In a combined analysis from several clinical studies, atazanavir/ritonavir 300/100 mg co-administered with tenofovir disoproxil fumarate 300 mg (n=39) was compared to atazanavir/ritonavir 300/100 mg (n=33). Atazanavir AUC, Cmax and Cmin decreased 22%, 16% and 23%, respectively. Coadministration of tenofovir disoproxil fumarate (300 mg once daily) with atazanavir/ritonavir (300 mg/100 mg once daily) was studied in healthy volunteers. Tenofovir-DF AUC, Cmax and Cmin increased 37%, 34% and 29%, respectively. The mechanism of interaction between atazanavir and tenofovir disoproxil fumarate is unknown. The efficacy of Reyataz/ritonavir in combination with tenofovir disoproxil fumarate in treatment-experienced patients has been demonstrated in clinical study 045 and in treatment naive patients in clinical study 138. When coadministered with tenofovir disoproxil fumarate, it is recommended that Reyataz 300 mg be given with ritonavir 100 mg and tenofovir disoproxil fumarate 300 mg (all as a single dose with food). Patients should be closely monitored for tenofovir disoproxil fumarate-associated adverse reactions, including renal disorders. Reyataz given without ritonavir should not be considered in patients treated with a backbone regimen containing tenofovir disoproxil.

Tenofovir DF may decrease the AUC and Cmin of atazanavir. When coadministered with tenofovir DF in adults, it is recommended that Reyataz 300 mg be given with ritonavir 100 mg and tenofovir DF 300 mg (all as a single daily dose with food). Reyataz increases tenofovir concentrations. The mechanism of this interaction is unknown. Higher tenofovir concentrations could potentiate tenofovir-associated adverse reactions, including renal disorders. Patients receiving Reyataz and tenofovir DF should be monitored for tenofovir-associated adverse reactions. Coadministration of tenofovir-DF (300 mg, once daily) with atazanavir (400 mg, once daily) was studied in 34 healthy volunteers. Atazanavir Cmax, AUC and Cmin decreased 21%, 25% and 40%, respectively. Tenofovir Cmax, AUC and Cmin increased 14%, 24%, and 22%, respectively (n=33). Coadministration of tenofovir-DF (300 mg, once daily) with atazanavir/ritonavir (300 mg/100 mg, once daily) was studied in 12 healthy volunteers. Atazanavir Cmax, AUC and Cmin decreased 28%, 25% and 23%, respectively (n=10). Tenofovir Cmax, AUC and Cmin increased 34%, 37% and 29%, respectively. Note that similar results were observed in studies where administration of tenofovir DF and Reyataz was separated by 12 hours. Atazanavir 300 mg plus ritonavir 100 mg results in higher atazanavir exposure than atazanavir 400 mg. The geometric mean values of atazanavir pharmacokinetic parameters when coadministered with ritonavir and tenofovir DF were: Cmax = 3190 ng/mL, AUC = 34459 ng.h/mL, and Cmin = 491 ng/mL. Study was conducted in HIV-infected individuals.

Coadministration of atazanavir (400 mg once daily for 14 days) and tenofovir-DF (300 mg once daily) to 33 subjects increased tenofovir Cmax (14%), AUC (24%) and Cmin (22%). Atazanavir Cmax, AUC and Cmin decreased by 21%, 25% and 40% respectively. Coadministration of tenofovir-DF and atazanavir/ritonavir (300/100 mg once daily for 42 days) increased tenofovir Cmax, AUC and Cmin by 34%, 37% and 29%, respectively; atazanavir Cmax, AUC and Cmin decreased by 28%, 25%, and 23%, respectively. In HIV-infected patients, the addition of tenofovir-DF to atazanavir 300 mg plus ritonavir 100 mg, resulted in AUC and Cmin values of atazanavir that were 2.3- and 4-fold higher than the respective values observed for atazanavir 400 mg when given alone. When coadministered with tenofovir-DF, it is recommended that atazanavir 300 mg is given with ritonavir 100 mg. Tenofovir-DF should not be coadministered with atazanavir without ritonavir. Patients receiving tenofovir-DF concomitantly with ritonavir-boosted atazanavir should be monitored for tenofovir-associated adverse reactions. Tenofovir-DF should be discontinued in patients who develop tenofovir-associated adverse reactions. 

Atazanavir trough concentrations were determined in 43 HIV+ subjects receiving unboosted atazanavir (400 mg once daily) in the presence of tenofovir-DF. The median trough concentration was 242 (range 106-1100) ng/ml with 8 subjects having low trough concentrations (<150 ng/ml). Following a dose increase to 600 mg once daily in 4/8 subjects, atazanavir trough concentrations were 222-294 ng/ml. Viral load results were available for 36 subjects, 31 of whom were undetectable (<50 copies/ml) at baseline. 30 remained <50 copies/ml and all were <100 copies/ml at last follow up. Five subjects had viral loads >50 copies/ml at baseline, of whom 3 were undetectable at last follow up. 

The pharmacokinetic effects of the coadministration of tenofovir-DF (300 mg once daily) and unboosted atazanavir were studied in HIV-negative subjects. A dosing strategy that would provide atazanavir and tenofovir exposures comparable to each drug when dosed alone was evaluated. The strategies employed were dosing the ATV (400 mg once daily) and TDF 12 hours apart and increasing the ATV dose to 600 mg once daily. The temporal 12-hour separation of ATV 400 mg resulted in a decrease in ATV Cmax, AUC, Cmin of 10%, 17%, and 28%, respectively and an increase in TDF Cmax, AUC and Cmin of 43%, 37%, and 38%, respectively. The simultaneous administration of 600 mg ATV with TDF resulted in a decrease in ATV Cmax, AUC and Cmin of 27%, 36%, and 41%, respectively and an increase in TDF Cmax, AUC and Cmin of 41%, 59%, and 74%, respectively. Based on these findings the authors continue to recommend that when co-dosed with TDF, ATV (300 mg once daily) should be combined with RTV (100 mg once daily). 

The pharmacokinetics of atazanavir (400 mg once daily) with tenofovir-DF (300 mg once daily) and/or ddI-EC were investigated in 36 healthy subjects. Addition of tenofovir-DF decreased atazanavir Cmax, AUC and Cmin (21%, 25% and 40% respectively); tenofovir Cmax, AUC and Cmin were increased by 1.14-, 1.24- and 1.22-fold respectively in the presence of atazanavir. In the presence of tenofovir-DF and ddI-EC (250 mg once daily with food), atazanavir Cmax, AUC and Cmin decreased by 24%, 26% and 39% respectively (compared to atazanavir alone); tenofovir Cmax, AUC and Cmin increased 1.12-, 1.25- and 1.25-fold respectively (compared to tenofovir alone).