Obeticholic Acid + Warfarin = Precautionary

Effect on Concentration

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

Pharmacologic Effects

Obeticholic Acid
Effect
N/A
Applies within class?
No
Warfarin
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 20-Jul-2018

Summary

Sources

Obeticholic Acid versus Warfarin ^

Study Design

In a fixed-sequence and 2-period study in n=22 healthy subjects were given a single oral dose of 25mg of warfarin on day 1 and day 21. Obeticholic acid (OCA) 10mg or 25 mg daily alone was given for 13 days prior to the administration of the second warfarin dose.

Study Results

Following multiple doses of OCA 10mg QD, AUC and Cmax of S-warfarin increased by 13% and 12% respectively. INR was also measured during the study, the maximum INR decreased by 11.1% while the accumulative INR in 24 hours decreased by 3.3%. Following multiple doses of OCA 25mg QD, AUC and Cmax of S-warfarin increased by 18% and 6% respectively. The maximum INR decreased by 7.2% while the accumulative INR in 24 hours decreased by 1.8%.

Study Conclusions

Per the investigators, therapeutic monitoring of warfarin should be implemented when OCA is co-administered with warfarin. monitoring and maintenance of target INR range are required during coadministration of OCA with drugs that are metabolized by CYP1A2 (R-warfarin).

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.