Tenofovir DF may decrease the AUC and Cmin of atazanavir. When co-administered with tenofovir DF, it is recommended that Evotaz and tenofovir DF 300 mg be given together with food. Atazanavir increases tenofovir concentrations. Higher concentrations could potentiate tenofovir-associated adverse reactions, including renal disorders. Patients receiving tenofovir disoproxil should be monitored for tenofovir-associated adverse reactions. Coadministration of tenofovir disoproxil fumarate (300 mg, once daily) with atazanavir (400 mg, once daily) decreased atazanavir AUC, Cmax and Cmin by 25%, 21% and 40%, respectively; tenofovir AUC, Cmax and Cmin increased by 24%, 14% and 22%, respectively. Coadministration of tenofovir-DF with cobicistat is expected to increase tenofovir plasma concentrations (AUC and Cmin increased by 23% and 55%). The mechanism of interaction between atazanavir and tenofovir-DF is unknown. Cobicistat has been shown to decrease estimated creatinine clearance due to inhibition of tubular secretion of creatinine without affecting actual renal glomerular function. Evotaz should not be initiated in patients with creatinine clearance less than 70 ml/min if any coadministered agent (e.g. tenofovir disoproxil) requires dose adjustment based on creatinine clearance.

Coadministration may decrease atazanavir exposure and increase tenofovir concentrations. Patients receiving Evotaz and tenofovir should be monitored for tenofovir-associated adverse reactions. Renal impairment, including cases of acute renal failure and Fanconi syndrome, has been reported when cobicistat was used in an antiretroviral regimen that contained tenofovir-DF. Therefore, coadministration of Evotaz and tenofovir-DF is not recommended in patients who have an estimated creatinine clearance below 70 mL/min. When Evotaz is used with tenofovir-DF, document urine glucose and urine protein at baseline and perform routine monitoring of estimated creatinine clearance, urine glucose, and urine protein during treatment. Measure serum phosphorus in patients at risk for renal impairment. Coadministration of Evotaz and tenofovir-DF in combination with concomitant or recent use of a nephrotoxic agent is not recommended.