Grazoprevir (Single Agent) + Efavirenz = Prohibited

Effect on Concentration

Grazoprevir (Single Agent)
Decrease
Applies within class?
No
Efavirenz
No change
Applies within class?
No

Pharmacologic Effects

Grazoprevir (Single Agent)
Effect
N/A
Applies within class?
No
Efavirenz
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 22-Nov-2022

Summary

Coadministration of EFV and GZR is not recommended as it may lead to subtherapeutic GZR exposure.

Sources

Efavirenz vs grazoprevir ^

Study Design

In an open-label, fixed sequence study, 12 healthy subjects received grazoprevir (GZR, MK-5172) 200mg once daily for 7 days. After 7-day washout, subjects received efavirenz (EFV) 600mg once daily for 14 days, followed by coadministration of GZR 200mg once daily plus EFV 600mg once daily for 7 days.

Study Results

In the presence of steady-state EFV, Pharmacokinetic (PK) parameters of GZR were significantly decreased, presumably due to CYP3A4 induction by EFV. Geometric mean ratios (GMRs; EFV + GZR/GZR) [90% CI] of AUC, Cmax, and C24 for GZR were 0.16 [0.12, 0.28], 0.30 [0.25, 0.37], and 0.12 [0.08, 0.19], respectively.PK of EFV was not significantly impacted when coadministered with GZR. GMRs (EFV+GZR/EFV) [90% CIs] of AUC, Cmax, and C24 for EFV were 1.00 [0.96, 1.05], 0.93 [0.88, 0.98], and 1.03 [0.99, 1.08], respectively.

Study Conclusions

References

Talaty JE, L Caro, W Yeh, et al. Pharmacokinetic interaction between the hcv protease inhibitor mk-5172 and efavirenz in normal healthy volunteers [abstract 492]. 64th Annual Meeting Of The American Association For The Study Of Liver Diseases (aasld). Washington, DC. ; 2013.