Drug Interaction Report

GENERALLY AVOID: Concurrent use of proton pump inhibitors 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 proton pump inhibitors 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 proton-pump inhibitor 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 proton pump inhibitor (UK). Atazanavir without ritonavir or cobicistat should not be coadministered with proton pump inhibitors in treatment-naive patients.

ADJUST DOSING INTERVAL: Food may interfere with the absorption of esomeprazole. The manufacturer reports that the area under the concentration-time curve for esomeprazole following a single 40 mg dose was 33% to 53% lower when administered after food intake as opposed to during fasting conditions.

MANAGEMENT: Esomeprazole should be taken at least one hour before meals. When administered to patients receiving continuous enteral nutrition, some experts recommend that the tube feeding should be interrupted for at least 1 hour before and 1 hour after the dose of esomeprazole is given.

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.