Ritonavir (as stand alone agent) + Simeprevir = Precautionary

Effect on Concentration

Ritonavir (as stand alone agent)
Increase
Applies within class?
No
Simeprevir
Increase
Applies within class?
No

Pharmacologic Effects

Ritonavir (as stand alone agent)
Effect
N/A
Applies within class?
No
Simeprevir
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 18-Jul-2018

Summary

Sources

Ritonavir versus Simeprevir ^

Study Design

In a phase I, randomized, open-label, twoperiod study with a washout period of at least 7 days, 12 healthy male subjects were administered simeprevir (200 mg once daily on days 1–7) or ritonavir (100 mg twice daily on days 1–15) plus simeprevir (200 mg once daily on days 6–12) under fed conditions.

Study Results

Simeprevir exposure was increased after the ?rst dose in the coadministration group, with increases in the Cmax and AUC24h of 1.30- and 1.83-fold, respectively, in comparison with simeprevir alone. Simeprevir exposure was further increased in subjects who received multiple doses of simeprevir and ritonavir, with increases in the Cmax, AUC24h and Cmin of 4.70-, 7.18- and 14.35-fold, respectively, in comparison with administration of simeprevir alone. Drug Effect on PK PK Parameters Cmax AUC Cmin Simeprevir Increase 4.7 (3.84 – 5.76) 7.18 (5.63 – 9.15) 14.35 (10.29 – 20.01) Ritonavir Increase 1.23 (1.14 – 1.32) 1.32 (1.25 – 1.4) 1.44 (1.3 – 1.61)

Study Conclusions

The authors concluded that coadministration of ritonavir (RTV) and simeprevir (SMV) is not recommended as this may result in significant increase of SMV exposure due to potent CYP3A inhibition by ritonavir. Slight increases in ritonavir concentrations were not considered to be clinically significant.

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.