Nonsteroidal anti-inflammatory drugs

Types and differences of NSAIDs

The U.S. Food and Drug Administration (FDA) has approved about two dozen types of nonsteroidal anti–inflammatory drugs (NSAIDs). Each type of NSAID affects the body differently, with individuals responding better to some types than others.

Physicians often switch among different NSAIDs for a patient to find the drug that is the most effective with the fewest side effects. The choice of one NSAID over another should be made after considering an individual’s risk factors for these potential side effects.

Among the NSAIDs are subgroups of medications, such as:

• Salicylates. Aspirin and related drugs, such as salsalate.
• COX-2 inhibitors. Drugs designed to relieve pain and inflammation without upsetting the stomach. Celecoxib remains the only COX-2 inhibitor sold in the United States after rofecoxib and valdecoxib were withdrawn because of side effects.

NSAIDs approved for sale in the United States include:

There are also many combination products that mix an NSAID with other ingredients, such as an anti-anxiety agent, an anticoagulant, a barbiturate, caffeine, a decongestant, an opioid or a sleep aid.

Conditions treated with NSAIDs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat a variety of conditions that involve pain and inflammation, including:

• Arthritis, including osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, gout (if recommended by a physician), pseudogout, psoriatic arthritis, Reiter’s syndrome and juvenile arthritis
• Muscle sprains and strains
• Minor injuries and trauma pain
• Illnesses that cause a fever
• Headaches, including tension headaches and migraines
• Some types of eye pain and ear pain
• Toothaches and other types of dental pain, orofacial pain and TMJ disorder
• Neck pain, including whiplash
• Back pain, including back sprain, degenerative disc disease, herniated disc, sciatica and spinal stenosis
• Chest pain, including costochondritis
• Shoulder pain
• Arm and wrist pain, including tennis elbow and carpal tunnel syndrome
• Menstrual cramps and other types of pelvic pain
• Sexual pain and testicular and scrotal pain
• Leg pain, knee pain and foot pain
• Joint pain from conditions such as Lyme disease and systemic lupus erythematosus
• Allodynia
• Cancer pain
• Chronic fatigue syndrome
• Complex regional pain syndrome
• Fibromyalgia
• Symptoms of meningitis and encephalitis
• Polymyalgia rheumatica
• Sarcoidosis
• Sickle cell anemia

Aspirin, a type of NSAID, may also be taken daily by some patients with cardiovascular disease to reduce the risk of heart attack. However, no other NSAID can be used for this purpose. Aspirin is beneficial to the cardiovascular system because it also has mild anti-platelet properties, which prevent the formation of blood clots. Interested patients are advised to consult their physician about the benefits and risks of aspirin therapy.

Regular use of aspirin or other NSAIDs reduces the risk of colorectal cancer and stomach cancer, according to authorities such as the American Cancer Society. The U.S. Food and Drug Administration (FDA) has approved use of the COX-2 inhibitor celecoxib to reduce the number of polyps in people with a hereditary condition called familial adenomatous polyposis that raises the risk of colorectal cancer.

Some studies suggest that NSAIDs might reduce the risk of other cancers, such as those of the esophagus, mouth, lungs, brain, skin, prostate, ovaries and breasts. The FDA has approved a diclofenac gel (Solaraze) to treat precancerous skin lesions called actinic keratoses.

People who regularly take NSAIDs might also have lower risk of some other conditions, including benign prostatic hyperplasia and asthma, according to recent research. However, because of the gastric and other side effects of these medications, physicians generally do not recommend taking NSAIDs merely for these potential benefits.

Regular use of ibuprofen may prevent or delay Parkinson’s disease, according to recent data from the Cancer Prevention Study II Nutritional Cohort, a study involving about 147,000 American adults. Yet ibuprofen is still not indicated for this purpose, as further research is needed. Other NSAIDs and acetaminophen had no such effect in the project.

Scientists are studying whether NSAIDs can help fight Alzheimer’s disease. A clinical trial sponsored by the U.S. National Institutes of Health found naproxen and the COX-2 inhibitor rofecoxib ineffective in slowing cognitive decline in patients with the disease, but the researchers stated that it was possible NSAIDs might have a role in preventing Alzheimer’s.

Conditions of concern

Patients may be advised by their physician not to take nonsteroidal anti-inflammatory drugs (NSAIDs) if they have any of the following conditions:

• Aspirin sensitivity. People who have an allergic reaction to aspirin often have sensitivity to other NSAIDs as well. An allergic reaction to NSAIDs can be serious and result in life-threatening anaphylactic shock. Individuals who have an allergic reaction to NSAIDs should seek immediate medical attention.
• Heart problems. COX-2 inhibitors, a subclass of NSAIDs, have been linked to increased stroke and heart attack risk. For this reason, two of these medications (rofecoxib and valdecoxib) have been withdrawn from the market. In addition, some NSAIDs may worsen heart failure, increase blood pressure, increase the risk of a second heart attack and reduce the effectiveness of some heart medications. People with heart problems should consult their physician about taking NSAIDs regularly. Some patients are advised by a cardiologist to take a small dose of aspirin daily to reduce their risk of heart attack or stroke.
• Stomach problems. NSAIDs can alter stomach chemistry and enzymes, causing irritation. Serious problems can develop (e.g., gastric ulcers, stomach bleeding) if this alteration is prolonged.
• Kidney or liver problems. NSAIDs are potentially damaging to these organs if taken in high doses or for extended periods of time. Conditions that may cause kidney damage include systemic lupus erythematosus, sickle cell anemia and diabetes.
• Hives (red, swollen patches of skin). Using NSAIDs can worsen this condition.
• Fluid retention (edema). Using NSAIDs may increase fluid retention, especially in the feet and ankles. Individuals with edema should avoid using NSAIDs.
• Inflammatory bowel disease (IBD). NSAIDs can trigger this condition. However, two recent studies suggest that patients may be able to take COX-2 inhibitors briefly without causing their IBD to flare up.
• Nasal polyps (round pieces of tissue that extend into the nasal cavity). The use of NSAIDs can complicate this condition in certain populations.
• Ulcers, sores or white spots in the mouth. Developing sores in the mouth while taking NSAIDs often indicates the medicine is causing serious side effects. If sores are present before the medication is started, it can be harder to detect serious side effects.
• Asthma. Recent research suggests that regular use of aspirin might reduce the risk of developing asthma. However, people who have asthma are generally advised to avoid NSAIDs because the drugs can trigger attacks. This occurs because the drugs interfere with the body’s production of the COX enzyme. Though the mechanism is unclear, it appears that the disruption of COX results in the constriction of the airways. Because of this sensitivity, physicians recommend that patients with asthma use acetaminophen in place of NSAIDs. However, patients sensitive to NSAIDs may also have reactions to acetaminophen and should discuss its use with their physician. People with asthma often also have problems with chronic sinusitis or nasal polyps. A physician may determine that an individual with asthma is able to tolerate COX-2 inhibitors.
• Gout or bleeding disorders. Patients with these conditions may be advised by their physician to avoid taking NSAIDs.
• Parkinson’s disease. NSAIDs should not be used in conjunction with several of the medications commonly prescribed to treat Parkinson’s disease, unless prescribed by a physician.
• Mental illness. Because NSAID use may cause some psychiatric medications to become toxic in the body, they should be used only with a physician’s prescription.

Patients should generally not take NSAIDs before undergoing surgery. These medications prevent blood clotting, which is necessary for healing wounds.

Potential side effects

When used properly over brief periods of time, nonsteroidal anti-inflammatory drugs (NSAIDs) rarely produce serious side effects. However, long-term usage or larger doses of NSAIDs increase the potential risk of side effects.

The U.S. Food and Drug Administration (FDA) estimates that 10,000-20,000 deaths occur each year as a result of NSAID-induced gastrointestinal disorders (usually bleeding). NSAIDs are the number one cause of drug-related hospitalizations.

Common side effects of NSAIDs include:

• Upset stomach or nausea
• Abdominal pain
• Diarrhea
• Bloating
• Heartburn
• Unusual bleeding (e.g., nosebleeds, irregular/heavy menstruation)
• Drowsiness
• Dizziness
• Ringing in the ears (tinnitus) or reduced hearing
• Stuffy or runny nose
• Sleeplessness
• Skin rashes
• Sensitivity to sunlight
• Fluid retention, leading to swollen feet, ankles, legs or hands
• Painful urination (dysuria)
• Unusual weight gain

More severe side effects of NSAIDs include:

• Allergic reactions (sneezing, respiratory congestion, itching or skin rashes)
• High blood pressure
• Stomach bleeding
• Migraines
• Stomach ulcers (with long-term use)
• Kidney or liver problems
• Chest tightness

Some side effects occur when the patient first begins taking NSAIDs and then diminish after the patient has been taking the medication for several days. In addition, the severity of some side effects can be reduced by taking the medication with food or by choosing enteric-coated medications that do not release the NSAID into the bloodstream until it has passed through the stomach. Lowering the dosage can also be effective. Patients may also lower the risk of gastrointestinal side effects by taking over-the-counter antacids.

Drug or other interactions

Patients should consult their physician before taking any additional prescriptions, over-the-counter medications, nutritional supplements or herbal medications. Of particular concern to individuals taking nonsteroidal anti-inflammatory drugs (NSAIDs) are:

• Aspirin. Aspirin increases the chance of developing serious side effects if taken regularly with other NSAIDs.
• Blood pressure medications. Taking NSAIDs may reduce the effectiveness of these drugs.
• Triamterene. This diuretic increases the chance of kidney problems when taken with NSAIDs.
• Cimetidine. This drug, used to treat gastrointestinal disorders, increases the chance of kidney problems when taken with NSAIDs.
• Chemotherapy drugs. Taking NSAIDs may increase the toxicity of some cancer-fighting drugs.
• Arthritis, gout or diabetes medication. These drugs can interact poorly with NSAIDs in some instances.
• Anticoagulants (medications that inhibit the blood’s ability to clot). Taking NSAIDs along with anticoagulants may increase the risk of excessive bleeding.
• Lithium carbonate. The effect and toxicity of this compound used to treat bipolar disorder may increase when taken along with NSAIDs.
• Immunosuppressants (medications that suppress the immune system). These may lessen the medicinal effects of NSAIDs.
• Corticosteroids (anti-inflammatory medications). NSAIDs taken in conjunction with corticosteroids may increase the risk of stomach ulcers.
• Anti-emetics (medications that prevent or stop vomiting). When used in conjunction with NSAIDs, anti-emetics may not be as effective.
• Cigarettes and alcohol. Smokers have an increased risk of developing stomach ulcers from NSAID use. When alcohol and NSAIDs interact, nausea and bleeding of the stomach may occur.
• Vitamin E supplements and omega-3 fatty acid supplements. Each of these increases the likelihood of bleeding when taken along with NSAIDs.
• Chondroitin. This supplement has a chemical composition similar to anticoagulants.
• Zinc. Reduces the absorption and effectiveness of NSAIDs.

In addition, NSAID use can decrease melatonin levels in the body.

Supplements that help build cartilage in joints (e.g., chondroitin, glucosamine) may enhance the anti-inflammatory properties of NSAIDs. Copper supplements may bind to NSAIDs and increase their anti-inflammatory properties as well. NSAIDs should never be taken with other pain relievers (analgesics) or anti-inflammatory medications unless under the direction of a physician.

There is conflicting evidence about the effect of other NSAIDs on aspirin. Some studies suggest that some types of NSAID may reduce aspirin’s effectiveness in patients having a heart attack. Other studies have suggested that regular – but not intermittent – use of NSAIDs may have an impact on the effects of aspirin. Additional studies have shown that an NSAID may not reduce an aspirin's effectiveness when the aspirin is taken two hours before the NSAID. It is recommended that if patient is taking ibuprofen for pain control and aspirin for anticoagulation, aspirin should be taken at least two hours before ibuprofen.

It is important for patients to tell their physician all the medications they are taking, whether prescribed or over the counter.

Pregnancy use issues

Pregnant women should avoid taking nonsteroidal anti-inflammatory drugs (NSAIDs) unless otherwise directed by a physician who is familiar with their condition. Though human studies evaluating birth defects caused by NSAIDs are unavailable, these drugs can potentially cause heart or blood flow problems in fetuses and newborns. Animal studies demonstrate a link between NSAID use and complications with pregnancy and delivery.

Many NSAIDs pass into the breast milk of breastfeeding mothers. Furthermore, several are believed to cause unwanted effects in nursing children. Nursing mothers should avoid taking NSAIDs and are encouraged to discuss possible drug alternatives with their physicians.

Child use issues

Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious side effects in adults. In children, the risks and intensity of side effects are even greater. Parents are encouraged to speak with their child’s physician about the risks and benefits of using NSAIDs. Some of the regularly used NSAIDs that may put children at an increased risk include:

• Aspirin. This NSAID has been linked to incidences of Reye syndrome (a disease that affects all organs and can cause swelling of the brain and liver) in children. The use of aspirin during bouts of the flu or viral illnesses (e.g., chickenpox) should be avoided for children.
• Phenylbutazone. Children under age 15 are advised not to take this NSAID.
• Naproxen. Children under age 2 have an increased risk of developing a skin rash when using this drug.
• Oxaprozin. There are no clinical studies of this drug type in children under 2 years of age. However, the drug has been safely used in older children who suffer from arthritis.
• Indomethacin and tolmetin. Neither of these NSAIDs has been tested in children younger than 2 years. Older children who have used these drugs have experienced the same side effects as adults.
• Ibuprofen. This NSAID has not been tested in children younger than 6 months. However, results from tests show that older children experience side effects similar to those commonly experienced by adults.

Elderly use issues

Elderly individuals are more sensitive to nonsteroidal anti–inflammatory drugs (NSAIDs) and have an increased risk of related side effects. Phenylbutazone may cause serious side effects in patients over 40 years of age, and the risk increases with age. Elderly individuals have the tendency to become very ill if the use of an NSAID results in stomach problems. Other NSAID side effects that often affect the elderly include:

• Confusion
• Swelling of the face, feet or lower legs
• Sudden decrease in the amount of urine
• Inability of the blood to clot
• Cardiac effects