Darunavir/Ritonavir + Sofosbuvir/Velpatasvir = Unknown or no reaction

Effect on Concentration

Darunavir/Ritonavir
Increase
Applies within class?
No
Sofosbuvir/Velpatasvir
Decrease
Applies within class?
No

Pharmacologic Effects

Darunavir/Ritonavir
Effect
N/A
Applies within class?
No
Sofosbuvir/Velpatasvir
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 18-Jul-2018

Summary

Sources

Darunavir/Ritonavir versus Sofosbuvir/Velpatasvir ^

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 eighth cohort, 30 subjects were given SOF/VEL with a fixed dose combination of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) with Ritonavir boosted darunavir (DRV/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 DRV/r did not appear to impact the exposure to VEL, or GS-331007 (the active metabolite of SOF). Exposure to SOF decreased 28%. There was no significant effect of SOF/VEL on exposures to FTC or DRV. Co-administration of SOF/VEL with TDF containing regimens increased the exposure of TDF by 20-81%, and in this particular arm exposures were increased by 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 darunavir/ritonavir (DRV/r). 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.