NSAIDs (nonsteroidal anti-inflammatory drugs) are a group of more than 20 medications that reduce pain, inflammation, and fever. The most familiar examples are ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn), and aspirin. Some are available over the counter, while others require a prescription, and they come in both oral and topical forms.
Common Over-the-Counter NSAIDs
Three NSAIDs are widely sold without a prescription in the United States:
- Ibuprofen (brand names Advil, Motrin): typically taken in 200 to 400 mg doses every four to six hours for mild to moderate pain. For chronic conditions like osteoarthritis or rheumatoid arthritis, doctors may recommend higher daily amounts, up to 3,200 mg divided across the day.
- Naproxen (brand names Aleve, Naprosyn): lasts longer per dose than ibuprofen, so most people take it every 8 to 12 hours instead of every 4 to 6.
- Aspirin: one of the oldest NSAIDs, used for pain relief and also in low doses (81 mg) to help prevent blood clots. Aspirin works differently from other NSAIDs because it permanently disables the enzyme it targets, which is why it has a lasting effect on blood clotting.
Prescription NSAIDs
When over-the-counter options aren’t enough, doctors can prescribe stronger NSAIDs. These include:
- Celecoxib (Celebrex): a selective type that targets inflammation more precisely and tends to cause fewer stomach problems
- Diclofenac: available in both oral and topical forms, commonly used for arthritis and musculoskeletal pain
- Indomethacin: often used for gout flares and certain types of inflammatory arthritis
- Meloxicam: a once-daily option frequently prescribed for osteoarthritis
- Ketoprofen: used for arthritis and general pain
- Etoricoxib: another selective type, available in many countries outside the U.S.
Higher-dose versions of ibuprofen and naproxen are also available by prescription for people who need more than the OTC strength.
Topical NSAIDs
Not all NSAIDs come as pills. Topical versions, applied directly to the skin over a painful joint, include diclofenac gel, ibuprofen cream, ketoprofen gel, and piroxicam. These are particularly useful for localized pain like knee osteoarthritis.
The key advantage is fewer internal side effects. In studies comparing topical diclofenac to the oral version, patients using the topical form experienced significantly fewer gastrointestinal problems: 25% reported GI events compared to 39% on the oral form. Dyspepsia, diarrhea, and abdominal pain were all roughly cut in half. The tradeoff is more skin reactions at the application site. About 29% of topical users experienced dry skin, itching, or contact dermatitis, compared to just 6% of oral users.
How NSAIDs Work
Your body produces substances called prostaglandins whenever tissue is damaged or inflamed. Prostaglandins trigger pain, swelling, and fever. NSAIDs block the enzyme (called cyclooxygenase, or COX) that your body needs to make prostaglandins. Less prostaglandin production means less pain and inflammation.
There are two versions of this enzyme. COX-1 runs all the time and handles everyday functions like protecting the stomach lining and helping blood clot normally. COX-2 ramps up specifically during inflammation. Most traditional NSAIDs, like ibuprofen and naproxen, block both versions. That’s why they relieve pain effectively but can irritate the stomach: they’re also suppressing the enzyme that keeps your stomach protected.
Selective vs. Non-Selective NSAIDs
This distinction matters because it directly affects side effects. Non-selective NSAIDs (ibuprofen, naproxen, indomethacin, diclofenac, ketoprofen) block both COX-1 and COX-2. Selective NSAIDs (celecoxib, etoricoxib) preferentially block COX-2, leaving COX-1 more intact.
The practical difference is significant for your stomach. In comparative research, the selective group was associated with roughly 65% fewer gastrointestinal side effects than the non-selective group. People on selective NSAIDs were also far less likely to stop taking their medication because of stomach problems. If you’ve had ulcers, gastritis, or other GI issues, a selective NSAID may be a better fit.
Risks and Safety Warnings
All non-aspirin NSAIDs carry an FDA black box warning, the most serious type of safety alert, for two categories of risk: cardiovascular events (heart attack and stroke) and gastrointestinal bleeding. The risk increases with longer use and higher doses, which is why guidelines recommend using the lowest effective dose for the shortest time you need it.
People who have had coronary artery bypass surgery should not take NSAIDs. Those with existing heart disease or risk factors for it face higher cardiovascular risk from these drugs. Taking aspirin alongside another NSAID does not reduce the heart risk but does increase the chance of GI bleeding.
NSAIDs During Pregnancy
The FDA warns against NSAID use from 20 weeks of pregnancy onward. These drugs can cause rare but serious kidney problems in the developing baby, leading to dangerously low amniotic fluid levels. After 30 weeks, there’s an additional risk: premature closure of a blood vessel near the baby’s heart that needs to stay open until birth. The one exception is low-dose aspirin (81 mg), which is sometimes specifically recommended during pregnancy for certain conditions like preeclampsia prevention.
NSAIDs vs. Acetaminophen
Acetaminophen (Tylenol) is not an NSAID. It reduces pain and fever but does not reduce inflammation, so it works through a different pathway. For pain that involves swelling, like a sprained ankle or arthritis flare, NSAIDs are generally more effective. For headaches or fever without significant inflammation, acetaminophen works similarly with a different side effect profile: easier on the stomach but harder on the liver at high doses.
The two can be combined. A 2024 American Dental Association guideline recommended NSAIDs alone or combined with acetaminophen as the first choice for managing dental pain in adults and adolescents, noting that the combination can be more effective than either one alone.