Simeprevir + Efavirenz = Prohibited

Effect on Concentration

Simeprevir
Decrease
Applies within class?
No
Efavirenz
No change
Applies within class?
No

Pharmacologic Effects

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

Interaction History

N/A

Last Updated 22-Nov-2022

Summary

The authors concluded that coadministration of simeprevir and efavirenz is not recommended, because it may result in decreased simeprevir concentrations.

Sources

Simeprevir vs Efavirenz ^

Study Design

Drug-drug interactions with simeprevir were evaluated in a two-panel, randomized, open-label, twoperiod crossover study with a washout period of 7 days between study periods. Nineteen healthy subjects (18 male) received daclatasvir (60 mg once daily) or daclatasvir (60 mg once daily) plus simeprevir (150 mg once daily) for 7 days, and 25 healthy subjects (20 male) received simeprevir (150 mg once daily) or simeprevir (150 mg once daily) plus daclatasvir (60 mg once daily) for 7 days; all treatments were administered under fed conditions.

Study Results

For simeprevir, coadministration resulted in a 71% decrease in exposure (the AUC) in comparison with simeprevir alone. The GMR (with 90% CI), Cmax and AUC of simprevir / efavirenz coadministration compared with simeprevir administration alone were0.49 (0.44 - 0.54), 0.29 (0.26, 0.33), and 0.09 (0.08 - 0.12), respectively. There was no change in efavirenz exposure with coadministration . GMR when comparing efavirenz and simeprevir coadministration to efavirenz administration alone was 0.97 (0.89, 1.06) while AUC and Cmax were 0.9 (0.85, 0.95) and 0.87 (0.81, 0.93) respectively.DrugEffect on PKPK ParametersCmaxAUCCminSimeprevirDecrease0.49 (0.44-0.54)0.29 (0.26-0.33)0.09 (0.08-0.12)EfavirenzNo change0.97 (0.89-1.06)0.9 (0.85-0.95)0.87 (0.81-0.93)

Study Conclusions

References

Sivi Ouwerkerk-Mahadevan, Jan Snoeys, Monika Peeters, Maria Beumont-Mauviel, Alexandru Simion. Drugdrug interactions with the ns3/4a protease inhibitor simeprevir. Clinical Pharmacokinetics. 2016; 2: 197-208.