Adverse and Hypersensitivity Reactions to Prescription Nonsteroidal Anti-Inflammatory Agents in a Large Health Care System

Abstract

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used medications in the United States. NSAID use can be limited by adverse drug reactions (ADRs), including hypersensitivity reactions (HSRs).

Objective: We aimed to use electronic health record data to determine the incidence and predictors of HSRs to prescription NSAIDs.

Methods: We performed a retrospective cohort study of all adult outpatients in a large health care system prescribed diclofenac, indomethacin, nabumetone, or piroxicam between January 1, 2004, and September 30, 2012. The primary outcome was an ADR or HSR attributed to the prescribed NSAID within 1 year of prescription, determined from a longitudinal allergy database. We used natural language processing to classify known ADRs as either HSRs or side effects. Multivariable logistic regression models were used to identify independent risk factors for NSAID HSRs.

Results: Of 62,719 patients prescribed NSAIDs, 1,035 (1.7%) had an ADR, of which 189 (18.3%) were HSRs. Multivariable regression analysis identified that patients with prior drug HSR history (odds ratio [OR] 1.8 [95% CI 1.3, 2.5]), female sex (OR 1.8 [95% CI 1.3, 2.4]), autoimmune disease (OR 1.7 [95% CI 1.1, 2.7]), and those prescribed the maximum standing NSAID dose (OR 1.5 [95% CI 1.1, 2.0]) had increased odds of NSAID HSR.

Conclusions: NSAID therapeutic use can be limited by ADRs; about 1 in 5 NSAID ADRs is an HSR. Both patient and drug factors contribute to HSR risk and are important to guide patient counseling.

Keywords: Adverse reaction; Allergy; Drug; Hypersensitivity; Side effect.