Based on theoretical considerations darunavir/cobicistat is expected to increase tenofovir plasma concentrations (P-glycoprotein inhibition). Darunavir/cobicistat and tenofovir disoproxil fumarate can be used without dose adjustments. Monitoring of renal function may be indicated when darunavir/cobicistat is given in combination with tenofovir disoproxil fumarate, particularly in patients with underlying systemic or renal disease, or in patients taking nephrotoxic agents. Cobicistat has been shown to decrease estimated creatinine clearance due to inhibition of tubular secretion of creatinine. Darunavir/cobicistat should not be initiated in patients with creatinine clearance less than 70 ml/min if any co-administered agent (e.g. tenofovir disoproxil fumarate) requires dose adjustment based on creatinine clearance. There are currently inadequate data to determine whether co-administration of tenofovir disoproxil fumarate and cobicistat is associated with a greater risk of renal adverse reactions compared with regimens that include tenofovir disoproxil fumarate without cobicistat.

Renal impairment, including cases of acute renal failure and Fanconi syndrome, has been reported when cobicistat, a component of Prezcobix, was used in an antiretroviral regimen that contained tenofovir DF. Co-administration of darunavir/cobicistat and tenofovir DF is not recommended in patients who have an estimated creatinine clearance below 70 mL/min.  Document urine glucose and urine protein at baseline and perform routine monitoring of estimated creatinine clearance, urine glucose, and urine protein during treatment when darunavir/cobicistat is used with tenofovir DF. Measure serum phosphorus in patients with or at risk for renal impairment when used with tenofovir DF. Co-administration of darunavir/cobicistat and tenofovir DF in combination with concomitant or recent use of a nephrotoxic agent is not recommended. Clinically relevant drug-drug interactions have not been observed or are not anticipated with concomitant use of darunavir and cobicistat with tenofovir-DF.