Voxilaprevir + Rifampin = Prohibited

Effect on Concentration

Voxilaprevir
Decrease
Applies within class?
No
Rifampin
Unknown
Applies within class?
No

Pharmacologic Effects

Voxilaprevir
Effect
N/A
Applies within class?
No
Rifampin
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 22-Nov-2022

Summary

The authors concluded that hepatic OATP, CYP3A and P-gP play a significant role in the PK of GS-9857. Rifampin inhibits OATP at single doses, but also induces CYP3A and P-gP with multiple doses. Based upon this data, co-administration of GS-9857 with rifampin cannot be recommended, and future studies will inform dosing recommendations.

Sources

Voxilaprevir vs 5 drugs ^

Study Design

This was an open label, single and multiple dose four cohort study in 98 healthy volunteers. Participants were administered a single dose of GS-9857 100 mg alone or in combination with inhibitors or inducers of drug transporters or CYP isoenzymes. These drugs included rifampin 600 mg x 1 dose fasted, or rifampin 600 mg daily for seven days fed. Geometric means ratios and 90% Confidence Intervals for GS-9857 were estimated and compared to pre-specified lack of PK alteration boundaries 70% - 143%. Safety was assessed by routine laboratory and clinical monitoring. Five subjects discontinued the study drug during the study period.

Study Results

GS-9857 concentrations were significantly increased by single doses of rifampin (AUC 7.9 fold, Cmax 11 fold). Multiple doses of rifampin also significantly reduced GS-9857 exposure (AUC 73%, Cmax unchanged).

Study Conclusions

References

Kirby BJ, J Taylor, Stamm LM, Q Song, Y Li, A Mathias. Evaluation of pan genotypic hcv ns3/4a protease inhibitor gs-9857 as the object of transporter and cytochrome p450 mediated drug-drug interactions. 17th International Workshop On Clinical Pharmacology Of Hiv And Hepatitis Therapy. Washington, DC, USA. ; 2016.