Rilpivirine/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 second cohort, 24 subjects were given SOF/VEL with a fixed dose combination of antiretroviral agents containing rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/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 RPV/FTC/TDF did not appear to impact the exposure to VEL, and 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 RPV, or FTC. Co-administration of SOF/VEL with TDF containing regimens increased the exposure of TDF by 20-81%, and in this arm of the study the TDF exposures increased 40%. 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 significant pharmacokinetic interaction between SOF/VEL and rilpivirine, and coadministration of these agents can be done without concern. 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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