Potential Interaction between Celecoxib and Warfarin

Abstract

Potential interaction between celecoxib and warfarinTO THE EDITO R : Celecoxib is a recently marketed nonsteroidal antiinflammatory drug with no significant effects on platelet aggregation or serum thromboxane production. 1,2 Although the product monograph 3 states that there is no drug interaction between warfarin and celecoxib, we recently observed a case in which administration of celecoxib to a patient receiving warfarin resulted in a significant increase in the patient's i n t e rnational normalized ratio (INR).Case Report . An 88-y e a r-old white woman with atrial fibrillation, osteoarthritis, glaucoma, hypertension, gout, and hypothyroidism was diagnosed with deep venous thrombosis on June 7, 1999, and prescribed warfarin 5 mg/d. Other medications included furosemide 40 mg/d, levothyroxine 125 µg/d, potassium chloride 10 mEq/d, diclofenac 50 mg and misoprostol 200 µg bid, felodipine 10 mg bid, allopurinol 300 mg/d, digoxin 125 µg/d, metaxalone 400 mg bid, Caltrate-D bid, a multivitamin, and calcitonin nasal spray. The patient was stabilized on warfarin 40 mg/wk (INR 2.7-3.1). Celecoxib 200 mg/d was started on July 8, and diclofenac/misoprostol was stopped (Figure 1). INR prior to starting celecoxib was 3.1. On July 13, the INR was 4.4 and on July 15, the INR further increased to 5.8. The patient experienced no complications, described no changes in dietary habits, and no changes in medication; all other laboratory indices were normal. Wa r f a r i n was withheld for two days and the dosage was reduced to 37.5 mg/wk. The INR decreased to 3.1 on July 20, and increased to 4.1 one week later. At that time, the warfarin dosage was reduced to 32.5 mg/wk. One week later, INR was 3.9, and the dosage was further reduced to 30 mg/wk. INR decreased to 3.0 within one week of this dosage adjustment. The total weekly warfarin dosage was 25% lower than before celecoxib was initiated.

Potential interaction between acenocoumarol and diclofenac, naproxen and ibuprofen and role of CYP2C9 genotype

“…Karim and collegues showed no significant effect of celecoxib on pro-thrombin times or steady-state pharmacokinetics of S-and R-warfarin in a small study with 24 healthy volunteers (31). However, several other reports have been published showing a significant increase in INR after adding celecoxib or rofecoxib, cyclooxygenase-2 selective NSAIDs, to warfarin therapy (32)(33)(34)(35). These results are comparable with our results of acenocoumarol with NSAIDs.…”

Comparison of the incidence rates of thromboembolic events reported for patients prescribed celecoxib and meloxicam in general practice in England using Prescription-Event Monitoring (PEM) data

“…for 10 days) does not inhibit platelet aggregation or prolong bleeding time in studies in healthy volunteers [19]. However, elevated prothrombin times and bleeding episodes have been observed with concomitant use of celecoxib and warfarin [20], and there have been four patients with connective tissue disorders that developed ischaemic complications associated with thrombosis after receiving celecoxib [21][22][23]. Meloxicam (Mobic Õ ), launched in the UK in December 1996, is also considered to be a COX-2 selective inhibitor [24,25], and was indicated for relief of pain and inflammation in rheumatic disease, in exacerbations of osteoarthritic pain and ankylosing spondylitis at launch.…”

Possible International Normalized Ratio Elevation Associated With Celecoxib and Warfarin in an Elderly Psychiatric Patient

“…An open‐label, placebo‐controlled, parallel‐group study in healthy subjects attempted to identify interactions between COX‐2 agents and warfarin 1 . This study concluded that concomitant administration of celecoxib and warfarin did not significantly change the area under the curve, maximum plasma concentration, or prothrombin time (PT), but anecdotal reports of celecoxib‐ and rofecoxib‐associated elevations in PT and international normalized ratio (INR) have been reported 2–5 …”