Patient information: Nonsteroidal antiinflammatory drugs (NSAIDs) (Beyond the Basics)
- Daniel H Solomon, MD, MPH
Daniel H Solomon, MD, MPH
- Matthew H. Liang Distinguished Chair in Arthritis and Population Health
- Professor of Medicine
- Harvard Medical School
- Section Editor
- Daniel E Furst, MD
Daniel E Furst, MD
- Section Editor — Treatment Issues in Rheumatology
- Professor of Rheumatology, University of Washington, Seattle
- Professor of Rheumatology, Washington University of Florence, Florence, Italy
- Professor of Rheumatology, University of California in Los Angeles (Emeritus)
- Director of Research, Pacific
NONSTEROIDAL ANTIINFLAMMATORY DRUG OVERVIEW
Nonsteroidal antiinflammatory drugs (NSAIDs) are medications used to relieve pain and to reduce inflammation. They are some of the most commonly used medications in adults. A variety of NSAIDs are available, including at least 20 in the United States and more elsewhere. Many are available as pills that can be purchased without a prescription ("over-the-counter"), and some are available as topical creams or gels.
Because of the wide availability and frequency of use of NSAIDs, it is important to be aware of their proper use, dose, and potential side effects.
CHOOSING A NONSTEROIDAL ANTIINFLAMMATORY DRUG
It can be difficult to know which NSAID is best for a given individual. In addition, a person’s response to a particular NSAID is hard to predict. If two people take identical drugs and doses, their individual responses may be considerably different. It is sometimes necessary to try one drug for a few weeks and then try a different one to find the optimal NSAID.
A healthcare provider is the most qualified person to help choose an NSAID, although you can assist in the decision-making process.
TOPICAL NONSTEROIDAL ANTIINFLAMMATORY DRUGS
Several NSAIDs are available as creams and gels for topical use (to be applied directly to the skin). These agents have been shown to have similar benefits to taking NSAIDs in pill form in osteoarthritis and low back pain. Topical use may be safer than the pill form.
HOW NONSTEROIDAL ANTIINFLAMMATORY DRUGS WORK
NSAIDs work to reduce pain and inflammation by inhibiting enzymes, called cyclooxygenases (COX). By inhibiting COX, NSAIDs help to prevent and/or reduce pain and inflammation. COX enzyme inhibition is also responsible for many of the side effects of NSAIDs.
TYPES OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS
There are two main types of NSAIDs, nonselective and selective. The terms nonselective and selective refer to different NSAIDs’ ability to inhibit specific types of COX enzymes.
●Nonselective NSAIDs – Nonselective NSAIDs inhibit both COX-1 and COX-2 enzymes to a significant degree.
●Selective NSAIDs – Selective NSAIDs inhibit COX-2, an enzyme found at sites of inflammation, more than the type that is normally found in the stomach, blood platelets, and blood vessels (COX-1).
Nonselective NSAIDs — Nonselective NSAIDs include drugs commonly available without prescription, such as aspirin, ibuprofen (Advil, Motrin, Nuprin), and naproxen (Aleve), as well as many prescription-strength NSAIDs.
Selective NSAIDs — Selective NSAIDs (also called COX-2 inhibitors) are as effective in relieving pain and inflammation as nonselective NSAIDs and are less likely to cause gastrointestinal injury. Celecoxib (Celebrex) is a selective NSAID that is available in the United States. Other selective NSAIDs that can be found elsewhere in the world include etoricoxib (Arcoxia) and lumiracoxib (Prexige).
Selective NSAIDs are sometimes recommended for people who have had a peptic ulcer, gastrointestinal bleeding, or gastrointestinal upset when taking nonselective NSAIDs. Selective NSAIDs have less potential to cause ulcers or gastrointestinal bleeding.
Precautions with selective NSAIDs — Two selective NSAIDs, rofecoxib (brand name: Vioxx) and valdecoxib (brand name: Bextra), were taken off the market in 2004 when it was discovered that people who took these medications had a slightly increased risk of heart attack and stroke.
People with known coronary artery disease (eg, past history of heart attack, angina [chest pain due to narrowed heart arteries], history of a stroke, or narrowed arteries to the brain) and people who are at a higher than average risk for these conditions should avoid using COX-2 inhibitors. Of the nonselective NSAIDs, naproxen may be the safest for people with coronary artery disease, but a clinician should be consulted before use of this or any other NSAID.
NSAIDs are generally not recommended for people with kidney disease, heart failure, or cirrhosis, or for people who take diuretics. Some patients who are allergic to aspirin may be able to take selective NSAIDs safely, although this should be discussed in advance with a healthcare provider.
Dose of NSAIDs — Lower doses of NSAIDs, as recommended for use with nonprescription NSAIDs, are adequate to relieve pain in most people.
If the initial dose of NSAIDs does not improve symptoms, a clinician may recommend increasing the dose gradually or switching to another NSAID. People taking one NSAID should not take a second NSAID at the same time. If low doses of NSAIDs are not fully effective, clinicians may recommend using a higher dose of the NSAID on a regular basis for several weeks to improve the antiinflammatory benefits of these drugs.
NONSTEROIDAL ANTIINFLAMMATORY DRUG SIDE EFFECTS
Most people tolerate NSAIDs without any difficulty. However, side effects can occur. The most notable side effects include the following:
●Cardiovascular system – Blood pressure may rise with use of NSAIDs. Control of treated hypertension may be adversely affected by the addition of either selective or nonselective NSAIDs.
●Gastrointestinal system – Short-term use of NSAIDs can cause stomach upset (dyspepsia). Long-term use of NSAIDs, especially at high doses, can lead to peptic ulcer disease and bleeding from the stomach. (See 'Ulcer disease' below.)
●Liver toxicity – Long-term use of NSAIDs, especially at high doses, can rarely harm the liver. Monitoring the liver function with blood tests may be recommended in some cases.
●Kidney toxicity – Use of NSAIDs, even for a short period of time, can harm the kidneys. This is especially true in people with underlying kidney disease. The blood pressure and kidney function should be monitored at least once per year but may need to be checked more often, depending on a person’s medical conditions. (See 'Kidney disease' below.)
●Ringing in the ears – Ringing in the ears (tinnitus) is common in people who take high doses of aspirin, although it is very uncommon for this to occur in people who take other NSAIDs. The ringing usually resolves when the dose is decreased.
MEDICAL CONDITIONS AND NONSTEROIDAL ANTIINFLAMMATORY DRUGS
People with some medical problems and those taking various medications are at increased risk of complications related to NSAIDs. Potential complications of NSAIDs include the following:
Hypertension — As noted above, the addition of either a selective or a nonselective NSAID to the medications taken by someone with hypertension can result in a loss of blood pressure control. If NSAIDs are required, they should be used at the lowest effective dose and for the shortest duration necessary for the given indication. If chronic use of NSAIDs is anticipated, changes in blood pressure medications may be required.
Cardiovascular disease — Anyone who is at risk for or who has cardiovascular disease (coronary artery disease) may have a further increase in risk of heart attacks when taking an NSAID. This includes people who have experienced a heart attack, angina (chest pain due to narrowed arteries in the heart), procedures to widen clogged arteries, a stroke, or narrowed arteries to the brain. As a result, people who have or who are at high risk for coronary artery disease are generally advised to avoid NSAIDs or, if that is not possible, to take the lowest possible dose of NSAID for the shortest possible time.
Although aspirin is an NSAID, the recommendation to avoid or limit the use of NSAIDs does NOT apply to people who have been advised to take low-dose aspirin to treat or prevent heart attacks or strokes. However, the use of any dose of aspirin plus an NSAID is associated with an increased risk of bleeding. There is also an increased risk of bleeding when NSAIDs are used in patients taking other drugs that reduce clotting, such as anticoagulants (eg, warfarin) or antiplatelet agents (eg, clopidogrel). There is also some concern that nonselective NSAIDs may reduce the cardiovascular benefits of low-dose aspirin. (See 'Interaction with other medications' below.)
Ulcer disease — Those who have had a stomach or intestinal ulcer are at an increased risk of another ulcer while taking an NSAID. People being treated for ulcers should consult their healthcare provider about the safety of taking NSAIDs or drugs containing aspirin. People over 65 years of age have an increased risk of developing ulcers when taking NSAIDs. (See "Patient information: Peptic ulcer disease (Beyond the Basics)".)
Reducing ulcer risk — The risk of developing ulcers can be reduced by taking an anti-ulcer medication in addition to an NSAID. Anti-ulcer agents that reduce gastrointestinal damage from NSAIDs include:
●Inhibitor of stomach acid production – High doses of antacid histamine blockers, such as famotidine (Pepcid), and ordinary doses of the acid production inhibitors, such as omeprazole (Prilosec) or lansoprazole (Prevacid), can reduce the risk of developing an ulcer (related to use of an NSAID).
Bleeding — People who have had bleeding from the stomach, upper intestine, or esophagus have an increased risk of recurrent bleeding when taking NSAIDs.
People with platelet disorders such as von Willebrand disease, abnormal platelet function from uremia, and a low platelet count (thrombocytopenia) are advised to avoid NSAIDs.
Before surgery — Most clinicians recommend stopping all NSAIDs approximately one week before elective surgery to decrease the risk of excessive bleeding. This usually includes aspirin, ibuprofen, naproxen, and most prescription NSAIDs. Specific instructions regarding NSAIDs and surgery should be discussed with the surgeon and with the clinician who prescribed the NSAID.
Interaction with other medications
●Warfarin and heparin – People using anticoagulant medications such as warfarin (brand names: Coumadin, Jantoven) and heparin; a newer anticoagulant such as dabigatran (brand name: Pradaxa), rivaroxaban (brand name: Xarelto), apixaban (brand name: Eliquis) or edoxaban (brand name: Savaysa); or an anti-platelet drug such as clopidogrel (brand name: Plavix), should generally not take NSAIDs or aspirin because of an increased risk of bleeding when both classes of drugs are used. (See "Patient information: Warfarin (Coumadin) (Beyond the Basics)".)
Celecoxib may be safe in such instances but should be used with caution and under the guidance of a clinician.
●Aspirin – As noted above, the combination of low-dose aspirin and an NSAID may increase the risk of bleeding. To preserve the benefit of low-dose aspirin for the heart, aspirin should be taken at least two hours before the NSAID.
●Phenytoin – Taking an NSAID and phenytoin (Dilantin, Phenytek) can increase the phenytoin level. As a result, people who take phenytoin should have a blood test to monitor the phenytoin level when starting or increasing the dose of an NSAID.
●Cyclosporine – People who take cyclosporine (eg, to prevent rejection after an organ transplant or for a rheumatic disease, such as rheumatoid arthritis) should take particular care when taking an NSAID. There is a theoretical risk of kidney damage when cyclosporine and NSAIDs are taken together. To monitor for this complication, blood testing may be recommended.
●People taking one NSAID should not take a second NSAID at the same time because of the increased risk of side effects.
Fluid retention — People with medical conditions that require diuretics, including heart failure, liver disease, and kidney damage, are at increased risk of developing kidney damage while taking nonselective NSAIDs (eg, ibuprofen) as well as selective NSAIDs (eg, celecoxib [Celebrex]).
Kidney disease — NSAIDs can worsen kidney function in people whose kidneys are not functioning normally. Most people with chronic kidney disease are advised to avoid all types of NSAIDs. (See "Patient information: Chronic kidney disease (Beyond the Basics)".)
Aspirin allergy — People who have had hives (urticaria) or other symptoms of an allergy to aspirin should generally avoid NSAIDs, unless they have specifically discussed their reaction with a healthcare provider. People with certain types of reactions to one NSAID may be able to take another type safely. It may be necessary to consult with an allergy specialist who has experience with allergic reactions to NSAIDS. (See "Patient information: Hives (urticaria) (Beyond the Basics)".)
Aspirin and other NSAIDs may also cause worsening of asthma and related symptoms in some people with these conditions. This is not a true allergy but can be a significant problem for some people, who may need to avoid these medications if this occurs.
Celecoxib may be a safe alternative to aspirin in such people, but should be used with caution under the supervision of a clinician.
Pregnancy and breastfeeding — NSAIDS are not generally recommended for pregnant women during the third trimester due to an increased risk of complications in the newborn. NSAIDs are safe for use during breastfeeding. (See "Patient information: Maternal health and nutrition during breastfeeding (Beyond the Basics)".)
NONSTEROIDAL ANTIINFLAMMATORY DRUG OVERDOSE
Accidentally or intentionally taking a larger than recommended dose of an NSAID does not usually cause serious complications. However, taking large doses of other pain medications may have more serious consequences. For example, overdose with salicylates (eg, aspirin) or acetaminophen (eg, Tylenol) can be harmful or even fatal.
People who accidentally or intentionally take an overdose of any medication should contact their healthcare provider or the Poison Control Hotline (in the United States, 1-800-222-1222). If the person is not breathing or is not conscious, emergency medical attention is needed; this is available in most areas of the United States by calling 911.
WHERE TO GET MORE INFORMATION
Your healthcare provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.
Patient level information — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
Patient information: Nonsteroidal antiinflammatory drugs (NSAIDs) (The Basics)
Patient information: Osteoarthritis (The Basics)
Patient information: Bursitis (The Basics)
Patient information: von Willebrand disease (The Basics)
Patient information: Ankylosing spondylitis (The Basics)
Patient information: Calcium pyrophosphate deposition disease (pseudogout) (The Basics)
Patient information: Biceps tendinopathy (The Basics)
Patient information: Elbow tendinopathy (tennis and golf elbow) (The Basics)
Patient information: Separated shoulder (The Basics)
Patient information: Giving your child over-the-counter medicines (The Basics)
Patient information: Hand pain (The Basics)
Patient information: Achilles tendinopathy (The Basics)
Patient information: Reactive arthritis (The Basics)
Patient information: Toxic hepatitis (The Basics)
Patient information: Clavicle fracture (The Basics)
Patient information: De Quervain tendinopathy (The Basics)
Patient information: Tenosynovitis (The Basics)
Patient information: Rib fractures in adults (The Basics)
Patient information: Shinbone fracture (The Basics)
Patient information: Vertebral compression fracture (The Basics)
Patient information: Nose fracture (The Basics)
Patient information: Juvenile rheumatoid arthritis (The Basics)
Patient information: Boxer’s fracture (The Basics)
Patient information: Meniscal tear (The Basics)
Patient information: Muscle strain (The Basics)
Patient information: Patellofemoral pain syndrome (The Basics)
Patient information: Metatarsalgia (The Basics)
Patient information: Toe fracture (The Basics)
Patient information: Pelvic fracture (The Basics)
Patient information: Neck fracture (The Basics)
Patient information: Hemophilia (The Basics)
Patient information: Groin strain (The Basics)
Patient information: Chondromalacia patella (The Basics)
Patient information: Erythema nodosum (The Basics)
Patient information: Opioid pain medicines (The Basics)
Patient information: Chronic hives (The Basics)
Patient information: Iliotibial band syndrome (The Basics)
Patient information: Psoriatic arthritis in adults (The Basics)
Patient information: Psoriatic arthritis in children (The Basics)
Patient information: Diffuse idiopathic skeletal hyperostosis (The Basics)
Patient information: Ehlers-Danlos syndrome (The Basics)
Patient information: Microscopic colitis (The Basics)
Patient information: Medicines to prevent and treat blood clots: Warfarin (Coumadin) (The Basics)
Patient information: Medicines to prevent and treat blood clots: Dabigatran, rivaroxaban, apixaban, and edoxaban (The Basics)
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
Patient information: Peptic ulcer disease (Beyond the Basics)
Patient information: Warfarin (Coumadin) (Beyond the Basics)
Patient information: Chronic kidney disease (Beyond the Basics)
Patient information: Hives (urticaria) (Beyond the Basics)
Patient information: Maternal health and nutrition during breastfeeding (Beyond the Basics)
Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
COX-2 inhibitors and gastroduodenal toxicity: Major clinical trials
COX-2 selective inhibitors: Adverse cardiovascular effects
Nonselective NSAIDs: Adverse cardiovascular effects
Nonselective NSAIDs: Overview of adverse effects
NSAIDs (including aspirin): Pathogenesis of gastroduodenal toxicity
NSAIDs (including aspirin): Primary prevention of gastroduodenal toxicity
NSAIDs (including aspirin): Role in prevention of colorectal cancer
NSAIDs (including aspirin): Secondary prevention of gastroduodenal toxicity
NSAIDs (including aspirin): Treatment of gastroduodenal toxicity
NSAIDs and acetaminophen: Effects on blood pressure and hypertension
NSAIDs: Acute kidney injury (acute renal failure)
NSAIDs: Adverse effects on the distal small bowel and colon
NSAIDs: Electrolyte complications
NSAIDs: Mechanism of action
NSAIDs: Therapeutic use and variability of response in adults
Overview of selective COX-2 inhibitors
The following organizations also provide reliable health information.
●National Library of Medicine
●American Academy of Orthopaedic Surgeons
●United States Food and Drug Administration
- Lin J, Zhang W, Jones A, Doherty M. Efficacy of topical non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis: meta-analysis of randomised controlled trials. BMJ 2004; 329:324.
- Simon LS, Grierson LM, Naseer Z, et al. Efficacy and safety of topical diclofenac containing dimethyl sulfoxide (DMSO) compared with those of topical placebo, DMSO vehicle and oral diclofenac for knee osteoarthritis. Pain 2009; 143:238.
- Brooks PM, Day RO. Nonsteroidal antiinflammatory drugs--differences and similarities. N Engl J Med 1991; 324:1716.
- Walker JS, Sheather-Reid RB, Carmody JJ, et al. Nonsteroidal antiinflammatory drugs in rheumatoid arthritis and osteoarthritis: support for the concept of "responders" and "nonresponders". Arthritis Rheum 1997; 40:1944.
- Ray WA, Stein CM, Daugherty JR, et al. COX-2 selective non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease. Lancet 2002; 360:1071.
- Solomon DH, Schneeweiss S, Glynn RJ, et al. Relationship between selective cyclooxygenase-2 inhibitors and acute myocardial infarction in older adults. Circulation 2004; 109:2068.
All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.
- NONSTEROIDAL ANTIINFLAMMATORY DRUG OVERVIEW
- CHOOSING A NONSTEROIDAL ANTIINFLAMMATORY DRUG
- TOPICAL NONSTEROIDAL ANTIINFLAMMATORY DRUGS
- HOW NONSTEROIDAL ANTIINFLAMMATORY DRUGS WORK
- TYPES OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS
- NONSTEROIDAL ANTIINFLAMMATORY DRUG SIDE EFFECTS
- MEDICAL CONDITIONS AND NONSTEROIDAL ANTIINFLAMMATORY DRUGS
- NONSTEROIDAL ANTIINFLAMMATORY DRUG OVERDOSE
- WHERE TO GET MORE INFORMATION