Drug Interaction Report

GENERALLY AVOID: Concurrent use of inhibitors of the proton pump (PPIs or potassium-competitive acid blockers [PCABs]) may decrease the oral bioavailability of atazanavir and substantially reduce its concentrations in plasma. Atazanavir solubility decreases with increasing pH, thus inhibition of gastric acid secretion may interfere with dissolution of the drug.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, use of PPIs or PCABs is not recommended in treatment-experienced patients receiving atazanavir with or without ritonavir or cobicistat. In treatment-naive patients receiving atazanavir with ritonavir or cobicistat, it is recommended that the dose of the PPI not exceed 20 mg/day of omeprazole, or equivalent, and doses should be separated by 12 hours. Some authorities recommend increasing the dose of atazanavir to 400 mg with 100 mg ritonavir when this combination is given with a PPI (UK). Atazanavir without ritonavir or cobicistat should not be coadministered with PPIs in treatment-naive patients.

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.