Selective cyclo–oxygenase–2 (COX–2) inhibitors are special types of nonsteroidal anti–inflammatory drugs (NSAIDs). Like all NSAIDs, selective COX–2 inhibitors, also called coxibs, work by blocking the production of prostaglandins, hormone–like substances in the body that are quickly released at the site of an injury or area of pain. The presence of these chemicals registers in the brain as pain. Prostaglandins protect damaged tissues by bathing them in fluids, causing the tissue to swell or inflame. By blocking the production of prostaglandins, NSAIDs reduce the amount of fluid released after an injury and the level of pain experienced.

COX–2 inhibitors differ from traditional NSAIDs by targeting only the pain–signaling prostaglandins. They do not affect cyclo–oxygenase 1 (COX–1), a chemical associated with protecting the stomach lining. Consequently, COX–2 inhibitors may be able to relieve pain without causing stomach problems (e.g., ulcers) often associated with other NSAIDs. Evidence also suggests that some COX–2 inhibitors, like other NSAIDs, may reduce the risk of colon cancer.  

Currently, celecoxib (Celebrex) is the only type of COX–2 inhibitor approved for sale in the United States. According to the U.S. Food and Drug Administration (FDA), it is used for:

• Relieving symptoms of osteoarthritis, rheumatoid arthritis and juvenile rheumatoid arthritis

• Controlling acute pain in adults, such as surgical or dental pain
  
  
• Easing menstrual pain
  
  
• Reducing colorectal polyps in people who have an inherited condition called familial adenomatous polyposis (FAP) that increases the risk of colorectal cancer

In addition, recent research suggests that short-term use of COX-2 inhibitors may be safe to reduce the abdominal pain of  inflammatory bowel disease.

The other two COX–2 inhibitors previously available, valdecoxib (Bextra) and rofecoxib (Vioxx), were each removed from the market by their respective manufacturers. Studies associated these drugs with a greater risk for developing certain serious health problems such as heart attack, stroke and serious skin reactions. Research is being conducted to determine if the benefits of these drugs outweigh the risks of side effects in certain situations, such as treating and preventing cancer. Recent research has suggested that rofecoxib may relieve acute attacks of migraines.

The FDA determined that the benefits of celecoxib outweighed the risks for some patients. It remains on the market with additional warnings on the label about serious risks in patients with certain conditions including heart attack, stroke and gastrointestinal bleeding.

Recent research has produced mixed results on the cardiovascular safety of COX-2 inhibitors compared to some other NSAIDs. For example, a study of more than 650,000 arthritic adults found the probability of heart attack rose 9 percent in those treated with celecoxib, 32 percent in those treated with rofecoxib, 11 percent with ibuprofen, 41 percent with sulindac and 71 percent with indomethacin. As dosages increased, so did the risk. Another study found, in people who have had a heart attack, high-dose diclofenac to be less risky than high-dose COX-2 inhibitors but riskier than low-dose COX-2 inhibitors. Another study found a potential new COX-2 inhibitor, etoricoxib (Arcoxia), had cardiovascular risks comparable to those of diclofenac.

Individuals’ response to COX-2 inhibitors may vary in part because of genetics. Further study to identify who is likely to benefit and who is likely to experience side effects from a medication could increase the safety of COX-2 inhibitors and other drugs.

Recent research indicates that taking COX-2 inhibitors or some other NSAIDs around the time of a vaccination may hinder the vaccine’s effectiveness. Patients scheduled for a flu shot or other vaccination are advised to ask their physician whether they should restrict use of such medications around that time.