Elbasvir/Grazoprevir + Cyclosporine = Prohibited

Effect on Concentration

Elbasvir/Grazoprevir
Increase
Applies within class?
No
Cyclosporine
No change
Applies within class?
No

Pharmacologic Effects

Elbasvir/Grazoprevir
Effect
N/A
Applies within class?
No
Cyclosporine
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 22-Nov-2022

Summary

Concomitant administration of GZR/EBR with CsA is not recommended.

Sources

Grazoprevir/elbasvir vs tacrolimus, mycophenolate mofetil, prednisone, or cyclosprine ^

Study Design

This was a 4-part, open label, mulitple site study. Each part consisted of 2 periods with a fixed sequence design. In Part 2, the pharmacokinetic (PK) interaction potential between grazoprevir/elbasvir (GZR/EBR) and tacrolimus (TAC) was studied.16 healthy adults were given a single dose of TAC 2mg on Day 1 (Period 1). After a 6-day washout, subjects took GZR/EBR 200/50mg once daily for 16 days, with administration of TAC 2mg on Day 11 in Period 2.

Study Results

Using geometric mean ratios and 90% confidence intervals (GMR, 90% CI), results showed a clinically relevant 15-fold increasein AUC for GZR, and a 2-fold increasein AUC for EBR when co-administered with single-dose CsA.GRZ/EBR had no significant effect on the PK exposure of CsA.PK ParameterGZR/EBR + CsA / CsAGMR (90% CI)GZR/EBR + CsA / GZRGMR (90% CI)GZR/EBR + CsA / EBRGMR (90% CI)AUC0.96 [0.90, 1.02]15.21 [12.83, 18.04]1.98 [1.84, 2.13]Cmax0.90 [0.85, 0.97]17.00 [12.94, 22.34]1.95 [1.84, 2.07]Cmin1.00 [0.92, 1.08]3.39 [2.82, 4.09]2.21 [1.98, 2.47]

Study Conclusions

References

Yeh WW, H Feng, L Caro, et al. Clinically meaningful pharmacokinetic interactions between hcv inhibitors grazoprevir/elbasvir with tacrolimus, mycophenolate mofetil, and prednisone, but cyclosprine increases grazoprevir/elbasvir ex. 66th Annual Meeting Of The American Association For The Study Of Liver Diseases (aasld). San Francisco, CA. ; 2015.