Glecaprevir/Pibrentasvir + Midazolam = Unknown or no reaction

Effect on Concentration

Glecaprevir/Pibrentasvir
No change
Applies within class?
No
Midazolam
Increase
Applies within class?
No

Pharmacologic Effects

Glecaprevir/Pibrentasvir
Effect
N/A
Applies within class?
No
Midazolam
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 20-Jul-2018

Summary

Sources

Glecaprevir/Pibrentasvir versus Midazolam ^

Study Design

This was an open label study conducted in (n=12) healthy adult subjects to assess the potential for CYP mediated drug-drug interactions after administration of a CYP probe substrate and the direct acting antiviral combination of ABT-493/ABT-530. On days 1 and 11 of the study subjects were administered single oral dose of 1mg of midazolam. Subsequently subjects were administered ABT-493 300mg and of ABT-530 120mg daily from days 4-13 of the study. Pharmacokinetic analysis using repeated-measures was performed on days 1 and 11 for the CYP substrates and on day 10 for ABT-493/ABT-530. Safety of the study medications was monitored throughout the study period.

Study Results

Based on central value ratios and 90% confidence intervals, there was an (27%) increase in AUC (1.11-1.45) along with a slight increase in Cmax (3%) (0.91-1.17) of midazolam. Pharmacokinetic parameters for ABT-493/ABT-530 were not reported although exposures were similar to other studies in healthy subjects. This combination was generally well tolerated and no serious adverse events were reported.

Study Conclusions

Per the authors, ABT-493/ABT-530 are weak inhibitors of CYP3A of which midazolam is a substrate. Significant drug-drug interactions are not expected. No dosage adjustment is recommended when the two are co-administered in therapy.

References

Kosloski MP, Dutta S, Pugatch D, Li H, Mensa F, Kort J. Abt-493 and abt-530 combination demonstrated minimal potential for cyp-mediated drug-drug interactions. abstract thu-229. Ilc: International Liver Congress. Barcelona, Spain. 2016; April 2016.