Celecoxib

Celecoxib is a prescription non-steroidal anti-inflammatory drug (NSAID) in the cyclooxegenase-2 (COX-2) inhibitor family. It is most often used to treat the pain and inflammation caused by osteoarthritis and rheumatoid arthritis, and to reduce the number of colorectal polyps. Other drugs in the COX-2 inhibitor family include rofecoxib (Vioxx), valdecoxib (Bextra), lumiracoxib (Prexige) and etoricoxib (Arcoxia). These medicines have been shown to be very effective and lack many of the gastrointestinal side effects of other anti-inflammatory drugs but have been subject to a great deal of controversy relating to potentially fatal complications.

Source: Wikimedia Commons

Other Names

• Celebrex

Uses

Celecoxib 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 (recent onset, short course) pain in adults
• Treat painful menstrual cycles
• Reduce the number of colon and rectal 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. Celecoxib is used along with the usual care for FAP patients such as surgery and exams of the rectum and colon.

How Celecoxib Is Taken

Celecoxib is prescribed as 100 mg or 200 mg oral capsules. It can be taken either once a day or twice a day. The usual dose for osteoarthritis is 100 or 200 mg a day, and the dose for rheumatoid arthritis is 200 mg once or twice a day.

At doses up to 200 mg twice a day, celecoxib can be taken with or without food. Higher doses (400 mg twice a day) should be taken with food to improve absorption.

How It Works

Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) which is believed to work by inhibiting prostaglandin synthesis. Prostaglandins cause inflammation through two enzymes: cyclooxygenase-1 (COX-1), and cyclooxegenase-2 (COX-2). Celecoxib works by blocking the COX-2 enzyme without significant effect on the COX-1 enzyme. This selectivity decreases the gastrointestinal side effects of the drug.

How the body affects Celecoxib

Peak plasma levels occur approximately three hours after an oral dose of celecoxib. The drug is metabolized primarily in the liver, with excretion of the metabolites occurring through the stool and urine (57% and 27%, respectively). ^[1]

Benefits

Traditional NSAIDs work by blocking both COX-1 and COX-2. As mentioned above, COX-2 inhibitors work by blocking the COX-2 enzyme only. By blocking the COX-2 enzyme, celecoxib can help block pain and inflammation and still allow the COX-1 enzyme to work. The COX-1 enzyme is needed to help protect the stomach lining and decrease the chance of stomach ulcer and/or bleeding. Therefore, COX-2 inhibitors can help relieve pain and inflammation while protecting the stomach.

Side Effects

In addition to the serious possible complications listed in the section entitled "Risks" below, some common, but less serious side effects with celecoxib may include:

• Headache
• Indigestion
• Upper respiratory tract infection (a "cold")
• Diarrhea
• Sinus inflammation
• Stomach pain
• Nausea

Risks

Complications

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

• Bleeding ulcers: The chance of this serious problem increases with longer use of the medication. Signs of an ulcer may include 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.
• Kidney problems: Examples include sudden kidney failure or worsening of pre-existing kidney problems.  
• Fluid retention and swelling: Fluid retention can be a serious problem if it occurs in a person with high blood pressure or heart failure.
• Heart attack and stroke: As seen in the black box warning, COX-2 inhibitors have been linked with an increase in heart attack and stroke. Recent heart bypass surgery is a contraindication to the use of celecoxib.

Interactions

Some medicines may interact with celecoxib, or cause dangerous side effects when taken in conjunction with celecoxib. These medicines include:

• Certain blood pressure medicines called ACE inhibitors
• Furosemide
• Fluconazole or ketoconazole
• Lithium
• Phenytoin
• Warfarin
• Aspirin
• NSAIDs

Other medicines may require a dose adjustment, and patients on these medications may need to be monitored more frequently.

Precautions

Individuals should not take celecoxib if they have:

• Heart problems or high blood pressure
• Liver or kidney problems
• A history of stomach ulcers or stomach bleeding
• Asthma
• An allergy to aspirin or other NSAID medicines
• Planning on becoming pregnant, or are already pregnant
• An allergic-type reaction to sulfa medicines
• Asthma, hives or allergic-type reactions after taking aspirin or other NSAID (nonsteroidal anti-inflammatory drugs) medicines. Some asthma is 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, celecoxib should not be given to aspirin-sensitive patients.

Celecoxib has been linked to an increased risk of serious cardiovascular (CV) events (such as heart attack or stroke) which appears to be a risk shared by all medicines called non-steroidal anti-inflammatory drugs (NSAIDs) (excluding aspirin). The FDA has requested that the package insert (labeling) for all NSAIDs, including celecoxib, be revised to include a boxed warning to highlight the potential increased risk of CV events, and the well known risk of serious, and potentially life-threatening, stomach bleeding. The FDA has also requested that the package insert for all NSAIDs be revised to state that patients who have just had heart surgery should not take these medicines.

Some examples of other NSAIDs are:

• Ibuprofen (Motrin, Advil)
• Naproxen (Naprosyn, Aleve)
• Diclofenac (Voltaren, Cataflam)
• Ketoprofen (Orudis)

History

Celecoxib is manufactured as Celebrex in the United States by Pfizer. FDA approval was granted in 1998.

Controversy

Celecoxib and rofecoxib were the first of the COX-2 agents to gain FDA approval. They were very effective and quickly became the most widely prescribed NSAIDs in the United States. One of the drugs' largest appeals was the combination of effectiveness and lack of gastrointestinal side effects.

Within months of rofecoxib's approval in May 1999, the Vioxx Gastrointestinal Outcomes Research (VIGOR) trial reported a 50% reduction in serious gastrointestinal outcomes, but a 5-fold increase in thromboembolic cardiovascular events (primarily heart attack) among patients treated with 50 mg/day of rofecoxib compared with 1000 mg/day of naproxen. ^[2] Rofecoxib was voluntarily withdrawn from the market in September 2004.

A recent study from Durban, South Africa shows celecoxib to be safe and effective when used in patients with a low cardiovascular risk. ^[3]

A study from Australia in 2007 concurred with the use of celecoxib in low-risk patients. ^[4]

A review of randomized clinical trials failed to show an increased risk of cardiovascular complications with the use of celecoxib when compared to placebo or nonselective NSAIDS. ^[5]

Research

The following are areas of current interest with regard to celecoxib research:

• The use of celebrex in combination with risperidone was studied in new-onset schizophrenia. The study was done to address a theory that schizophrenia is related to an immune dysfunction. ^[6]
• The use of erlotinib and celecoxib in the treatment of non small-cell lung cancer. Celecoxib may slow the growth of a tumor by stopping blood flow to the tumor. Combining erlotinib with celecoxib may kill more tumor cells. ^[7]
• The effectiveness of celecoxib in treating a painful sore throat. ^[8]
• The interaction between aspirin and ibuprofen or celecoxib. ^[9]
• Studying the continuous or intermittent use of celecoxib in osteoarthritis. ^[10]
• The use of celecoxib vs the use of tramadol in the treatment of back pain. ^[11]

Clinical Trials

ClinicalTrials.gov has a list of ongoing trials available at: Celecoxib Trials

References

1. ↑ Pfizer web site. Celebrex (celecoxib capsules)
2. ↑ Bombardier C, Laine L, Reicin A, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med. 2000 Nov 23;343(21):1520-8. Abstract | Full Text
3. ↑ Moodley I. Review of the cardiovascular safety of COXIBs compared to NSAIDS. Cardiovasc J Afr. 2008 Mar-Apr;19(2):102-7. Abstract
4. ↑ Howes LG. Selective COX-2 inhibitors, NSAIDs and cardiovascular events - is celecoxib the safest choice? Ther Clin Risk Manag. 2007 Oct;3(5):831-45. Abstract
5. ↑ White WB, West CR, Borer JS. Risk of cardiovascular events in patients receiving celecoxib: a meta-analysis of randomized clinical trials. Am J Cardiol. 2007 Jan 1;99(1):91-8. Epub 2006 Nov 10. Abstract
6. ↑ Akhondzadeh S, Tabatabaee M, Amini H, Ahmadi Abhari SA, Abbasi SH, Behnam B. Celecoxib as adjunctive therapy in schizophrenia: a double-blind, randomized and placebo-controlled trial. Schizophr Res. 2007 Feb;90(1-3):179-85. Epub 2007 Jan 8. Abstract
7. ↑ Fidler MJ, Argiris A, Patel JD, et al. The potential predictive value of cyclooxygenase-2 expression and increased risk of gastrointestinal hemorrhage in advanced non-small cell lung cancer patients treated with erlotinib and celecoxib. Clin Cancer Res. 2008 Apr 1;14(7):2088-94. Abstract
8. ↑ ClinicalTrials.gov. Testing The Effectiveness Of Celecoxib In Patients With Painful Sore Throat.
9. ↑ Gladding PA, Webster MW, Farrell HB, Zeng IS, Park R, Ruijne N. The antiplatelet effect of six non-steroidal anti-inflammatory drugs and their pharmacodynamic interaction with aspirin in healthy volunteers. Am J Cardiol. 2008 Apr 1;101(7):1060-3. Epub 2008 Feb 6. Abstract
10. ↑ ClinicalTrials.gov. Study Of "Continuous Use" Of Celecoxib Vs. "Usual or Intermittent Use"
11. ↑ ClinicalTrials.gov. Celebrex vs Tramadol in the Treatment of Chronic Lower Back Pain.

External Links

Medline Plus: Celecoxib