Samatasvir + Ritonavir/Simeprevir/TMC647055 = Precautionary

Effect on Concentration

Samatasvir
Increase
Applies within class?
No
Ritonavir/Simeprevir/TMC647055
Increase
Applies within class?
No

Pharmacologic Effects

Samatasvir
Effect
N/A
Applies within class?
No
Ritonavir/Simeprevir/TMC647055
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 22-Nov-2022

Summary

The investigators indicated that concomitant use of samatasvir and simeprevir/TMC647055/ritonavir was well tolerated in healthy subjects. However, close monitoring is recommended until further data is available as PKs of samatasvir were significantly increased when coadministered with simeprevir/TMC647055/ritonavir.

Sources

Simeprevir/tmc647055/ritonavir vs samatasvir ^

Study Design

Healthy subjects (n=32) were randomized to two treatment groups:Group A (n=16): subjects received samatasvir 150 mg once daily for 7 days (Days 1-7), followed by coadministration of samatasvir 150 mg and simeprevir/TMC647055/ritonavir (75/450/30 mg) once daily for 7 days (Days 8-14). PK samples were obtained on Days 8 and 14. Group B (n=16): subjects received simeprevir/TMC647055/ritonavir (75/450/30 mg) once daily for 7 days (Days 1-7), followed by coadministration of samatasvir 150 mg and simeprevir/TMC647055/ritonavir (75/450/30 mg) once daily for 7 days (Days 8-14). PK samples were obtained on Days 8 and 14.

Study Results

1. Coadministration of simeprevir/TMC647055/ritonavir (75/450/30 mg) once daily and samatasvir 150 mg once daily for 7 days in healthy subjects resulted in significantly increased samatasvir pharmacokinetic (PK) parameters.Geometric mean ratios (GMRs; simeprevir/TMC647055/ritonavir + samatasvir / samatasvir) [90% CIs] of samatasvir were: 2.65 [2.53, 2.78] for Cmax and 2.79 [2.61, 2.99] for AUC2. Co-administration of samatasvir slightly increased PK parameters of both simeprevir and TMC647055, whereas no effect on ritonavir PK parameters. GMRs (simeprevir/TMC647055/ritonavir + samatasvir / simeprevir/TMC647055/ritonavir) [90% CIs] of simeprevir were: 1.31 [1.17, 1.46] for Cmax and 1.28 [1.16, 1.40] for AUCGMRs (simeprevir/TMC647055/ritonavir + samatasvir / simeprevir/TMC647055/ritonavir) [90% CIs] of TMC647055 were: 1.14 [1.03, 1.26] for Cmax and 1.20 [1.11, 1.29] for AUCGMRs (simeprevir/TMC647055/ritonavir + samatasvir / simeprevir/TMC647055/ritonavir) [90% CIs] of ritonavir were: 0.982 [0.865, 1.11] for Cmax and 0.996 [0.915, 1.08] for AUC

Study Conclusions

References

X-J Zhou, K Pietropaolo, D Frank, et al. Pharmacokinetics and drug-drug interaction between samatasvir, an ns5a inhibitior, and co-administered simeprevir, an ns3/4a protease inhibitor, and low dose ritonavir-boosted tmc647055, a non-nucleos. The American Association For The Study Of Liver Diseases 65th Annual Meeting. Boston, MA. ; 2014.