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Allergic to NSAIDs? Use These Medications Instead

Cartoon woman with an allergic reaction

Like millions of people, you have probably used an NSAID on more than one occasion before to relieve common aches and pains such as back pain, headache, fever, or stiffness and swelling during an arthritis flare. 

Nonsteroidal antiinflammatory drugs (NSAIDs) are widely available medications used to relieve pain and inflammation. They are available by prescription and over the counter. Examples of common over the counter NSAIDs include aspirin (Anacin, Excedrin), ibuprofen (Advil, Motrin), and naproxen sodium (Aleve). 

However, hypersensitivity reactions to NSAIDs occur in a small number of people (approximately 2% of the population). The risk of NSAID allergy is higher in people with asthma, nasal polyps, and chronic urticaria (hives). 

So, what medications can people with an NSAID allergy take instead? And do people with NSAID hypersensitivity need to avoid all NSAIDs or just specific drugs? Please continue reading to find out.

Understanding how nonsteroidal anti-inflammatory drugs work

Nonsteroidal anti-inflammatory drugs (NSAIDs) work by blocking an enzyme called cyclooxygenase (COX) in the body. There are two types of COX enzymes: COX-1 and COX-2. These enzymes are necessary for the production of compounds called prostaglandins. Prostaglandins are key mediators of reactions such as pain, inflammation, and fever. Therefore, blocking the COX enzymes will reduce pain and inflammation. 

There are different types of nonsteroidal anti-inflammatory drugs. Non-selective NSAIDs block both COX-1 and COX-2. Other NSAIDs selectively block COX-1 or COX-2.

  • Non-selective NSAIDs: Ibuprofen (Motrin, Advil)
  • COX-1 selective NSAIDs: Aspirin, indomethacin (Indocin), naproxen (Aleve, Naprosyn)
  • COX-2 selective NSAIDs: Celecoxib (Celebrex), diclofenac (Voltaren), meloxicam (Mobic)

Blocking of COX-1 is believed to be primarily responsible for the adverse reactions associated with NSAIDs, including most hypersensitivity reactions. This leads to a decrease in prostaglandins and an increase in leukotrienes which play a key role in allergic symptoms. 

On the other hand, blocking COX-2 is responsible for the anti-inflammatory effects of NSAIDs.

In people with allergic reactions to nonsteroidal anti-inflammatory drugs (NSAIDs), doctors first see what type of adverse reactions are present based on the patient’s medical history. Once an adverse reaction is determined to be an NSAID hypersensitivity reaction, doctors then determine whether the patient is allergic to a single NSAID or all NSAIDs. 

A definitive diagnosis of NSAID hypersensitivity is made based on blood tests, skin tests, and provocation tests (the suspected drug is given by mouth in increasing doses over the course of a day under the supervision of a doctor).

Types of allergic reactions or hypersensitivity reactions to NSAIDs

An allergic reaction to nonsteroidal anti-inflammatory drugs can manifest in various ways.

Cutaneous reactions

Symptoms include skin itching, flushing, urticaria (hives or itchy red welts), and angioedema (swelling below the skin surface due to fluid accumulation). These skin reactions can occur in people with no underlying skin problems. On the other hand, worsening of chronic urticaria can occur in people who already have this condition. Rarely, a severe skin reaction called toxic epidermal necrolysis can occur in which there is blistering and peeling of the skin due to an NSAID drug reaction.

Respiratory symptoms

Respiratory reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) include symptoms such as blocked nose, runny nose, sneezing, cough, bronchospasm (asthma), and difficulty breathing. 

Aspirin exacerbated respiratory disease (AERD)

AERD, also called Samter’s Triad or Aspirin Triad, is a medical condition with three distinctive features: sinus disease with recurrent nasal polyps, asthma, and aspirin allergy or sensitivity to other non-steroidal anti-inflammatory drugs blocking the COX-1 enzyme. 


This is a severe and potentially life-threatening, generalized allergic reaction. Symptoms of this reaction include swelling of the lips, eyes, or tongue, shortness of breath, difficulty swallowing, and fast heart rate. Patients can go into anaphylactic shock from allergic reactions, presenting with a severe drop in blood pressure, even loss of consciousness.

What can I use instead of NSAIDs?

In NSAID-sensitive patients who need to avoid aspirin or other non-aspirin NSAIDs due to allergic reactions, acetaminophen (Tylenol) is generally a safe alternative for relieving pain. This over-the-counter medication is an effective fever reducer and pain reliever. However, a single dose of acetaminophen should be less than 1,000 mg to prevent blocking of the COX-1 enzyme. This is especially true for patients with a sensitivity to aspirin, especially those with aspirin-exacerbated respiratory disease (AERD).

What pain medication can I take if I am allergic to NSAIDs?

If you are allergic to one type of NSAID, your doctor may try you on other NSAIDs. For instance, if you have an aspirin allergy (aspirin is a COX-1 inhibitor), it may be possible to relieve pain using COX-2 inhibitors like celecoxib (Celebrex), diclofenac (Voltaren), and meloxicam (Mobic) without causing adverse effects. However, there can be cross-reactivity between NSAIDs, so your doctor will likely administer a test dose in their office. 

Another option for patients with NSAID sensitivity, specifically aspirin sensitivity, is aspirin desensitization, which involves giving patients aspirin in small incremental doses. This is done when there is a compelling need for aspirin therapy, such as the need to use aspirin long-term to prevent cardiovascular disease. Aspirin desensitization is also useful for patients with ischemic heart disease or chronic arthritis. This is believed to gradually decrease the release of inflammatory compounds from mast cells.

Another option for relieving pain in people with adverse effects from NSAIDs is opioid drugs such as hydrocodone (Vicodin) and oxycodone (OxyContin). These drugs control pain in a completely different way than NSAIDs by binding to opioid receptors in the nervous system. However, opiates are reserved as the last line of treatment for chronic pain due to the dependence risk. 

Are there anti-inflammatory drugs that are not NSAIDs? What anti-inflammatory can I take if I'm allergic to ibuprofen?

Corticosteroids (steroid hormones), glucocorticoids specifically, are powerful anti-inflammatory drugs. They are commonly used to treat inflammatory conditions such as osteoarthritis, rheumatoid arthritis, bronchitis, asthma, colitis, and allergic skin rashes. However, corticosteroids can have many serious side effects, especially when used at high doses or for long periods of time.

Wrapping Up

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in people of all ages to treat pain, inflammation, and fever. Allergy or hypersensitivity to NSAIDs can manifest as cutaneous reactions (hives, swelling), respiratory reactions (breathing trouble, runny nose, blocked nose), or a serious and potentially life-threatening allergic reaction called anaphylaxis. There are various options to manage pain and inflammation in people who develop allergic reactions to an NSAID, including other NSAIDs and other drugs like acetaminophen, opioids, and steroids. If you cannot take aspirin or other NSAIDs, you should work with your health professional to identify to which drugs the reaction occurs and then discuss a possible alternative treatment option.


  1. https://www.practicalpainmanagement.com/treatments/pharmacological/non-opioids/special-report-return-nsaids
  2. https://my.clevelandclinic.org/health/drugs/11086-non-steroidal-anti-inflammatory-medicines-nsaids
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004000/