Asunaprevir + Dextromethorphan = Precautionary

Effect on Concentration

Asunaprevir
Unknown
Applies within class?
No
Dextromethorphan
Increase
Applies within class?
No

Pharmacologic Effects

Asunaprevir
Effect
N/A
Applies within class?
No
Dextromethorphan
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 22-Nov-2022

Summary

Caution is advised when co-administering CYP2D6 substrates with asunaprevir. Careful consideration should be made to assess the correct dose adjustment and appropriate follow-up and monitoring.Also be aware that the effect of dextromethorphan on the PK of asunaprevir was not assessed in this study.

Sources

Asunapevir vs many drugs ^

Study Design

Two single sequence studies were conducted to assessthe effectof multiple-dose BMS-650032 (asunaprevir) on the pharmacokinetics (PK) ofa cocktail of cytochrome P (CYP) -450 probes and a P-glycoprotein (P-gp) probe. The study subjects includedhealthy men and women ages 18 to 49 years with a BMI of 18 to 32kg/m2.In studyAI447020 on Days 1 and 11, 19 subjects receivedsingle oral doses of substrates of CYP1A2 (Caffeine 200mg), CYP2D6 (Dextromethorphan30mg), CYP3A4 (Midazolam 5mg), CYP2C9 (Losartan25mg), and CYP2C19 (Omeprazole 40mg) concurrently. On days 2-11, 200mg BID of asunaprevir was given. Blood sampleswere collected for PK analysis through 24h post-dose on Days 1 and 11 for the probe substrates. The geometric mean ratios (GMR) and 90% confidence intervals (90%CI) were calculated to show the magnitude of change during co-administration.

Study Results

Drug NameCmaxGMR (90% CI)AUC GMR (90% CI)Dextromethorphan2.719 (2.097, 3.526)3.942 (3.88, 5.032)Co-administration of asunaprevir and dextromethorphan showed that asunaprevir is a moderate inhibitor of CYP2D6. Asunaprevir increased the Cmaxand AUC of dextromethorphan by 2.7-fold and 3.9-fold, respectively. Studies are ongoing to assess the impact that inhibitors and inducers have on asunaprevir.

Study Conclusions

References

T Eley, D Gardiner, A Persson, et al. Evaluation of drug interaction potential of the hcv protease inhibitor bms-650032 at 200mg twice daily (bid) in metabolic cocktail and p-glycoprotein (p-gp) probe studies in healthy volunteers. 62nd Annual Meeting Of The American Association For The Study Of Liver Diseases. San Francisco, CA. ; 2011.