Simeprevir + Simvastatin = Precautionary

Effect on Concentration

Simeprevir
No change
Applies within class?
No
Simvastatin
Increase
Applies within class?
No

Pharmacologic Effects

Simeprevir
Effect
N/A
Applies within class?
No
Simvastatin
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 18-Jul-2018

Summary

Sources

Simeprevir versus Simvastatin ^

Study Design

In a randomized, open-label, two-panel study, 36 healthy subjects (26 male) received simvastatin (40 mg single doses on days 1 and 13) plus simeprevir (150 mg once daily on days 4–15) under fed conditions.

Study Results

There were no clinically relevant changes in the pharmacokinetics of simeprevir with coadministration of simvastatin. The Cmax and AUC? of simvastatin were also increased with coadministration (by 1.46- and 1.51-fold, respectively) in comparison with simvastatin alone; the Cmax and AUC? of its active metabolite, simvastatin acid, were increased by 3.03- and 1.88-fold, respectively. Drug Effect on PK PK Parameters Cmax AUC Cmin Simeprevir No change Data on File Simvastatin Increase 1.46 (1.17 – 1.82) 1.51 (1.32 – 1.73) NA

Study Conclusions

Given the increase in simvastatin exposure with simeprevir coadministration, titration of the dose of simvastatin to the lowest possible dose, with close monitoring, is recommended by the authors

References

Ouwerkerk Mahadevan S, Snoeys J, Peeters M, Beaumont Mauviel M, Simion A. Drug–drug interactions with the ns3/4a protease inhibitor simeprevir. Clinical Pharmacokinetics. 2016; 2: 197-208.