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HEALTH GUIDE / Prescription Drugs / COX-2 inhibitors

COX-2 inhibitors

Cox II Inhibitors


About COX-2 inhibitors

Cyclo-oxygenase-2 (COX-2) inhibitors are special types of nonsteroidal anti-inflammatory drugs (NSAIDs). Like all NSAIDs, COX-2 inhibitors 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 both 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 the other NSAIDs, may offer a reduction in risk for colon cancer.

Currently, celecoxib (Celebrex) is the only type of COX-2 inhibitor approved for sale in the United States. It is approved by the U.S. Food and Drug Administration (FDA) for treatment of acute pain, stiffness or inflammation caused by arthritis. It may also at times be administered for off label uses (when a physician prescribes a medication for conditions other than those for which it was originally approved) such as menstrual pain.

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 (e.g., heart attack, stroke and serious skin reactions). Ongoing research is being conducted to determine if the benefits of these drugs outweigh the risks of side effects in certain situations (e.g., cancer treatment and prevention).

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 (e.g., heart attack, stroke, gastrointestinal bleeding).


Conditions of concern with COX-2 inhibitors

Celecoxib (Celebrex) is currently the only kind of cyclo-oxygenase 2 (COX-2) inhibitor approved for sale in the United States. Patients should not take this drug if they have been diagnosed with any of the following conditions:

  • Allergies to sulfonamide antibiotics or other sulfa drugs
  • Asthma
  • Hives
  • Allergic reactions to other nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin
  • Cardiovascular disease (or recent coronary artery bypass surgery)
  • Alcoholism
  • Bleeding problems, stomach ulcer or other intestinal problems
  • Tobacco use
  • Anemia (too few red blood cells in the blood)
  • Dehydration or abnormal fluid retention
  • Heart disease
  • High blood pressure
  • Kidney or liver disease
Side effects

Potential side effects of COX-2 inhibitors

The only type of cyclo-oxygenase 2 (COX-2) inhibitor currently approved for sale in the United States is celecoxib (Celebrex). Despite the potential benefits of using this drug for certain conditions (e.g., arthritis), serious side effects may occur. Sometimes side effects can happen without any warning, although warning symptoms often occur. Patients should notify their physician if they experience any of the following:

  • Swelling of the face, fingers, feet and/or lower legs
  • Intense abdominal pain or nausea
  • Black stools
  • Vomiting of blood or substance similar in appearance to coffee grounds
  • Unusual weight gain
  • Rash
  • Fever
  • Mouth sores
  • Drowsiness or fatigue
  • Itchiness

Because celecoxib has only been available for a short time, long term side effects have only recently begun to be documented and understood. A physician can asses a patient’s individual risk for certain complications.

In 2004, the COX-2 inhibitor rofecoxib (Vioxx) was voluntarily withdrawn from the market by its manufacturer after studies linked the drug to high blood pressure and increased risk of heart attack and stroke. The U.S. Food and Drug Administration (FDA) found that people who regularly took standard doses of the drug had a 50 percent higher chance of heart attack or sudden cardiac death than patients taking celecoxib.

Another COX-2 inhibitor, valdecoxib (Bextra), was voluntarily withdrawn for sale in the United States by its manufacturer in April 2005 because of evidence that the drug may be associated with an increased risk for heart attack, stroke and serious skin reactions (e.g., dermatitis). Research is investigating whether the benefits of the drug outweigh these potential risks in some instances (e.g., cancer treatment and prevention).

Other COX-2 inhibitors and some traditional nonsteroidal anti-inflammatory drugs (NSAIDs) may also pose similar risks for serious skin reactions. However, the risk of valdecoxib causing these effects appears to be much greater in comparison to the traditional drugs.

Research has also linked the use of celecoxib and other COX-2 inhibitors to serious side effects, including:

  • Stomach ache, diarrhea and headache. These are the most common side effects reported by people who take COX-2 inhibitors.
  • Stomach bleeding. COX-2 inhibitors can cause stomach bleeding in rare cases. The risk increases if alcohol is consumed daily or in excess.
  • Kidney or liver problems. Patients taking COX-2 inhibitors rarely experience problems with the kidney or liver. Blood may be monitored routinely by a physician to check for signs of kidney or liver damage in patients who commonly use these drugs.
  • Aseptic meningitis. In rare instances, rofecoxib can cause this non-bacterial form of meningitis. Aseptic meningitis requires hospitalization, but is typically not life threatening in individuals with normal immune systems. Individuals with autoimmune diseases (e.g., lupus) have a higher risk of contracting aseptic meningitis when taking rofecoxib.
  • Anaphylaxis. This is a rare but very serious allergic reaction that may occur in people allergic to aspirin, NSAIDs or certain antibiotics (e.g., sulfonamides).
  • Gastrointestinal bleeding. Bleeding of the intestines is a rare, but potentially serious side effect of COX-2 inhibitors.
  • Obstruction. In rare cases, blockage of the intestines may occur.
  • Perforation. A hole in the wall of an intestine may develop in rare cases.

Drug interactions

The only type of cyclo-oxygenase 2 (COX-2) inhibitor currently approved for sale in the United States is celecoxib (Celebrex). Patients should consult their physician before taking any additional prescriptions, over-the-counter medications, nutritional supplements or herbal medications. Concerns of individuals taking celecoxib include:

  • Nonsteroidal anti-inflammatory drugs (NSAIDs). May be administered in low doses. However, some NSAIDs (e.g., aspirin, ibuprofen) taken together with celecoxib may increase the risk for serious side effects (e.g., ulcer).
  • Fluconazole. An antifungal used to treat yeast infections. Use of this drug may increase the risk of side effects.
  • Lithium. Used to treat severe depression or bipolar disorder. High levels of celecoxib (Celebrex) in the blood, along with regular lithium use can increase the chance of side effects.
  • ACE inhibitors. A group of drugs that treat high blood pressure. Celecoxib and other Cox-2 inhibitors may diminish the effectiveness of ACE inhibitors.

Symptoms of COX-2 inhibitor overdose

Celecoxib (Celebrex) is the only cyclo-oxygenase 2 (COX-2) inhibitor currently approved for sale in the United States. Symptoms of celecoxib overdoses often resemble those associated with side effects, and may include:

  • Bloody or black stools
  • Prolonged thirst
  • Drowsiness
  • Headache
  • Nausea or vomiting of blood or material similar to coffee grounds
  • Abdominal pain
  • Shortness of breath
  • Swelling in the face, fingers and/or lower legs
  • Chest pain or wheezing
  • Unusual fatigue
How to use

Pregnancy use issues

How cyclo-oxygenase 2 (COX-2) inhibitors affect pregnant women, fetuses and newborns is not completely known. However, heart and blood flow problems in a fetus or newborn may occur if the mother regularly takes COX-2 inhibitors during the third trimester of pregnancy. Experiments on animals with these drugs have produced birth defects in some cases. Women are encouraged to advise their physician if they are pregnant or may become pregnant before taking COX-2 inhibitors.

Child use issues

Currently, COX-2 inhibitors have not been approved for use in children. Research has concentrated on adult patients. Relative comparisons to the effects on children are presently unavailable.

Elderly use issues

People age 65 and older have been tested in limited numbers to determine the effects of COX-2 inhibitors on this population. Results suggest that older individuals do not have a higher risk of experiencing side effects. However, in cases where side effects are experienced, they tend to be more serious than in younger adults.

Questions for your doctor

Patients may wish to ask their doctor the following questions about cyclo-oxygenase 2 (COX-2) inhibitors:
  1. Can a COX-2 inhibitor relieve my condition?
  2. What are the possible side effects?
  3. How likely am I to develop serious side effects from the use of COX-2 inhibitors?
  4. What alternative drugs can I use for my condition besides COX-2 inhibitors?
  5. Are there any new COX-2 inhibitors coming on the market that may work better for me?
  6. How long should I wait before consuming alcohol after taking COX-2 inhibitors?
  7. Should I stop using COX-2 inhibitors if I think I’m pregnant?
  8. I am allergic to sulfa drugs. Can I take COX-2 inhibitors?
  9. Are COX-2 inhibitors usually taken long-term?
  10. How long do I need to take COX-2 inhibitors before I see improvements?

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