Asunaprevir + Digoxin = Precautionary

Effect on Concentration

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

Pharmacologic Effects

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

Interaction History

N/A

Last Updated 22-Nov-2022

Summary

Due to the narrow therapeutic index of digoxin, this change in AUC may be clinically significant. Appropriate dose reduction and monitoring should be considered.

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)Digoxin1.087 (0.968, 1.221)1.303 (1.214, 1.398)Asunaprevir increased the AUC of digoxin by 30%. ***Be aware that the effect on asunaprevir PK was not reported in this study.

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.