Use caution when using with TDF containing regimens given the increase in TDF concentrations.
Atazanavir/Ritonavir versus Sofosbuvir/Velpatasvir
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Study Design
Nine cohorts in two phase I, open-label, randomized, multiple-dose cross-over studies in healthy volunteers compared the pharmacokinetics of sofosbuvir/velpatasvir (SOF/VEL) when given alone versus when this fixed dose combination was given with several antiretroviral medications. In the seventh cohort, 24 subjects were given SOF/VEL with a fixed dose combination of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) with Ritonavir boosted Atazanavir (ATV/r). Steady state pharmacokinetic samples were collected over 24 hours on the last day of dosing for each treatment. Geometric Least Square Means Ratios and 90% confidence intervals (combination vs alone) were estimated and compared against a lack of PK alteration boundaries of 70 – 143% for all analyses. Safety of these medications was also evaluated using standard laboratory values and physical examination.
Study Results
Co-administration of SOF/VEL with FTC/TDF plus ATV/r did not appear to impact the exposure to SOF or GS-331007 (the active metabolite of SOF). This did increase the VEL concentrations 142%. There was no significant effect of SOF/VEL on exposures to FTC. An increase in ATV AUC and Cmax was seen, though values were not given. Co-administration of SOF/VEL with TDF containing regimens increased the exposure of TDF by 20-81%.There does not appear to be any impact of SOF/VEL on tenofovir alafenamide (TAF) or tenofovir derived from TAF.
Study Conclusions
According to the authors, there is no pharmacokinetic interaction between SOF/VEL and atazanavir/ritonavir (ATV/r). Despite the increases in AUC and Cmax seen, a previous study (not referenced) describes the concomitant use of ATV/r with 500 mg of velpatasvir, and because there was no increase in adverse events, the authors concluded that no clinically significant interaction would be seen in this circumstance. Concomitant exposure to emtricitabine/tenofovir disoproxil fumarate, led to an increase in tenofovir disoproxil fumarate exposures. However, no guidance has been offered regarding the potential drug interaction between SOF/VEL and tenofovir disoproxil fumarate, and clinical judgement should be utilized.
References
Mogalian E, McNally J, Shen G, Moorehead L, Sajwani K, Smith B, Mathias A. Drug-drug interaction profile of sofosbuvir/velpatasvir fixed-dose combination. Journal Of Hepatology. 2016; 2: S313-S314.
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