Simeprevir + Rifampin = Prohibited

Effect on Concentration

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

Pharmacologic Effects

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

Interaction History

N/A

Last Updated 18-Jul-2018

Summary

Sources

Simeprevir versus Rifampin ^

Study Design

In a phase I, randomized, open-label, three-period crossover study with a washout period of at least 10 days, twenty-one healthy subjects (n = 21; 20 male and one female) received simeprevir (200 mg once daily), rifampin (600 mg once daily) or simeprevir (200 mg once daily) plus rifampin (600 mg once daily; when coadministered, they were given in a fasting state) for 7 days .

Study Results

For simeprevir, coadministration decreased the mean Cmin and AUC24h by 92 and 48 %, respectively, and increased the Cmax by 1.31-fold in comparison with simeprevir alone. Coadministration did not affect rifampin exposure. Drugs Effect on PK PK Parameters Cmax AUC Cmin Simeprevir Decrease 1.31 (1.03 – 1.66) 0.52 (0.41 – 0.67) 0.08 (0.06 – 0.11) Rifampin No change 0.92 (0.8 – 1.07) 1 (0.93 – 1.08) NA

Study Conclusions

The authors concluded that concomitant use of rifampin (RIF; a CYP3A4 inducer) and simeprevir (SMV; a CYP3A4 substrate) is not recommended as it may cause significantly decreased SMV exposures and a loss of therapeutic effect.

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.