⚠ Emergency:
If you have taken an NSAID and are experiencing chest tightness, shortness of breath, throat tightening, or severe worsening of asthma — use your adrenaline auto-injector if prescribed and call 999 immediately.
Contents
Why Reactions Happen — The COX-1 Mechanism
Aspirin and most non-steroidal anti-inflammatory drugs (NSAIDs) work by inhibiting the COX-1 and COX-2 enzymes, which the body uses to produce prostaglandins — chemicals involved in pain, fever, inflammation, and tissue protection.
In people with NSAID hypersensitivity, inhibition of COX-1 triggers an imbalance in arachidonic acid metabolism. When COX-1 is blocked, the body produces a surge of pro-inflammatory cysteinyl leukotrienes (CysLTs) that cause bronchoconstriction, nasal congestion, urticaria, and angioedema. This mechanism is:
Pharmacological, not immunological
This is not a true IgE-mediated allergy. There are no IgE antibodies involved. No allergy test (blood test or skin prick) can diagnose it. That is why the gold standard for diagnosis is a supervised aspirin challenge test.
Class-wide, not molecule-specific
Because the reaction is driven by COX-1 inhibition, it is triggered by any drug that significantly inhibits COX-1 — regardless of its chemical structure. This means that aspirin, ibuprofen, naproxen, diclofenac, and many others will all cause reactions in susceptible individuals, even if they have never taken that specific drug before.
Dose-dependent
The threshold for triggering a reaction varies between individuals. Some people react to very small doses of aspirin; others tolerate low-dose aspirin (75 mg) but react to analgesic doses (300–600 mg). Do not test this yourself — threshold assessment must be done under medical supervision.
Important: If you have been told you have a “selective” reaction — that is, you react to one specific NSAID only but tolerate others — the mechanism is different and may involve genuine IgE-mediated or T-cell-mediated hypersensitivity to that specific molecule. This page primarily addresses cross-reactive NSAID sensitivity. If you are uncertain which pattern applies to you, see your allergy consultant before making any decisions about which NSAIDs are safe.
Which Type of NSAID Reaction Do You Have?
Knowing your reaction pattern determines which medicines to avoid. There are four main clinical phenotypes of NSAID hypersensitivity recognised by the international EAACI/WAO classification:
| Phenotype | Symptoms | Triggers | Action |
|---|---|---|---|
| AERD / NSAID-ERD | Bronchoconstriction, nasal congestion, rhinorrhoea, facial flushing after NSAIDs. Often with nasal polyps & asthma (Samter’s Triad) | All COX-1 inhibiting NSAIDs | Avoid all COX-1 NSAIDs. Paracetamol safe. COX-2 selective only under specialist supervision. See salicylates page. |
| NECD | Worsening of pre-existing chronic urticaria / angioedema after NSAIDs | All COX-1 inhibiting NSAIDs | Avoid all COX-1 NSAIDs during active urticaria. Paracetamol usually safe. Omalizumab for urticaria control may improve NSAID tolerance. |
| NIUA | Urticaria / angioedema in patients without pre-existing chronic urticaria | All COX-1 inhibiting NSAIDs | Avoid all COX-1 NSAIDs. Paracetamol usually safe. COX-2 selective assessed under supervision. |
| Single-drug hypersensitivity | Reaction to one specific NSAID only; other NSAIDs tolerated | That specific NSAID only | Avoid that specific drug. Others may be safe — confirmed only by specialist challenge. Do not assume safety without testing. |
If you are unsure which phenotype applies to you, a formal specialist assessment is essential before making any decisions about which NSAIDs may be safe. A supervised aspirin/NSAID provocation challenge is the only reliable way to determine your threshold and phenotype. Book an assessment →
Medicines to Avoid — Active Ingredients
The following medicines are COX-1 inhibiting NSAIDs that should be avoided by patients with cross-reactive NSAID hypersensitivity (AERD, NECD, or NIUA) unless a specialist has specifically confirmed they are safe for you after formal testing. This list covers the active pharmaceutical ingredients — brand names appear in the next section.
Always check the active ingredient, not just the brand name. Many common over-the-counter products contain these active ingredients. Brand names appear in the next section. If you are ever unsure, ask your pharmacist before taking any new medicine — and always mention your aspirin/NSAID sensitivity.
Common UK Brand Names to Recognise
The same active ingredient is sold under many different brand names. This is not exhaustive — always verify the active ingredient on the label. Brands change and new formulations are introduced regularly.
| Active Ingredient | Common UK Brand Names | Commonly Found In |
|---|---|---|
| Aspirin | Aspirin (own brand), Anadin Original, Disprin, Nu-Seals 75, Angettes 75 | Painkillers, cold/flu remedies, cardiovascular prevention tablets |
| Ibuprofen | Nurofen (all formulations), Brufen, Calprofen (children’s), Cuprofen, Ibugel, Ibuleve, Fenbid, Hedex Ibuprofen, many own-brand “ibuprofen” tablets | Painkillers, anti-inflammatories, cold/flu combination remedies, gels and sports creams |
| Naproxen | Aleve (US name, available online), Feminax Ultra, Naprosyn (prescription), Synflex | Painkillers, period pain remedies, prescription anti-inflammatory |
| Diclofenac | Voltarol (gels, patches, tablets), Diclomax, Econac, Arthrotec (with misoprostol) | Prescription anti-inflammatory, topical gels (also sold OTC), patches |
| Indometacin | Indocid, Rimacid | Prescription only — gout treatment, acute inflammatory conditions |
| Ketorolac | Toradol, Acular (eye drops) | Short-term post-operative analgesia (hospital use); eye drops for inflammation after eye surgery |
| Mefenamic acid | Ponstan | Period pain (prescription); heavy menstrual bleeding |
| Piroxicam | Brexidol, Feldene | Prescription — arthritis, musculoskeletal conditions |
| Ketoprofen | Oruvail, Powergel | Prescription — inflammatory conditions; topical gel |
This list is not exhaustive. Always verify the active ingredient on any new medicine with your pharmacist or on the NHS medicines information website (medicines.org.uk or bnf.nice.org.uk).
Safe Analgesic Alternatives
The good news is that safe analgesic options exist for patients with NSAID hypersensitivity. Your individual threshold and clinical context determines the best choice. Always confirm options with your GP or allergy consultant.
◆ Opioid Analgesics (Under Medical Supervision)
For moderate-to-severe pain where paracetamol alone is insufficient, opioid analgesics are generally safe in NSAID-sensitive patients as they do not inhibit COX-1. These should only be used under appropriate medical prescription and supervision.
- Codeine (often combined with paracetamol — e.g. co-codamol 8/500 or 30/500)
- Tramadol (moderate-to-severe pain; prescription only)
- Morphine, oxycodone (hospital or specialist palliative use)
- Dihydrocodeine (DHC Continus)
Important: Codeine requires a prescription and is subject to restrictions in some settings. It also has risk of dependence and constipation. Discuss appropriate use with your GP.
COX-2 Selective Inhibitors — May Be an Option Under Specialist Supervision Only
COX-2 selective inhibitors should never be taken without prior specialist assessment and, in many cases, a supervised provocation challenge. Although they spare COX-1, they are not automatically safe for all NSAID-sensitive patients and carry additional cardiovascular and gastrointestinal risks. This is not a safe substitute that patients can select for themselves.
COX-2 selective inhibitors (coxibs) are NSAIDs designed to preferentially inhibit the COX-2 enzyme while largely sparing COX-1. Because the mechanism of NSAID hypersensitivity involves COX-1 inhibition, COX-2 selective agents may — in many patients — be tolerated. However:
Celecoxib (Celebrex)
A selective COX-2 inhibitor available on prescription. Studies suggest it is tolerated by the majority of NSAID-hypersensitive patients, but a proportion — particularly those with severe AERD — still react. Prior to prescribing, a specialist may perform a supervised celecoxib challenge. Also carries cardiovascular risks: use with caution in patients with heart disease, hypertension, or a history of stroke.
Etoricoxib (Arcoxia)
A highly selective COX-2 inhibitor used in arthritis and acute gout. Generally well tolerated in NSAID-hypersensitive patients when COX-1 is not significantly affected. Cardiovascular contraindications apply. Requires specialist recommendation and challenge before use.
Parecoxib (Dynastat)
An injectable COX-2 inhibitor used for post-operative pain management in hospital. If you are having surgery and standard NSAID analgesics are planned, ensure the anaesthetic and surgical team are aware of your NSAID sensitivity so parecoxib can be discussed as an alternative.
Meloxicam — Not Reliably Safe
Meloxicam is sometimes described as “preferentially COX-2 selective” but inhibits COX-1 significantly at therapeutic doses. It should generally be treated as a standard COX-1 NSAID and avoided in patients with cross-reactive NSAID sensitivity.
Topical NSAIDs — Not Automatically Safe
Topical NSAID products (gels, creams, patches, sprays) are widely available OTC in the UK for muscle, joint, and sports injuries. Many patients assume that because they are applied to the skin rather than swallowed, they are automatically safe — this is not correct.
Systemic absorption occurs
Topical NSAIDs are absorbed transdermally. While systemic levels are lower than oral dosing, they are not zero — particularly when applied over large areas, under occlusive dressings, to broken skin, or when used frequently. There are published case reports of NSAID hypersensitivity reactions — including asthma exacerbations — from topical diclofenac and ibuprofen gels.
Contact allergy risk
Topical NSAIDs can also cause contact sensitisation (allergic contact dermatitis) separately from COX-1-mediated systemic reactions — particularly ketoprofen, which is a known photosensitiser. Patch testing may be needed to distinguish these reactions.
Methyl salicylate rubs
Products such as Deep Heat and similar muscle rubs contain methyl salicylate. While this does not significantly inhibit COX-1, it can be absorbed through the skin in large amounts and has been associated with reactions in highly salicylate-sensitive individuals. Discuss with your consultant if in doubt.
Our advice: Discuss topical NSAID use with your allergy consultant. In many patients with mild NSAID sensitivity, occasional topical use of a low-concentration ibuprofen gel to a small area may be tolerable — but this should be a clinical decision, not an assumption.
Dental & Surgical Procedures — Planning Ahead
Dental procedures and surgery present specific challenges for NSAID-sensitive patients because NSAIDs are commonly used for post-operative pain management and, in hospital settings, may be administered without the patient’s awareness (e.g. as rectal suppositories under anaesthesia, or as routine post-operative analgesics).
Before Dental Treatment
- Tell your dentist about your aspirin/NSAID sensitivity at the start of every appointment — even if you have told them before
- Ask whether any medication planned (injections, painkillers, oral rinses) contains aspirin, ibuprofen, or other NSAIDs
- Paracetamol (with or without codeine) is appropriate for post-extraction or post-procedural pain
- Ibuprofen is widely used for dental pain — request paracetamol as an alternative
Before Hospital Surgery
- Declare your sensitivity clearly in your pre-operative assessment form and verbally to every member of the team
- Request that diclofenac or ketorolac suppositories are not used during or after the procedure
- Ask the anaesthetist and surgical team what NSAIDs are routinely used and confirm alternatives in advance
- Ensure your allergy status is prominently recorded on your hospital wristband and in your medical notes
Low-dose Aspirin for Heart Conditions
If you have been prescribed low-dose aspirin (75 mg daily) for cardiovascular prevention by a cardiologist or GP, do not stop this without discussing with your prescribing doctor first. The cardiovascular benefit must be weighed against the sensitivity risk. Your allergy consultant can liaise with your cardiologist and, in some cases, aspirin desensitisation may be recommended. Do not make this decision alone.
Telling Your Healthcare Team — Who Needs to Know
Aspirin and NSAID sensitivity must be communicated proactively to every healthcare professional who might prescribe or recommend pain relief. Do not assume it is already recorded.
GP
Ensure it is recorded in your medical record and on your medication list
Pharmacist
Ask before buying any OTC painkiller, cold remedy, or skin product
Dentist
Before every appointment — post-procedure analgesics must not contain NSAIDs
Surgeon / Anaesthetist
Before any operation — many standard pain protocols include NSAIDs or aspirin
A&E / Hospital Team
If admitted as an emergency — NSAIDs are frequently given in A&E for pain or fever
Carers & Family
Anyone who might give you medicine or call for help in an emergency
Useful to carry: A written allergy card stating “NSAID / aspirin hypersensitivity — avoid all COX-1 inhibiting NSAIDs including ibuprofen, naproxen, diclofenac, and aspirin. Safe alternatives: paracetamol. For surgical analgesics: discuss COX-2 inhibitor options with specialist.” A MedicAlert bracelet is also recommended for patients at risk of severe reactions.
Quick Safe Medicine Checklist
| Category | ✗ Avoid (cross-reactive sensitivity) | ✓ Usually Safe | ◆ Specialist Advice Needed |
|---|---|---|---|
| Painkillers | Aspirin, ibuprofen, naproxen, diclofenac, all other COX-1 NSAIDs | Paracetamol (standard doses), codeine, tramadol (prescribed), dihydrocodeine | Celecoxib, etoricoxib, parecoxib — only after specialist challenge |
| Cold & Flu Remedies | All products containing aspirin or ibuprofen — check label | Paracetamol-only products (e.g. Panadol Cold & Flu, Lemsip Paracetamol) | Consult pharmacist for any combination remedy |
| Gels & Topical Products | Voltarol gel, Nurofen gel, Ibugel, Ibuleve, ketoprofen gel | Non-NSAID topical analgesics (e.g. capsaicin cream under medical advice) | Deep Heat / methyl salicylate — discuss with consultant |
| Eye Drops | Ketorolac (Acular), bromfenac (Yellox), indometacin drops | Steroid eye drops (dexamethasone, prednisolone), antibiotic drops | Discuss all post-operative eye medications with ophthalmologist |
| Post-Operative Analgesics | Diclofenac suppositories, ketorolac injection, ibuprofen IV | Paracetamol IV, opioids (morphine, fentanyl, oxycodone) | Parecoxib IV — only if discussed with anaesthetist and allergy specialist |
| Dental Products | Bonjela Original (choline salicylate) | Bonjela Teething Gel (no salicylate), Orajel (benzocaine) | Check all OTC dental preparations with pharmacist |
Frequently Asked Questions
Trusted UK Resources
nhs.uk/conditions/nsaids/
NICE CKS — NSAIDs Prescribing →
cks.nice.org.uk
Allergy UK — Aspirin Intolerance →
allergyuk.org
BNF — Check Active Ingredients →
bnf.nice.org.uk
Full NSAID Hypersensitivity & AERD Guide →
privateallergy.uk/salicylates/
Important Notice
This page provides general educational information only and is not a substitute for personalised medical advice. Do not stop any prescribed medication — including low-dose aspirin — without first discussing with your prescribing doctor. Do not test new NSAIDs at home. In a medical emergency, call 999.
References
- Elahi S, Peters AT, Kato A, Stevens WW. Clinical and mechanistic advancements in aspirin exacerbated respiratory disease. J Allergy Clin Immunol. 2025;155(5):1411–1419.
- Magerl M, et al. EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for urticaria. Allergy. 2022;77(3):734–766.
- Foerster U, et al. Importance of aspirin challenges in NSAID-exacerbated respiratory disease. HNO. 2024;72(7):494–498.
- Szatkowski W, et al. What is the next step for patients with AERD: biologics with or without aspirin therapy? Allergy. 2025. doi:10.1111/all.16462
- British National Formulary (BNF). NSAIDs — prescribing information. bnf.nice.org.uk
- NICE Clinical Knowledge Summary. NSAIDs — prescribing issues. cks.nice.org.uk
Page reviewed: June 2026 | London Allergy and Immunology Centre | privateallergy.uk