Asunaprevir/Beclabuvir/Daclatasvir (Clinical Trial) + Midazolam = Precautionary

Effect on Concentration

Asunaprevir/Beclabuvir/Daclatasvir (Clinical Trial)
Unknown
Applies within class?
No
Midazolam
Decrease
Applies within class?
No

Pharmacologic Effects

Asunaprevir/Beclabuvir/Daclatasvir (Clinical Trial)
Effect
N/A
Applies within class?
No
Midazolam
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 22-Nov-2022

Summary

According to the study authors, weak to moderate induction of CYP 3A was observed. Co-administration of DCV/ASV/BCV and substrates of CYP 3A4 (including midazolam), should be done with caution, though no specific dose adjustments have been recommended.

Sources

Asunaprevir/beclabuvir/daclatasvir vs many drugs ^

Study Design

Twenty healthy subjects received a probe substrate cocktail containing caffeine 200 mg on day one (alone), on day 16 (with the fixed dose combination of daclatasvir [DCV] 30 mg, asunaprevir [ASV] 200 mg, and beclavubir [BCV ]75 mg), and on day 31 (with the fixed dose combination plus an additional dose of BCV 75 mg twelve hours after the fixed dose combination was given). The fixed dose combination was given on days 6-35, and on days 21-35 an additional 75 mg dose of BCV was given. Serial pharmacokinetic sampling occurred for six days after each probe dose was given.

Study Results

Coadministration of DCV/ASV/BCV with midazolam 5 mg resulted in the following changes in pharmacokinetic parameters. The Cmax GMR of midazolam was 0.57 (90% CI 0.5-0.65) and the AUC GMR was 0.53 (0.47-0.6). Additional doses of BCV had no effect on CYP 3A4. Study medications were well tolerated.

Study Conclusions

References

X Tao, K Sims, Y Chang, J Rana, E Myers, M Wind-Rotolo, et al. Effect of daclatasvir/asunaprevir/beclabuvir in fixed dose combination on the pharmacokinetics of cyp450/transporter substrates in healthy adults. abstract o_6. 17th International Workshop On Clinical Pharmacology Of Hiv And Hepatitis Therapy. Washington DC, USA. ; 2016.