The authors concluded that the combination SOF/VEL/GS-9857 inhibits P-glycoprotein, but has not recommended dose adjustments for the concomitant use of this fixed dose combination and dabigatran.
Sofosbuvir/velpatasvir/voxilaprevir vs dabigatran, pravastatin, or rosuvastatin
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Study Design
In an open label, single and multiple dose, two cohort study, healthy subjects (n=36) were administered a single dose of dabigatran etexilate 75 mg alone or in combination with steady state (at least seven days) sofosbuvir(SOF)/Velpatasvir(VEL)/GS-9857 plus GS-9857 100 mg x 1 dose with food. Safety of this study was assessed using routine clinical and laboratory monitoring. Serial blood levels were collected for 96 hours after administration of the probe drugs for PK analysis. Geometric Means Ratios and 90% Confidence Intervals were estimated for AUC and Cmax of probe drugs and compared against pre-specified lack of PK alteration boundaries of 70% - 143%
Study Results
The combination of SOF/VEL/GS-9857 and dabigatran resulted in an increase in total dabigatran AUC (2.6 fold) and Cmax (2.9 fold), and increases in free dabigatran AUC (2.2 fold) and Cmax (2.3 fold).
References
Kirby BJ, J Taylor, Stamm LM, H Wei, D Alhelawe, Ling KHJ, A Mathias, et al. Evaluation of transporter mediated drug-drug interactions with the hcv combination regimen sofosbuvir/velpatasvir/gs-9857 and phenotypic probe drugs. 17th International Workshop On Clinical Pharmacology Of Hiv And Hepatitis Therapy. Washington DC, USA. ; 2016.
Sofosbuvir/Velpatasvir/Voxilaprevir versus Dabigatran Garrison study
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Study Design
The Phase 1 program evaluated DDIs between sofosbuvir/velpatasvir/voxilaprevir (S/V/V) and drug transporter and CYP probes, immunosuppressants, HIV antiretrovirals (ARV), and oral contraceptives (OC). S/V/V 400/100/ 100 mg ± VOX 100 mg was administered to healthy volunteers to achieve systemic VOX exposures observed across the HCV-infected patient population, as appropriate.
Study Results
Total dabigatran AUC was ↑161% following administration of S/V/V with dabigatran etexilate (P-gp substrate).
Study Conclusions
The authors concluded that caution should be used when using dabigatran with S/V/V. dose adjustments may be warranted with clinical monitoring for safety or efficacy.
References
Garrison KL, Kirby B, Stamm LM, Ma G, Vu A. Drug-drug interaction profile of sofosbuvir/velpatasvir/voxilaprevir fixed-dose combination. Ilc: International Liver Conference. Amsterdam, Netherlands. 2017; April 2017.
Sofosbuvir/Velpatasvir/Voxilaprevir versus Dabigatran Garrison study
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Study Design
The Phase 1 program evaluated DDIs between sofosbuvir/velpatasvir/voxilaprevir (S/V/V) and drug transporter and CYP probes, immunosuppressants, HIV antiretrovirals (ARV), and oral contraceptives (OC). S/V/V 400/100/ 100 mg ± VOX 100 mg was administered to healthy volunteers to achieve systemic VOX exposures observed across the HCV-infected patient population, as appropriate.
Study Results
Total dabigatran AUC was ↑161% following administration of S/V/V with dabigatran etexilate (P-gp substrate).
Study Conclusions
The authors concluded that caution should be used when using dabigatran with S/V/V. dose adjustments may be warranted with clinical monitoring for safety or efficacy.
References
Garrison KL, Kirby B, Stamm LM, Ma G, Vu A. Drug-drug interaction profile of sofosbuvir/velpatasvir/voxilaprevir fixed-dose combination. Ilc: International Liver Conference. Amsterdam, Netherlands. 2017; April 2017.
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