Change in Prothrombin Time International Normalized Ratio due to Drug Interaction between Celecoxib and Warfarin

Abstract

Objective: Celecoxib has been reported to enhance the action of warfarin by inhibiting CYP2C9, its major hepatic drug-metabolizing enzyme, but sufficient information about the mechanism has not been obtained, especially in Japan.
Methods: A study was conducted to investigate the prothrombin time international normalized ratio (PT-INR) and the warfarin sensitivity index (WSI) before and after concurrent administration of celecoxib, as well as the Drug Interaction Probability Scale (DIPS) scores to determine causality with drug interactions, in patients commencing concurrent therapy with celecoxib and warfarin at Kanagawa Prefectural Keiyukai Keiyu Hospital during the 4-year period from October 2011 to September 2015.
Results: Analysis of 18 patients showed that the PT-INR increased significantly from 1.53±0.43 before concurrent therapy to 2.18±1.01 after concurrent therapy (p=0.0101).  The WSI also increased significantly from 0.76±0.50 before concurrent therapy to 1.01±0.65 after concurrent therapy (p=0.0044).  According to the DIPS scores, the causal relation was not rated as “Highly Probable” in any of the patients, while it was considered to be “Probable” in 3 patients, “Possible” in 10 patients, and “Doubtful” in 5 patients.
Conclusion: The findings of this study suggested that when celecoxib treatment is initiated in patients who are already taking warfarin, attention must be paid to changes of coagulation profile, especially in elderly patients.