Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate 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 first cohort, 24 subjects were given SOF/VEL with a fixed dose combination of antiretroviral agents containing efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). 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 EFV/FTC/TDF resulted in a 53% decrease in VEL exposure. Antiretroviral therapy does not have a significant impact on SOF or GS-331007 (the active metabolite of SOF). There was no significant effect of SOF/VEL on exposures to EFV, or FTC. 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, the coadministration of velpatasvir with efavirenz is not recommended. 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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