Increased International Normalized Ratio in a Patient Taking Warfarin and Celecoxib

Abstract

Objective:

To report a case of increased international normalized ratio (INR) associated with the addition of celecoxib therapy.

Case Summary:

A 77-year-old white woman who was previously stabilized at a target INR of 2–3 on warfarin 26.25 mg/wk for recurrent atrial fibrillation presented with “leg pain.” Celecoxib 100 mg twice daily orally was added to her regimen. After approximately three weeks of celecoxib therapy, her INR was elevated at 3.5, with no signs of bleeding. Her warfarin was withheld for one day and reinitiated at 23.75 mg/wk (∼10% decrease). Follow-up INRs at one and three weeks had returned to target INR range between 2 and 3.

Discussion:

Drug interactions are common with warfarin due to induction or inhibitions of the cytochrome P450 system and changes in protein binding. Although the celecoxib package insert states that there is not a significant interaction in healthy subjects receiving 2–5 mg/d of warfarin, the potential exists, as both are highly protein bound and metabolized through CYP2C9.

Conclusions:

This case report suggests that the INR may be increased after celecoxib initiation in patients undergoing anticoagulation. This may heighten the risk for clinically significant bleeding in patients previously stabilized on a warfarin regimen. Clinicians should consider more frequent INR monitoring of patients receiving warfarin after celecoxib is initiated.