Nonsteroidal Anti-Inflammatory Drugs

Background

NoteWhat is the prevalence of nonsteroidal anti-inflammatory drug (NSAID) allergy?

In the general population, 1.5 - 3.5% of individuals report an NSAID allergy. However, fewer than 20% of those individuals with self-reported NSAID allergy are consistent with a true hypersensitivity.

NoteWhat are some important therapeutic uses of NSAIDs?

NSAIDs are important for the treatment of acute coronary syndrome, pain treatment, and for certain high-risk pregnancy conditions.

For individuals with chronic back pain, NSAID allergy is a risk factor for increased receipt of opioid prescriptions and development of opioid use disorder.

Management

For non-aspirin exacerbated respiratory disease (AERD) NSAID hypersensitivity, a two-step outpatient NSAID oral challenge has been shown to be a safe and effective approach.

NoteWhat factors are associated with a positive NSAID challenge?

• NSAID reaction within the past 5 years

• Prior immediate reaction within 3 hours of NSAID ingestion

• History of reaction to multiple NSAIDs

• Presence of co-morbid chronic spontaneous urticaria

Oral Challenge

Table 1: Proposed two-step protocol for outpatient NSAID oral challenge in patients without AERD. Adapted from Li et al. (2022)

NSAID	Step 1 Dose (60 minute observation)	Step 2 Dose (120 minute observation)
Aspirin	40.5 mg	325 mg
Ibuprofen	50 mg	500 mg
Naproxen	60 mg	600 mg

Because of the potential future need for higher dose of aspirin for management of acute coronary syndrome, the second dose for aspirin oral challenge is 325 mg instead of 81 mg.

Of the 262 NSAID challenges performed, over 85% had negative challenges. In addition, 76% of patients included in the study reported a history of urticaria, angioedema, or both (Li et al. 2022). For patients experiencing a positive challenge, 45% had their reaction within 3 hours of NSAID ingestion

Li, Lily, Jillian Bensko, Kathleen Buchheit, Rebecca R. Saff, and Tanya M. Laidlaw. 2022. “Safety, Outcomes, and Recommendations for Two-Step Outpatient Nonsteroidal Anti-Inflammatory Drug Challenges.” The Journal of Allergy and Clinical Immunology: In Practice 10 (5): 1286–1292.e2. https://doi.org/10.1016/j.jaip.2021.11.006.