Drug Interactions between atazanavir / cobicistat and tenofovir alafenamide

ADJUST DOSE: Coadministration with tenofovir may decrease the plasma concentrations of unboosted atazanavir. The mechanism of the interaction has not been described. Reduced atazanavir plasma levels may lead to diminished virologic response and possible resistance to atazanavir. In healthy subjects, tenofovir (300 mg once daily) decreased the systemic exposure (AUC) and trough plasma concentration (Cmin) of unboosted atazanavir (400 mg once daily) by 25% and 40%, respectively, compared to administration of atazanavir alone. When ritonavir was added as a booster and given simultaneously with atazanavir 300 mg once daily and tenofovir to HIV-infected subjects, the AUC and Cmin of atazanavir were approximately 2.3- and 4-fold higher, respectively, than the values observed for unboosted atazanavir in healthy subjects.

MONITOR: The use of atazanavir boosted with either cobicistat or ritonavir may increase tenofovir plasma concentrations. Increased tenofovir plasma concentrations may increase the risk for tenofovir-related renal adverse effects, including renal impairment, renal failure, elevated creatinine, and Fanconi syndrome. The mechanism of this interaction has not been described. Cobicistat may decrease estimated creatinine clearance via inhibition of tubular secretion of creatinine; however, renal glomerular function does not appear to be affected. When given concomitantly with atazanavir 300 mg and ritonavir 100 mg once daily, the AUC and Cmin of tenofovir increased by 37% and 29%, respectively. When given concomitantly with cobicistat, the AUC and Cmin of tenofovir was also increased by 23% and 55%, respectively. Data are lacking to determine whether concomitant use of tenofovir with cobicistat-containing regimens is associated with a greater risk of renal complications compared with regimens that do not include cobicistat.

MANAGEMENT: Administration of unboosted atazanavir with tenofovir is not recommended. In patients requiring combination therapy with atazanavir and tenofovir, it is recommended that tenofovir 300 mg be administered with either atazanavir 300 mg-ritonavir 100 mg or atazanavir 300 mg-cobicistat 150 mg, all as a single daily dose with food. Initiation of cobicistat or cobicistat-containing regimens is not recommended in patients with CrCl less than 70 mL/min if any coadministered medicine requires dose adjustment based on renal function (including tenofovir) or is nephrotoxic. If concomitant therapy is necessary, monitoring of renal function is recommended, particularly in patients with risk factors for renal impairment.

MONITOR: Concomitant use of tenofovir with cobicistat may increase the risk for tenofovir-related renal adverse effects, including renal impairment, renal failure, elevated creatinine, and Fanconi syndrome. The mechanism of this interaction has not been described. Cobicistat may decrease estimated creatinine clearance via inhibition of tubular secretion of creatinine; however, renal glomerular function does not appear to be affected. When given concomitantly with cobicistat, the systemic exposure (AUC) and trough plasma concentrations (Cmin) of tenofovir was also increased by 23% and 55%, respectively. However, data are lacking to determine whether concomitant use of tenofovir with cobicistat-containing regimens is associated with a greater risk of renal complications compared with regimens that do not include cobicistat.

MANAGEMENT: Initiation of cobicistat or cobicistat-containing regimens is not recommended in patients with CrCl less than 70 mL/min if any coadministered medicine requires dose adjustment based on renal function (including tenofovir), or is nephrotoxic. If concomitant therapy is necessary, monitoring of renal function is recommended, particularly in patients with risk factors for renal impairment.