What is the prevalence of hypersensitivity to naproxen (nonsteroidal anti-inflammatory drug, NSAID)?

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Last updated: April 8, 2025View editorial policy

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From the Guidelines

Naproxen allergies are relatively rare, and the exact prevalence is not well-established, but it is estimated to be less than 1% of the general population. The underlying etiology of naproxen allergic reactions is not fully understood, but it is thought to be related to an IgE-mediated mechanism, although there are limited reports of detection of specific IgE to NSAIDs 1. People who have a history of allergic reactions to aspirin or other NSAIDs are at higher risk of developing a naproxen allergy. Symptoms of a true naproxen allergy can range from mild skin reactions like hives or rashes to severe, potentially life-threatening reactions such as anaphylaxis, which includes difficulty breathing, swelling of the face or throat, and a drop in blood pressure. Some key points to consider when evaluating naproxen allergies include:

  • The clinical pattern of a preceding period of sensitization during which the drug is tolerated suggests an IgE-mediated mechanism 1
  • Any NSAID, including selective COX-2 inhibitors, may be responsible for an allergic reaction 1
  • Management of single NSAID reactors, such as those with a naproxen allergy, is contingent on determining the culprit NSAID and finding alternative options for pain control 1 It's essential to distinguish between true allergic reactions, which involve the immune system, and common side effects of naproxen such as stomach upset, heartburn, or dizziness. If you suspect you have a naproxen allergy, you should stop taking the medication immediately and consult with a healthcare provider who may recommend alternative pain relievers or anti-inflammatory medications that don't belong to the NSAID class.

From the FDA Drug Label

The following are additional adverse experiences reported in < 1% of patients taking naproxen during clinical trials and through postmarketing reports Those adverse reactions observed through postmarketing reports are italicized Body as a Whole: anaphylactoid reactions, angioneurotic edema, menstrual disorders, pyrexia (chills and fever)

  • Naproxen allergy is reported as anaphylactoid reactions in less than 1% of patients taking naproxen during clinical trials and through postmarketing reports 2.
  • This suggests that naproxen allergy is a rare occurrence.

From the Research

Prevalence of Naproxen Allergy

  • The prevalence of naproxen allergy is not well-established, but it is considered a rare occurrence 3.
  • A study published in 2016 reported a case of fixed drug eruption due to selective hypersensitivity to naproxen, with tolerance to other propionic acid NSAIDs 3.
  • Another study published in 2009 discussed hypersensitivity reactions to non-steroidal anti-inflammatory drugs, including naproxen, and noted that cutaneous symptoms are the most frequent, with ibuprofen, naproxen, and diclofenac being common culprit drugs worldwide 4.

Comparison to Other Drug Allergies

  • A national cohort study of Veterans' admissions from 2000 to 2014 found that NSAIDs, including naproxen, were among the most commonly reported allergy drug classes, with a prevalence of 5.1% 5.
  • The same study found that the most commonly reported allergy drug classes were penicillins (13%), opiates (9.1%), and ACE inhibitors (5.7%) 5.
  • A study published in 2020 discussed anaphylaxis, a life-threatening systemic reaction, and noted that medications, including NSAIDs like naproxen, are common triggers 6.

Diagnostic Approach

  • The diagnostic approach for naproxen allergy often involves in vivo diagnostic tests, such as patch testing, and in vitro testing, such as detecting specific IgE antibodies or studying the proliferation of T lymphocytes toward the eliciting drug 4.
  • A study published in 2016 used patch testing and single-blind oral challenge testing to confirm the diagnosis of hypersensitivity to naproxen and study cross-reactivity between NSAIDs of the same group 3.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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