The frequent use of nonsteroidal anti-inflammatory drugs (NSAIDs), a class of pain relievers, is second only to infection by the bacterium Helicobacter pylori (H. pylori) as a cause of peptic ulcers. Further, complications are more common with NSAID-induced peptic ulcers than those that result from other causes. The U.S. Food and Drug Administration (FDA) requires that the labels and package inserts of both prescription and over-the-counter NSAIDs contain warnings about these and other gastrointestinal (GI) risks.

NSAIDs are used to treat pain and inflammation in the body. They work by suppressing enzymes that produce prostaglandins, chemicals produced in response to pain that also protect the stomach lining. NSAIDs therefore have the combined effect of reducing pain while making the stomach lining more susceptible to damage. People who take NSAIDs regularly to alleviate chronic pain are more likely to develop problems such as peptic ulcers as the medication harms the stomach lining. However, damage may also occur in patients who only take NSAIDs occasionally or only take small doses.

Newer NSAIDs called COX-2 inhibitors affect only the inflammation-producing prostaglandins and are less damaging to the stomach lining. However, COX-2 inhibitors have been linked to an increased risk of serious cardiovascular problems (e.g., heart attack, stroke) and severe skin reactions. Because of this, several COX-2 inhibitors have been withdrawn from the U.S. market.

Not everyone has the same risk of GI side effects with NSAIDs. Most patients can take occasional NSAIDs without increasing their risk of peptic ulcers.

Patients who take prescription or over-the-counter NSAIDs should talk with a physician about the risk of ulcers and other GI side effects. Reduced dosages and alternative or additional medications may lessen these risks. The benefits of these medications must be weighed against their risks.

When ulcers occur, it is generally recommended that patients stop using any NSAIDs. Various other pain relievers (e.g., acetaminophen) may be used as alternatives to NSAIDs. However, it is not always possible to stop taking NSAIDs. These medications can be an important part of therapy for many inflammatory pain conditions (e.g., arthritis).

When the risk of adverse effects is high and NSAIDs are still required, reducing the dosage or changing or adding medications may help prevent peptic ulcers. Not all NSAIDs have the same degree of GI risk. In certain high-risk cases, medications frequently used to treat ulcers (e.g., proton pump inhibitors, H2 blockers) may be prescribed with NSAIDs to reduce the chance of developing the ulcers. The medication misoprostol (a synthetic version of a substance in the body that protects the stomach lining), has also been used successfully to prevent peptic ulcers in patients taking NSAIDs.

Because of the side effects caused by NSAIDs and their many interactions with other drugs and substances, patients are encouraged to consult their physician before using these drugs. Patients who take NSAIDS and experience the symptoms of a peptic ulcer should seek medical attention.

The regular use of pain relievers called nonsteroidal anti-inflammatory drugs (NSAIDs) is the second most common cause of peptic ulcers – sores that form in the stomach and surrounding portions of the gastrointestinal tract. The U.S. Food and Drug Administration (FDA) requires that the labels and package inserts of both prescription and over-the-counter NSAIDs contain warnings about gastrointestinal (GI) risks. Patients who frequently take NSAIDs and experience the symptoms of a peptic ulcer should seek medical attention.

NSAIDs are commonly used to reduce swelling and inflammation and to relieve pain and fever. They are a popular class of medications for patients with arthritis. These patients and others with chronic pain conditions use the drugs regularly and for lengthy periods of time. They may also be used for occasional pain relief. Although the risk of developing ulcers is greater with prolonged use or high doses of NSAIDs, even periodic, low-dose use carries some risk.

NSAIDs prevent pain by inhibiting the production of chemicals called prostaglandins. In addition to their role in pain and inflammation, prostaglandins help protect the delicate GI lining. In the stomach, this lining must be protected from the gastric juices that digest food. A complex, multilayered barrier protects the stomach lining with the following components:

• Mucus. Coats the stomach and duodenal lining and shields it from stomach acid.
  
  
• Bicarbonate. A chemical that neutralizes stomach acid.
  
  
• Circulation of blood to the lining of the stomach and duodenum. Aids in cell renewal and repair.

Prostaglandins stimulate the mucus, increase the bicarbonate production and also stimulate blood flow. All of these actions by prostaglandins keep the protective barrier intact. Since NSAIDs inhibit the production of prostaglandins, all of these mechanisms are hindered, weakening the barrier and allowing the digestive juices to damage the lining. This may result in ulcers.

Peptic ulcers are sores that form in the gastrointestinal lining due to injury by digestive juices. Peptic ulcers often cause burning pain in the upper abdomen. Other possible symptoms of peptic ulcers include nausea and vomiting, loss of appetite, unexplained weight loss and fatigue. It is important for people taking NSAIDs to recognize these symptoms and to report them to a physician.

Most peptic ulcers are caused by the bacterium Helicobacter pylori (H. pylori). Nearly all those not caused by H. pylori result from the use of NSAIDs. NSAIDs tend to cause peptic ulcers in the stomach (gastric ulcers) rather than the duodenum (duodenal ulcers). The opposite is true for H. pylori.

Peptic ulcers caused by NSAIDs usually heal after the medications are stopped. Any method of healing ulcers (e.g., H2 blockers, proton pump inhibitors) may be recommended to promote healing by diminishing acid. If H. pylori is present along with NSAID-induced ulcers, antibiotics will generally be used to treat the bacteria.

Surgery may be necessary if the ulcer does not heal, recurs after healing, or if complications (e.g., severe bleeding, perforation, obstruction) arise. Peptic ulcer complications are more common with NSAID-induced peptic ulcers than those that result from other causes.

According to the American College of Gastroenterology, the overall risk of serious GI problems in patients taking NSAIDs is about three times greater than in patients who do not take NSAIDs. These serious problems include peptic ulcer complications. Such serious, potentially life-threatening complications may even occur with no warning symptoms, especially in NSAID-induced ulcers. This may be at least partially due to the pain-reducing effects of NSAIDs.

NSAID-related damage can occur to the GI lining throughout the digestive tract, but occurs most often in the stomach and duodenum. Such damage generally results from frequent use of NSAIDs or high dosages of the medications. However, it may also occur in patients who only take NSAIDs occasionally or only take small doses of the drug.

When ulcers occur, it is generally recommended that patients stop using any NSAIDs. Alternative pain relievers, such as acetaminophen, may be used instead. Acetaminophen reduces pain and fever but does not reduce inflammation. Although it does not cause GI side effects, it does have its own set of risks. Patients are encouraged to discuss this and other alternatives to NSAIDs with their physicians.

Not all types of NSAIDs inhibit production of prostaglandins in the stomach lining. Newer versions, called COX-2 inhibitors, reduce pain with less likelihood of damage to the GI lining. However, COX-2 inhibitors have other drawbacks, such as an increased risk of heart attack and stroke (see Types and differences).

About 20 types of nonsteroidal anti-inflammatory drugs (NSAIDs) have been approved by the U.S. Food and Drug Administration (FDA). Each type of NSAID affects the body differently, with individuals responding better to some types than others. Physicians often switch between 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.

NSAIDs are available both with and without a prescription. Over-the-counter NSAIDs available in the United States include:

Other NSAIDs approved for sale in the United States include:

Most NSAIDs are traditional NSAIDs, which work by suppressing both forms of the enzyme cyclooxygenase (COX). COX-2 inhibitors are a newer type of NSAID that suppress only the COX-2 enzyme, not COX-1 (which is responsible for the prostaglandins in the stomach lining). COX-2 inhibitors are therefore effective in relieving pain with less risk of peptic ulcers. However, they still pose risks. COX-2 inhibitors have been linked to an increased risk of serious cardiovascular problems (e.g., heart attack, stroke) and severe skin reactions (e.g., Stevens Johnson syndrome). Because of this, several COX-2 inhibitors have been withdrawn from the U.S. market. Celecoxib (Celebrex) is the only COX-2 inhibitor currently available in the United States. The FDA is encouraging physicians who prescribe celecoxib to do so at the lowest effective dose and for the shortest possible duration.

Nonsteroidal anti-inflammatory drugs (NSAIDs) may also cause many non-ulcer side effects. Other gastrointestinal side effects - usually gastrointestinal bleeding - are among the most common of these. NSAIDs are a leading cause of hospitalizations related to adverse drug reactions.

Most NSAIDs have the potential to cause increased risks of cardiovascular problems (e.g., heart attack, stroke) and rare, but serious, skin reactions. However, aspirin has been shown to reduce the risk of heart attack and stroke in some patients. The degree of these risks may vary among individuals, but generally increases with the dosage and frequency of NSAID usage. The U.S. Food and Drug Administration (FDA) has called for label changes on many NSAIDs to include information about these potential risks. However, when used properly over brief periods of time, NSAIDs rarely produce serious side effects.

Common side effects of NSAIDs include:

• Indigestion or nausea
  
• Abdominal pain
  
• Diarrhea and bloating
  
• Heartburn
  
• Unusual bleeding (e.g., nosebleeds, irregular/heavy menstruation)
  
• Drowsiness or dizziness
  
• Headache or back pain
  
• Ringing in the ears or reduced hearing
  
• Stuffy or runny nose
  
• Sleeplessness
  
• Skin rashes or mouth sores
  
• Sensitivity to sunlight
  
• Fluid retention, leading to swollen feet, ankles, legs or hands
  
• Painful urination
  
• Unexplained weight gain

Other more severe side effects of NSAIDs include:

• Allergic reaction (sneezing, respiratory congestion, itching or skin rashes)
  
• High blood pressure
  
• Migraines
  
• Kidney or liver problems
  
• Chest tightness

Some side effects occur when patients first begin taking NSAIDs and then diminish after patients have 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 safely passed through the stomach. Lowering the dosage can also be effective.

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.  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. There is an increased chance of gastrointestinal bleeding if NSAIDs are combined with aspirin.
  
  
• Corticosteroids. NSAIDs taken in conjunction with corticosteroids (which are another type of anti-inflammatory drug) may increase the risk of peptic ulcers.
  
  
• Triamterene. This diuretic increases the chance of kidney problems when taken with NSAIDs.
  
  
• Antiemetics (medications that prevent or stop vomiting). Used in conjunction with NSAIDs, antiemetics may not be as effective.
  
  
• Blood pressure medications. Taking NSAIDs may reduce the effectiveness of these drugs.
  
  
• Chemotherapy drugs. Taking NSAIDs may increase the toxicity of some cancer fighting drugs.
  
  
• Arthritis, gout or diabetes medications. These drugs can interact 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.
  
  
• Cigarettes and alcohol. Smokers have an increased risk of developing gastric ulcers from NSAID use. Nausea and bleeding are common when NSAIDs are taken with alcohol.
  
  
• Vitamin E supplements and omega-3 fatty acid supplements. Each of these increases the likelihood of bleeding when taken along with NSAIDs.
  
  
• 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. People with insomnia may sleep more easily when an NSAID (e.g., aspirin, ibuprofen) is taken before bed. NSAIDs should never be taken with other pain relievers or anti-inflammatory medications unless under the direction of a physician.

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

New guidelines for health care providers require a thorough patient risk assessment that includes a careful examination of the patient’s medical history before prescribing NSAIDs. Whenever possible, physicians are to prescribe lower dosages of NSAIDs, limit the duration of NSAID use, treat any existing H. pylori infection prior to prescribing NSAIDs and institute any other necessary protective measures, such as prescribing alternative or additional medications.

Patients taking prescription or over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) should talk to a physician about the risk of peptic ulcers and other gastrointestinal (GI) side effects. Reduced dosages and alternative or additional medications may reduce these risks. The benefits of these medications must be weighed against their risks.

Various other pain relievers may be used as alternatives to NSAIDs. Among the most popular of these is acetaminophen. This medication reduces pain and fever but does not reduce inflammation. However, is also does not cause GI side effects. Acetaminophen is considered safe, but, like other drugs, it may cause problems when taken in high doses. It is included in many pain and cold medications. Patients with chronic liver disease are more prone to acetaminophen liver toxicity. Many patients take more acetaminophen than they realize. Because of this, it is important to inform physicians of all medications taken, including over-the-counter medications.

It is not always possible to stop taking NSAIDs. These medications can be an important part of therapy for many chronic pain conditions (e.g., arthritis), to the point that eliminating them is not a viable option. Further, aspirin has been shown to help prevent heart attack and perhaps stroke. These benefits can be obtained with a small daily dose. Such a dose poses a significantly reduced risk for GI problems. In patients at high risk of heart attack and stroke, aspirin’s benefits may outweigh the potential GI risks.

The risk of GI side effects with NSAIDs varies. Most patients can take occasional NSAIDs without increasing their risk of peptic ulcers. In general, most patients at low risk are usually not advised to take additional medications to reduce the GI risks. In some cases, there are enough risk factors that warrant continued monitoring and active preventative measures. These risks include:

• Age. Patients over 60 years of age have a much greater risk of developing peptic ulcers.
  
  
• Previous ulcer. Patients with a history of ulcer disease have an increased chance of developing subsequent ulcers.
  
  
• Dosage. Patients who take higher dosages of NSAIDs have a greater risk of developing peptic ulcers.
  
  
• Cigarettes and alcohol. Alone, both can cause GI irritation. NSAID use added to this irritation may result in elevated GI risks.
  
  
• Steroids. The combined use of NSAIDs and corticosteroids greatly increases the risk of gastrointestinal bleeding, according to the American College of Gastroenterology (ACG).
  
  
• Anticoagulants. According to the ACG, combined use of NSAIDs and oral prescription anticoagulants substantially increase the risk of GI bleeding.

When the risk of adverse effects is high and NSAIDs are still required, reducing the dosage or changing or adding medications may help prevent peptic ulcers. Not all NSAIDs have the same degree of GI risk. COX-2 inhibitors (e.g., celecoxib) have a lower risk of peptic ulcers and other GI problems (although they carry other risks - see Types and differences) than traditional NSAIDs. Other low-risk NSAIDs include ibuprofen and diclofenac. Medium risk NSAIDs include naproxen, indomethacin and piroxicam. High-risk NSAIDs include ketoprofen.

In certain high-risk cases, medications used to treat ulcers may be prescribed with NSAIDs to reduce the chance of developing the ulcers. Proton pump inhibitors may be the more useful of these. H2 blockers can prevent duodenal ulcers, but not gastric ulcers. The medication misoprostol may also be an option. This is a synthetic prostaglandin that replaces the prostaglandin responsible for protecting the stomach. Misoprostol has been successfully used to prevent peptic ulcers in patients taking NSAIDs, but is more expensive than proton pump inhibitors.

Research also indicates that the acid-reducing drug esomeprazole magnesium may reduce ulcer risk in NSAID users with an increased risk of developing ulcers.

Symptoms of overdose can be similar to the side effects of nonsteroidal anti-inflammatory drugs (NSAIDs), but are usually more severe. Patients exhibiting any of these symptoms should contact their physician immediately:

• Bluish lips, skin or fingernails
• Severe and lingering headache
• Nausea or vomiting
• Difficulty breathing
• Fast or pounding heartbeat
• Confusion, agitation or incoherence
• Blurred vision
• Skin rash
• Abdominal pain or diarrhea
• Convulsions or seizures
• Hemorrhage (heavy bleeding) from stomach or intestine

In rare cases, the patient may also go into a coma (prolonged unconsciousness).

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.

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’s syndrome (a disease that affects all organs and can cause swelling of the brain and liver) in children. The use of aspirin during flu and 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 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 such as peptic ulcers. According to the American College of Gastroenterology (ACG), the overall risk of serious gastrointestinal (GI) problems in patients over the age of 60 who take NSAIDs is five times greater than those who do not take these medications. By contrast, the ACG reports that the risk is only slightly more than 1.5 times greater in younger patients. Further, the relative risk of GI surgery is 10 times greater in elderly patients taking NSAIDs, according to the ACG, and the risk for GI-related cause of death is 5.5 times greater.

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

Preparing questions in advance can help patients to have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions about nonsteroidal anti-inflammatory drugs (NSAIDs) and peptic ulcer:

1. What is my risk of NSAID-induced peptic ulcers?
   
   
2. Would changing to another type of NSAID reduce my risk?
   
   
3. Are COX-2 inhibitors an option for me? What are the risks of these medications?
   
   
4. Would it help me to take some other medication, such as a proton pump inhibitor, along with my NSAIDs?
   
   
5. Do the benefits of NSAIDs outweigh the risks for me?
   
   
6. Would reducing the dosage of my NSAIDs help my ulcer while still treating my symptoms?
   
   
7. What non-NSAID medications would be good alternatives for the relief of my symptoms?
   
   
8. Might I also be infected with Helicobacter pylori?
   
   
9. If my ulcer does not heal after I stop taking NSAIDs, what treatment options would be best for me?
   
   
10. After this ulcer is treated, will my risk of NSAID-induced peptic ulcers be high enough to prohibit my future use of NSAIDs?