Risk Factors of Drug Interaction between Warfarin and Nonsteroidal Anti-Inflammatory Drugs in Practical Setting

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to interact with the oral anticoagulant warfarin and can cause a serious bleeding complication. In this study, we evaluated the risk factors for international normalized ratio (INR) increase, which is a surrogate marker of bleeding, after addition of an NSAID in a total of 98 patients who used warfarin. Patient age, sex, body mass index, maintenance warfarin dose, baseline INR, coadministered medications, underlying diseases, and liver and kidney functions were evaluated for possible risk factors with INR increase ≥15.0% as the primary end-point. Of the 98 patients, 39 (39.8%) showed an INR elevation of ≥15.0% after adding a NSAID to warfarin therapy. Multivariate analysis showed that high maintenance dose (>40 mg/week) of warfarin (P=0.001), the presence of coadministered medications (P=0.024), the use of meloxicam (P=0.025) and low baseline INR value (P=0.03) were the risk factors for INR increase in respect to NSAID-warfarin interaction. In conclusion, special caution is required when an NSAID is administered to warfarin users if patients are taking warfarin >40 mg/week and other medications interacting with warfarin.

Effect of single-dose extended-release oral azithromycin on anticoagulation status in warfarinized patients

“…The infection itself (inflammatory syndrome) may alter the warfarin metabolism or hepatic clotting factor synthesis 2,3) . Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to interact with the oral anticoagulant warfarin and can cause serious bleeding complications 11,12) , although the results of this study failed to show significant relationship between the dose of NSAIDs and INR value.…”

Impact of Aspirin on Warfarin Control as Measured by Time in Therapeutic Range

“…Similar to this, Choi et al . . showed that almost 40% of patients on warfarin had an INR increase after initiation of a NSAID with the highest risk from meloxicam and lower risk from naproxen, celecoxib and ibuprofen.…”

Drug–Drug Interactions in Headache Medicine

“…In one study, it was shown that the risk of using NSAIDs is higher in patients who are on >40 mg/week of warfarin . Although generally the combined use of NSAIDs with anticoagulant agents is discouraged, this study was conducted on patients who were using NSAIDs daily.…”

“…In one study, it was shown that the risk of using NSAIDs is higher in patients who are on >40 mg/week of warfarin. 6 Although generally the combined use of NSAIDs with anticoagulant agents is discouraged, this study was conducted on patients who were using NSAIDs daily. Since in headache medicine NSAIDs are typically used on an "as needed" basis (except in some uncommon headache disorder such as hemicrania continua), there are no supporting data for recommendations on how to readjust the anticoagulant dose (specifically warfarin) in the setting of daily NSAID use.…”