What is Celebrex?

Celebrex is used to:

• relieve symptoms of osteoarthritis (the arthritis caused by age-related “wear and tear” on bones and joints)
• relieve symptoms of rheumatoid arthritis in adults
• manage acute pain in adults (like the short term pain you can get after a dental or surgical operation)
• treat painful menstrual cycles
• reduce the number of colon and rectum growths (colorectal polyps) in patients with a disease called Familial Adenomatous Polyposis (FAP). FAP is an inherited disease in which the rectum and colon are covered with many polyps. Celebrex is used along with the usual care for FAP patients such as surgery and exams of the rectum and colon.

Who Should Not Take Celebrex?

Do not take Celebrex if you:

• have had an allergic-type reaction to sulfa medicines.
• have had asthma, hives or allergic-type reactions after taking aspirin or other NSAID (nonsteroidal anti-inflammatory drugs) medicines. If you have asthma, you may have aspirin-sensitive asthma. If an aspirin-sensitive asthmatic takes aspirin it can cause severe narrowing of the airway (bronchospasm), and even death. Since this type of reaction also has occurred after taking NSAIDs Celebrex should not be given to aspirin-sensitive patients.

Some examples of NSAIDs are ibuprofen (Motrin, Advil), naproxen (Naprosyn, Aleve), diclofenac (Voltaren, Cataflam), and ketoprofen (Orudis). You can ask your doctor or pharmacist for a complete list of these medications.

• are pregnant, especially during your last 3 months

What are The Risks?

Celebrex and other NSAID medicines can cause serious problems such as:

• Stomach ulcers that bleed. The chance of this serious problem increases the longer you take Celebrex, but it can also happen suddenly. Stop taking Celebrex and call your healthcare professional right away if you get a burning stomach pain, black bowel movements that look like tar, or vomit that looks like blood or coffee grounds.
   
• Liver damage. Some of the warning signs of liver damage are nausea, vomiting, tiredness, loss of appetite, itching, yellow coloring of skin or eyes, “flu-like” symptoms and dark urine. If this happens, stop taking Celebrex and call your healthcare professional right away.
   
• Kidney problems that include sudden kidney failure or worsening of kidney problems that you already have.
   
• Fluid retention (holding of water in your body) and swelling. Fluid retention can be a serious problem if you have high blood pressure or heart failure.

In addition to the serious side effects listed above, some common, but less serious side effects with Celebrex may include:

• headache
• indigestion
• upper respiratory tract infection (a "cold")
• diarrhea
• sinus inflammation
• stomach pain
• nausea

What Should I Tell My Healthcare Professional?

Tell your healthcare professional if you:

• have heart problems or high blood pressure
• have liver or kidney problems
• have or had stomach ulcers or stomach bleeding
• have asthma
• are allergic to aspirin or other NSAID medicines
• are trying to become pregnant, are already pregnant, or are breast-feeding

Are There Any Interactions With Drugs or Foods?

Tell your healthcare professional about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Some medicines may affect how Celebrex works or Celebrex may affect how your other medicines work. Your healthcare professional may have to adjust your dose or watch you closely if you take any of the following medications:

• certain blood pressure medicines called ACE inhibitors
• furosemide
• fluconazole or ketoconazole
• phenytoin
• warfarin
• aspirin

Date created: April 7, 2005

Celebrex has been associated with an increased risk of serious adverse cardiovascular (CV) events in a long-term placebo controlled trial. Based on the currently available data, FDA has concluded that an increased risk of serious adverse CV events appears to be a class effect of non-steroidal anti-inflammatory drugs (NSAIDs) (excluding aspirin). FDA has requested that the package insert for all NSAIDs, including Celebrex, be revised to include a boxed warning to highlight the potential increased risk of CV events and the well described risk of serious, and potentially life-threatening, gastrointestinal bleeding. FDA has also requested that the package insert for all NSAIDs be revised to include a contraindication for use in patients immediately post-operative from coronary artery bypass (CABG) surgery.

Recommendations

• Physicians are encouraged to carefully weigh the potential benefits and risks of Celebrex and other treatment options for the condition to be treated before a decision is made to use Celebrex. If Celebrex is selected for an individual patient, FDA encourages use of the lowest effective dose for the shortest duration consistent with individual patient treatment goals.

• Celebrex should not be used in patients who are immediately post-operative from CABG surgery.

Data Summary

• In the National Cancer Institute’s Adenoma Prevention with Celecoxib (APC) trial in patients at risk for recurrent colon polyps, a 2-3 fold increased risk of serious adverse CV events was seen for Celebrex compared to placebo after a mean duration of treatment of 33 months. There appeared to be a dose response relationship, with a hazard ratio of 2.5 for Celebrex 200 mg twice daily and 3.4 Celebrex 400 mg twice daily for the composite endpoint of death from CV causes, myocardial infarction (MI), or stroke.
   

• In the nearly identical Prevention of Spontaneous Adenomatous Polyps (PreSAP) trial, the APC results were not replicated. Based on preliminary, unpublished data presented by the investigators at the February 16-18, 2005, FDA meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee, the hazard ratio was 1.1 for celecoxib 400 mg once daily compared to placebo for the composite endpoint of death from CV causes, MI, or stroke. (Extensive data related to the cardiovascular safety of Celebrex and other COX-2 selective and non-selective NSAIDs were presented at this Advisory Committee meeting. This information is available on the following website: http://www.fda.gov/ohrms/dockets/ac/cder05.html#ArthritisDrugs).
   

• Another long-term controlled trial, the National Institute of Aging’s Alzheimer’s Disease Anti-Inflammatory Prevent Trial (ADAPT), compared Celebrex 200 mg twice daily to placebo in patients at risk for Alzheimer’s disease. Data are not yet available from this trial; however, a preliminary report released by NIH on December 20, 2004, (http://www.nih.gov/news/pr/dec2004/od-20.htm) suggested that no increased risk of serious adverse CV events was found for Celebrex compared to placebo.
   

• The only available data from a long-term comparison of Celebrex to other NSAIDs come from the Celebrex Long-Term Arthritis Safety Study (CLASS) in which Celebrex 400 mg twice daily was compared to diclofenac and ibuprofen in approximately 8,000 patients with osteoarthritis. No differences were observed for serious adverse CV events between Celebrex and the two NSAID comparators in this trial.
   

• In two short-term placebo-controlled clinical trials in patients immediately post-operative from CABG surgery, valdecoxib, another COX-2 selective NSAID, was associated with an approximately two-fold increased risk of serious adverse CV events compared to placebo. No data are available for Celebrex in the post-CABG surgery population; however, pending receipt of further data, FDA has concluded that all NSAIDs, including Celebrex, should be contraindicated in patients immediate post-operative from CABG surgery.
   

Date created: April 7, 2005