Can a patient take Aspirin (acetylsalicylic acid) if they are allergic to Rofecoxib (Vioxx)?

Can a Patient with Rofecoxib Allergy Take Aspirin?

Yes, a patient with a documented allergy to rofecoxib can safely take aspirin, as rofecoxib is a selective COX-2 inhibitor and aspirin is a COX-1 inhibitor—these represent fundamentally different mechanisms of hypersensitivity with essentially no cross-reactivity. 1

Understanding the Mechanism

The key to answering this question lies in understanding NSAID hypersensitivity phenotypes:

• Rofecoxib is a selective COX-2 inhibitor that was withdrawn from the market but represents a distinct class from aspirin 1
• Aspirin is a potent COX-1 inhibitor with an entirely different mechanism of action 1
• Cross-reactivity patterns in NSAID hypersensitivity occur within COX-1 inhibitors, not between COX-1 and selective COX-2 inhibitors 1

Evidence for Safety

The evidence strongly supports this recommendation:

• Reactions to selective COX-2 inhibitors like rofecoxib are extremely rare in patients with aspirin-exacerbated respiratory disease (AERD), and these drugs can typically be taken safely 1
• Multiple studies demonstrate that rofecoxib does not cross-react with aspirin in patients with various NSAID hypersensitivity patterns 2, 3, 4, 5
• In a study of 60 patients with confirmed aspirin-exacerbated respiratory disease, none reacted to 50 mg rofecoxib (high dose), while all 60 subsequently reacted to aspirin challenge 2
• Among 216 patients with adverse reactions to NSAIDs, only 1 patient (0.46%) reacted to rofecoxib, demonstrating minimal cross-reactivity 4

Clinical Algorithm

If the patient has a documented rofecoxib allergy:

1. Determine the type of reaction to rofecoxib (urticaria, angioedema, anaphylaxis, respiratory symptoms) 1
2. Aspirin can be initiated without challenge in most cases, as cross-reactivity is not expected 1, 2
3. Consider supervised challenge only if:
   • The patient has underlying asthma with nasal polyps (suggesting possible AERD) 1
   • The patient has chronic spontaneous urticaria 1
   • The reaction to rofecoxib was severe anaphylaxis and you want absolute certainty 1

Important Caveats

Common pitfall: Assuming all NSAIDs cross-react with each other 1

• The 2022 Drug Allergy Practice Parameter clearly distinguishes four NSAID hypersensitivity phenotypes, and selective COX-2 inhibitor reactions represent drug-specific hypersensitivity, not cross-reactive patterns 1
• Patients who react to rofecoxib typically have a drug-specific IgE-mediated or T-cell-mediated reaction to that specific molecule, not a COX-inhibition-related reaction 1
• If the patient reacted to multiple structurally unrelated NSAIDs (not just rofecoxib), then reconsider—this suggests a cross-reactive pattern and warrants allergy evaluation before aspirin use 1

Guideline Consensus

The American Academy of Allergy, Asthma, and Immunology suggests that selective COX-2 inhibitors may be used as alternatives in patients with NSAID hypersensitivity, implying the reverse is also true—aspirin can be used in patients with selective COX-2 inhibitor hypersensitivity 1