ortho-Novum 7/7/7) by 15%, 48% and 91%, respectively, compared to administration of the oral contraceptive alone. The Cmax, AUC and Cmin of norethindrone were increased by 67%, 110% and 262%, respectively. Decreased HDL or increased insulin resistance may be associated with elevated plasma concentrations of norethindrone.

MANAGEMENT: The manufacturer recommends alternate methods of nonhormonal contraception during atazanavir or atazanavir-ritonavir therapy.

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.