NSAIDs, or nonsteroidal anti-inflammatory drugs, are one of the most widely used classes of medication in the world. The most common ones you’ll recognize from any pharmacy shelf are ibuprofen (sold as Advil and Motrin), naproxen (sold as Aleve), and aspirin. Beyond those, several prescription-strength NSAIDs treat chronic pain and inflammatory conditions. They all work through the same basic mechanism, but they differ in how long they last, how they affect the stomach, and what risks they carry with extended use.
Over-the-Counter NSAIDs
Three NSAIDs are available without a prescription in the United States:
- Ibuprofen (Advil, Motrin) is the most commonly reached-for NSAID. It works quickly, with a short half-life of about 2 hours, meaning you typically need to take it every 4 to 6 hours for ongoing pain relief.
- Naproxen (Aleve, Naprosyn) lasts considerably longer, with a half-life of 12 to 15 hours. That’s why you only need to take it twice a day. It’s often preferred for conditions that cause steady, all-day pain like arthritis or menstrual cramps.
- Aspirin is the oldest NSAID and is still used for pain and fever, though it’s now more commonly taken in low doses for its blood-thinning properties.
Prescription NSAIDs
When over-the-counter options aren’t enough, doctors may prescribe stronger NSAIDs. These vary widely in how long they stay active in your body:
- Meloxicam has a half-life of 15 to 20 hours, making it a once-daily option popular for osteoarthritis and rheumatoid arthritis.
- Diclofenac is a short-acting NSAID (half-life of about 2 hours) available in both oral and topical forms. The topical gel version is notable because it delivers the drug directly to a painful joint while keeping blood levels low.
- Indomethacin (half-life around 4.5 hours) is frequently prescribed for gout flares and certain types of inflammatory pain.
- Piroxicam is one of the longest-acting NSAIDs, with a half-life ranging from 30 to 86 hours. It’s taken once daily but can take longer to clear your system.
- Ketorolac is a powerful NSAID typically used for short-term, severe pain, such as after surgery. It’s not meant for ongoing use.
- Celecoxib (Celebrex) belongs to a special subclass and is discussed below.
Other prescription options include etodolac (half-life of 6 to 7 hours), ketoprofen (2 to 4 hours in standard form), and nabumetone. Your doctor will choose one based on the type of pain, how often you want to take a pill, and your personal risk factors.
How NSAIDs Work
All NSAIDs reduce pain, inflammation, and fever by blocking enzymes called COX-1 and COX-2. These enzymes help your body produce prostaglandins, chemicals that trigger inflammation, swelling, and pain signaling at the site of an injury. By physically blocking these enzymes so that their raw materials can’t get in, NSAIDs dial down the inflammatory response.
The catch is that prostaglandins do more than cause pain. They also protect the lining of your stomach and help regulate blood flow to your kidneys. This is why blocking them comes with trade-offs, particularly in the gut and kidneys.
COX-2 Selective NSAIDs
Most NSAIDs block both COX-1 and COX-2 enzymes. COX-2 selective inhibitors were developed to target only the enzyme most involved in inflammation, with the goal of sparing the stomach-protective effects of COX-1. Celecoxib (Celebrex) is the only COX-2 selective NSAID still on the U.S. market.
Two others, rofecoxib (Vioxx) and valdecoxib (Bextra), were pulled from the market after studies linked them to serious cardiovascular problems. Rofecoxib at high doses showed a fivefold increase in cardiovascular risk. The FDA asked Pfizer to voluntarily remove Bextra in 2005. These withdrawals reshaped how all NSAIDs are evaluated for heart safety.
Digestive Side Effects
The most common side effects of NSAIDs are digestive: heartburn, nausea, and general stomach discomfort. These are mild for most people, but with regular use, NSAIDs can cause more serious damage. They can produce ulcers and bleeding in the upper digestive tract, and they also affect the lower intestines in ways that are often overlooked, causing lesions and, in rare cases, scarring that narrows the intestinal passage.
Even low-dose aspirin regimens are not free from these effects. Enteric-coated or sustained-release formulations, which are designed to dissolve further down the digestive tract, may actually increase the risk of lower intestinal damage. Several factors raise your overall risk of digestive complications: being over 60, having a history of stomach or intestinal problems, taking high doses, or combining NSAIDs with blood thinners or corticosteroids.
Kidney and Heart Risks
An estimated 1 to 5 percent of people who take NSAIDs develop kidney-related side effects. NSAIDs reduce blood flow to the kidneys by suppressing the same prostaglandins that regulate it. In most cases, the effect is mild and reversible once you stop the drug. But prolonged use can occasionally lead to chronic kidney problems. About 25 percent of people on NSAIDs experience some sodium retention, which can show up as mild swelling or a few extra pounds of water weight.
Heart risk is the other major concern. The FDA requires all non-aspirin NSAIDs to carry a prominent warning about an increased risk of heart attack and stroke. This risk can begin within the first weeks of use and grows with higher doses and longer duration. Among individual NSAIDs, diclofenac has been associated with higher cardiovascular risk, while naproxen appears to carry the least heart risk of the group. Ibuprofen falls somewhere in between, with a modest trend toward increased stroke risk. The 2025 guidelines from the American College of Cardiology and American Heart Association recommend avoiding non-aspirin NSAIDs whenever possible for people with known or suspected heart disease.
Topical NSAIDs as a Safer Option
Topical NSAID gels and patches deliver the drug directly through the skin to the underlying joint or muscle. Because the medication stays concentrated near the application site, blood levels remain much lower than with an oral pill. A study published in the Journal of the American Heart Association found that people using topical NSAIDs, even those who already had heart disease, experienced fewer heart attacks, strokes, and other cardiovascular events compared to those taking oral NSAIDs. Topical diclofenac is the most widely available version and works well for localized joint pain, particularly in the knees and hands.
Pregnancy and NSAIDs
The FDA recommends avoiding NSAIDs at 20 weeks of pregnancy or later. After that point, NSAIDs can impair fetal kidney function and reduce the volume of amniotic fluid surrounding the baby. This applies to all NSAIDs, whether prescription or over the counter.