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by Dr. Borenstein M.D. and C.H. Weaver M.D. updated 4/2022

Non-steroidal anti-inflammatory drugs, or NSAIDs, are the most commonly used treatments for osteoarthritis (OA), inflammation, stiffness and related pain. NSAIDs include aspirin, ibuprofen, naproxen and celecoxib. They are available over-the-counter or by prescription and may be taken orally or applied topically to the skin in a cream, lotion or gel form.

NSAIDs are generally safe to use for minor flares of pain, but they do have many possible side effects if you take them for a long time or in high doses. Side effects include bleeding, damage to the kidneys, gastritis/bleeding ulcers, fluid retention and high blood pressure.

What Do We Know About NSAIDS?

NSAIDs block fatty acids made by your body called prostaglandins. These acids, such as COX-1 and COX-2, play a role in inflammation and pain. Some NSAIDs block both COX-1 and COX-2, although COX-1 also helps keep your stomach acid under control. There is one NSAID, celecoxib that only blocks COX-2. It may be gentler on your stomach than other NSAIDs.

The American College of Rheumatology’s (ACR) recommendations regarding NSAIDs for osteoarthritis are as follows:

  • Patients with hand OA should be treated with either topical or oral NSAIDs, topical capsaicin, tramadol, or celecoxib (a COX-2 selective inhibitor).
  • Patients with knee OA should be treated with intermittent dosing of over the counter (OTC) acetaminophen, OTC NSAIDs, and/or OTC nutritional supplements. For those who fail to get symptom relief from any of these treatments, either topical or oral prescription NSAIDs, topical capsaicin, or tramadol should be used.
  • NSAID recommendations for patients with hip OA are similar to those for patients with knee OA except that no recommendations were made for topical NSAIDs due to a lack of clinical data on their benefit or safety at the time the guidelines were published.

The ACR believes that most OA patients benefit from treatment with NSAIDs and that the positive consequences far outweigh potential side effects for most people. Your doctor may change your NSAID dose depending on how severe your symptoms are. Whether or not your doctor recommends that you use NSAIDs continuously will depend on the severity of your symptoms and how often you have them, other diseases you may have and your personal preferences.

Common NSAIDs Available for Treatment of Osteoarthritis

  • Aspirin
  • Ibuprofen (Advil®, Motrin®)
  • Naproxen sodium (Aleve®)
  • Celecoxib (Celebrex®)
  • Diclofenac sodium (Voltaren®)
  • Indomethacin (Indocin®)
  • Ketoprofen (Actron®, Orudis®)
  • Piroxicam (Feldene®)
  • Meloxicam (Mobic®)

Some NSAIDs are available over the counter, generally at lower doses for mild pain. These include aspirin, ibuprofen and naproxen sodium. You can also buy generic or “store brand” versions of these medicines.

For stronger pain, there are higher doses of NSAIDs available by prescription. Some NSAIDs are only available by prescription. Don’t take an over-the-counter NSAID if you’re already taking a prescription NSAID. You could easily take too much medicine and put yourself at high risk for side effects like stomach pain, bleeding, fluid retention or kidney problems.

No one NSAID is more effective than others. It’s up to you and your doctor to decide which one may be right for you to take for your OA pain. Your doctor will decide which NSAID to prescribe based on your personal history of NSAID use, the potential for side effects and other diseases or conditions you may have.

Understanding the Side Effects of NSAIDs

NSAIDs can be unsafe depending on your age and other illnesses that might affect whether you can take NSAIDs. If you have hypertension, diabetes, cardiovascular disease, history of ulcers or any type of kidney problems you may not be able to take even OTC NSAIDs or must be followed very closely by your doctor.

The most common side effect of taking NSAIDs is stomach pain or heartburn. Others include:

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  • Bleeding
  • Kidney problems
  • Raised blood pressure
  • Fluid retention
  • Increased risk of heart attack or stroke
  • Ringing in your ears
  • Lightheadedness or dizziness
  • Headaches
  • Allergic reactions, or liver problems (rarely)

If you notice any of these symptoms, get medical care right away:

  • Vomiting
  • Swollen ankles, hands or feet from fluid retention
  • Black or bloody stool
  • Unusual weight gain

Your risk of side effects goes up if you take higher doses of NSAIDs or take these drugs over long periods of time. Also, people who are older or have a history of ulcers may be at higher risk for stomach problems with NSAID use. Talk to your doctor about your options for managing chronic pain.

Celecoxib and meloxicam treat arthritis pain as effectively as other NSAIDs, but because they only block COX-2 and not COX-1, they may be easier on your stomach. COX-1 is a prostaglandin that protects the lining of your stomach. Celecoxib and meloxicam may ease your pain and reduce risk of stomach pain or ulcers.

If the person with OA is taking low-dose aspirin (325 mg or less per day) for heart protection and the practitioner chooses to use an oral NSAID, the ACR strongly recommends using a nonselective NSAID other than ibuprofen in combination with a proton-pump inhibitor. This recommendation is based, in part, on the FDA warning that the combined use of ibuprofen and low-dose aspirin may render aspirin less effective when used for heart protection and stroke prevention because of a recognized drug-drug interaction.

Monitoring for NSAID Side Effects

Let your doctor know if you have unpleasant side effects like heartburn, stomach pain or fluid retention. Don’t “grin and bear it.” It is important to know that many times bleeding ulcers from NSAIDs have no symptoms at all.You need to be monitored by your physician for any drop in your blood count or darkening of the color of your stools. Your doctor may be able to lower your dose or suggest another medicine for your pain. Don’t try to treat severe stomach pain or heartburn on your own.

Keep up with all of your regular check-ups so you can track your blood pressure and other vital signs while you take NSAIDs. Taken over a long time, these drugs can raise your risk of serious heart problems. If you already have high blood pressure, it’s important to check your blood pressure often and if it is increased you may need to stop or adjust the dose of the NSAID. Increased blood pressure can damage your kidneys and increase your risk for a heart attack or stroke.

How to Prevent or Reduce NSAID Side Effects

If you have side effects from your NSAIDs, such as stomach pain or heartburn, you may be able to add another medicine to lower your stomach acid. There are many drugs called proton pump inhibitors that can reduce your risk of ulcers.

They include:

  • omeprazole (Prilosec®, Prilosec® OTC)
  • lansoprazole (Prevacid®, Prevacid® IV, Prevacid® 24-Hour)
  • dexlansoprazole (Dexilent®, Dexilent Solutab®)
  • rabeprazole (Aciphex®, Aciphex® Sprinkle®)
  • pantoprazole (Protonix®)
  • esomeprazole (Nexium®, Nexium® IV, Nexium® 24 HR)
  • omeprazole/sodium bicarbonate (Zegerid®, Zegerid® OTC)

Some of these can be purchased over the counter and others you may need a prescription.

Some simple ways you may ease NSAIDs’ side effects include:

  • Take the lowest possible dose you need to manage your pain.
  • Take your medicine with food, such as your normal meals or a snack. It should be noted that taking NSAIDs with food will not lower your risk of an ulcer. It may increase the tolerability of the NSAID but it won’t reduce the toxicity.
  • Try coated aspirin instead of uncoated. Please note, this may only increase the tolerability of aspirin and not decrease the risk of an ulcer.
  • Avoid the long-lasting, “once-a-day” NSAIDs, because they stay in your system for a longer time than quick-acting ones.
  • Consider using acetaminophen (Tylenol®) for occasional joint pain instead of NSAIDs. It has some side effect risks too, so talk to your doctor before you take any OTC drug for arthritis pain.
  • Discuss with your doctor the synergistic effect of acetaminophen (Tylenol®) with NSAIDs to allow the minimum NSAID dose possible.