Simeprevir with Sofosbuvir (Complete Regimen) + Cyclosporine = Precautionary

Effect on Concentration

Simeprevir with Sofosbuvir (Complete Regimen)
No change
Applies within class?
No
Cyclosporine
Decrease
Applies within class?
No

Pharmacologic Effects

Simeprevir with Sofosbuvir (Complete Regimen)
Effect
N/A
Applies within class?
No
Cyclosporine
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 20-Jul-2018

Summary

Sources

Simeprevir/Sofosbuvir versus Cyclosporine ^

Study Design

This was a cohort study in liver transplant patients aged >18 years-old whom had hepatitis C infection before transplantation and whom had HCV recurrence with a detectable HCV RNA before enrollment in the cohort. There were (n=4) subjects in the Sofosbuvir/Simeprevir treatment group, usingSofosbuvir (SOF) 400mg daily with Simeprevir (SIM) 150mg daily. Subjects were administered Cyclosporine (CyA) BID and dosed appropriately to achieve optimal blood concentrations at that time post transplantation. Blood samples were drawn for CyA before SIM and SOF initiation (D0) and at week 4 (W4). Trough concentrations (C0) of CyA at steady state were measured. W4/D0 geometric mean ratio (GMR) and 2 sided 90% confidence interval (CI90) were calculated for Cl/F, this was then compared to the 0.80-1.25 bioequivalence range.

Study Results

For SOF/SMV patients on CyA results showed a GMR of 1.01 with CI90 of (0.68, 1.51)

Study Conclusions

The authors concluded that there was an increased CyA clearance when given together with daily Sofosbuvir andSimeprevir. This increase indicates that liver transplant patients should be given close monitoring during DAA therapy though specifics for dose monitoring or adjustment were not provided. Given the narrow therapeutic window of cyclosporine, use extra precaution when using these drugs concomitantly.

References

Taburet M, Barrail-Tran G, LaForest C, Pageux AP. Effect of direct acting antivirals on the pharmacokinetics of calcineurin inhibitors [abstract 455]. Conference On Retroviruses And Opportunistic Infections. Boston, MA, USA. 2016; February 2016.