Celebrex - Celecoxib

Cydooxygenase-2 inhibitors Celecoxib (Celebrex) 11 Initial 400 followed by another 400... 

Celecoxib (Celebrex ) Cox 2 inhibitor Decrease in polyps in patients with familial polyposis Phase III... 

COX-2 Inhibitor Celecoxib (Celebrex, Pfizer) inhibits the enzyme COX-2, which is involved in pain and inflammation, but it has no effect on the COX-1 enzyme, which helps to maintain stomach lining. It is prescribed for the relief of pain and symptoms of osteoarthritis and rheumatoid arthritis. Previously, nonsteroidal anti-inflammatory drugs (NSAIDs) were used. NSAIDs inhibit both COX-1 and COX-2 enzymes and cause stomach bleeding (see Case Study 2). 

Aspirin is one of the most important NSAIDs because it decreases pain at predominantly peripheral sites with little cortical interaction and thus has few CNS effects. The prototypical COX-2 inhibitors are celecoxib (Celebrex) and its chemical cousin, rofecoxib (Vioxx). In addition to a role in inflammatory processes,... 

Celecoxib (Celebrex) and rofecoxib (Vioxx) are the two available COX-2 inhibitors. Both lack a carboxylic group present in most NSAIDs and therefore are able to orient into the COX-2 enzyme in a selective manner that differs from that of other NSAIDs. They have low aqueous solubility that prevents parenteral administration. 

Celecoxib (Celebrex) and rofecoxib (Vioxx) are highly selective COX-2 inhibitors. Because of this, they produce less erosion of the GI mucosa and cause less inhibition of platelet aggregation than do the nonselective COX inhibitors. Short-term (6 months-to a year) clinical trials have shown that celecoxib and rofecoxib produce less GI toxicity than nonselective NSAIDs. However, serious GI bleeding and ulceration have occurred in patients taking these drugs, and long-term prospective studies of their safety have yet to be completed. Like the nonselective NSAIDs, the selective COX-2 inhibitors can produce renal side effects such as hypertension and edema. 

Chapter 2. Anti-inflammatory Cyclooxygenase-2 Selective Inhibitors Celecoxib (Celebrex ) and Rofecoxib (Vioxx )... 

The CLASS study published in fAMA in 2000 appeared to confirm the gastrointestinal protective effects of celecoxib (Celebrex ) over traditional NSAIDs after six months of treatment (Silverstein et al. 2000). However, material on the website of the FDA revealed a number of discrepancies between the data as published in fAMA and those submitted to the FDA. The published trial actually combined the results of two trials, one that continued for twelve months and the second which ran for 16 months. At 12-16 months there was no difference in gastrointestinal adverse effects between the celecoxib and traditional NSAID groups (Hrachovec and Mora 2001 Wright et al. 2001). 

Celecoxib (Celebrex) Diclofenac (Cataflam, Flector, Voltaren) Diflunisal (Dolobid) Etodolac... 

At the time of this writing, celecoxib (Celebrex) is the only COX-2 selective drug that is still available. It will be interesting to see if new COX-2 drugs can be developed that have an acceptable cardiovascular risk profile. Likewise, efforts continue to clearly identify patients who should not take these drugs because of an increased risk for heart attack or ischemic stroke. 

Drugs specifically designed for COX-2 selectivity have been marketed quite successfully, especially in the United States. The drugs that were part of this litigation were celecoxib (Celebrex ) and valdecoxib (Bextra ). COX-2 selective inhibitors have been shrouded in controversy since their use has been in some cases linked with increased risk of heart attacks and stroke. Celebrex and Bextra were both marketed by Pfizer, but Bextra was pulled from the United States market in 2005 out of safety concerns. The COX-2 selective inhibitor rofecoxib (Vioxx ) was marketed by Merck and was voluntarily pulled from the market by Merck in 2004. Celebrex remains on the market, and worldwide sales in 2007 were over 2 billion. 

Ongoing research led to the development of COX-2 selective inhibitors (e.g., rofecoxib and celecoxib). Celecoxib (Celebrex ) was approved by the FDA in 1998 to treat osteoarthritis and rheumatoid arthritis. Rofecoxib (Vioxx ) was approved in May 1999 to treat osteoarthritis, acute pain, and dysmenorrhea. Sales for the two drugs in 1999 were 1.5 billion and 373 million, respectively. Clinical studies have indicated a significant reduction in GI perforation, ulceration, or bleeding with the COX-2 inhibitors. The recognition of multiple COX isoforms has had one of the greatest impacts on the development of NSAIDs since the original synthesis of aspirin more than a century ago. 

The diaryl pyrazole derivative celecoxib (Celebrex /Pharmacia, Pfizer), the fiiranone derivative rofecoxib (Vioxx /Merck), and the isoxazole derivative valdecoxib (Bextra /... 

McMorran M, Morawiecka I. Celecoxib (Celebrex) 1 year later. CMAJ 2000 162(7) 1044-61048-50. 

Wooltorton E. What s all the fuss Safety concerns abont COX-2 inhibitors rofecoxib (Vioxx) and celecoxib (Celebrex). CMAJ 2002 166(13) 1692-3. 

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