Obeticholic Acid + Midazolam = Unknown or no reaction

Effect on Concentration

Obeticholic Acid
No change
Applies within class?
No
Midazolam
Increase
Applies within class?
No

Pharmacologic Effects

Obeticholic Acid
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

Obeticholic Acid versus Midazolam ^

Study Design

In a fixed-sequence and 2-period study in n=24 healthy subjects were given a single oral dose of 2mg midazolam on day 1 and day 19. Obeticholic acid (OCA) 10mg or 25 mg daily alone was given for 13 days prior to the administration of the second midazolam dose.

Study Results

Following multiple doses of OCA 10mg QD, no change in systemic exposures to midazolam was found. Multiple doses of OCA 25mg QD yielded a different response as they increased the midazolam AUC by 26% and the midazolam Cmax by 17%.

Study Conclusions

Per the investigators, dose adjustments of CYP3A substrates is not needed when co-administering OCA 10mg with a CYP3A substrate such as midazolam.

References

Edwards JE, Eliot L, Parkinson A, Karan S, MacConell L. Assessment of pharmacokinetic interactions between obeticholic acid and caffeine, midazolam, warfarin, dextromethorphan, omeprazole, rosuvastatin, and digoxin in phase 1 studies in healthy subjects. Advances In Therapy. 2017; 9: 2120-2138.