Enzalutamide-warfarin interaction necessitating warfarin dosage adjustment: A case report of successful clinical management

Summary

What is known and objectives

Enzalutamide package labeling recommends avoiding concurrent warfarin use due to potential reductions in warfarin concentrations via enzalutamide-associated hepatic enzyme induction. A case of successful management of this interaction via warfarin adjustments is reported.

Case description

A 77-year-old Caucasian male, previously relatively stable on warfarin 42-45 mg weekly, reported to clinic after the recent start of enzalutamide and subsequent hospitalization with a subtherapeutic International Normalized Ratio (INR). A 50% increase in weekly warfarin dose resulted in a therapeutic INR. Enzalutamide was temporarily discontinued, and a 33% weekly warfarin dose decrease resulted in two therapeutic INRs.

What is new and conclusion

This is the first case to highlight the clinical significance of this interaction, noting that patients taking enzalutamide may require approximately 30%-50% adjustment in their warfarin dosage to maintain a therapeutic INR.

Enzalutamide is a moderate CYP2C9 inducer, which can reduce the plasma concentrations of warfarin via metabolism induction when given concurrently. Although not always clinically feasible, enzalutamide package labeling recommends to avoid this combination due to the narrow therapeutic index of warfarin and the risk of significant INR fluctuations. Our case illustrates that patients receiving this combination can be successfully managed in clinical practice and may require warfarin dosage adjustments of 30-50% to maintain a therapeutic INR.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2x06THU