The authors concluded that the combination SOF/VEL/GS-9857 significantly inhibits BCRP transport systems, but has not recommended dose adjustments for the concomitant use of this fixed dose combination and rosuvastatin. Garrison suggested that the data do not support coadministration.
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 rosuvastatin resulted in an increase in rosuvastatin AUC (7.3 fold) and Cmax (18.9 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 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
Pravastatin (OATP substrate) and rosuvastatin (ROSU; BCRP/OATP substrate) AUC were ↑116% and ↑639% respectively when administered with S/V/V; co-use of ROSU with S/V/V is not recommended.
Study Conclusions
Data do not support the co-administration of rosuvastatin and sofosbuvir/velpatasvir/voxilaprevir
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 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
Pravastatin (OATP substrate) and rosuvastatin (ROSU; BCRP/OATP substrate) AUC were ↑116% and ↑639% respectively when administered with S/V/V; co-use of ROSU with S/V/V is not recommended.
Study Conclusions
Data do not support the co-administration of rosuvastatin and sofosbuvir/velpatasvir/voxilaprevir
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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