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Celecoxib

Celecoxib (INN) is a non-steroidal anti-inflammatory drug (NSAID) used in the treatment of osteoarthritis, rheumatoid arthritis, acute pain, painful menstruation and menstrual symptoms, and to reduce numbers of colon and rectum polyps in patients with familial adenomatous polyposis.

It is marketed by Pfizer under the brand name Celebrex. In some countries, it is branded Celebra.

Pharmacology

Celecoxib is a highly selective COX-2 inhibitor and primarily inhibits this isoform of cyclooxygenase, whereas traditional NSAIDs inhibit both COX-1 and COX-2. Celecoxib is approximately 10-20 times more selective for COX-2 inhibition over COX-1. In theory, this specificity allows celecoxib and other COX-2 inhibitors to reduce inflammation (and pain) while minimizing gastrointestinal adverse drug reactions (eg. stomach ulcers) that are common with non-selective NSAIDs. It also means that it has a reduced effect on platelet aggregation compared to traditional NSAIDs.

Adverse effects

Aside from the incidence of gastric ulceration, celecoxib exhibits a similar adverse drug reaction (ADR) profile to other NSAIDs.

Recently in a large study published in JAMA 2006, Celecoxib appears less adverse for renal (kidney) disease and heart arrhythmia compared to Vioxx. Systematic review of adverse renal and arrhythmia risk of celecoxib and other COX-2 inhibitors, in JAMA 2006

Gastrointestinal ADRs

In theory the COX-2 selectivity should result in a significantly lower incidence of gastrointestinal ulceration than traditional NSAIDs. The main body of evidence touted to support this theory were the preliminary (6 month) results of the Celecoxib Long-term Arthritis Safety Study (CLASS) as published in 2000, which demonstrated a significant reduction in the incidence of gastrointestinal ulceration in those taking celecoxib versus ibuprofen or diclofenac. (Silverstein et al, 2000) The final (12 month) results from the CLASS study, however, did not indicate any advantage of celecoxib over the other NSAIDs in the study. (Malhotra, Shafiq & Pandhi, 2004)

Cardiovascular risk

The withdrawal of rofecoxib from the market in 2004 due to an increased risk of adverse cardiovascular events led to the suspicion that this was a class effect. Indeed an increased risk of heart attack and stroke was found in a National Cancer Institute study studying the use of 400-800 mg celecoxib daily for the prevention of colorectal adenoma (relative risk 2.3-3.4 vs placebo). (Solomon et al., 2005)

There is still much conjecture, however, as to whether this risk is significant for the majority of patients being treated with lower doses for osteoarthritis. The overall safety profile of celecoxib, including its cardiovascular, renal and digestive effects, will be compared to traditional anti-inflammatories (naproxen and ibuprofen) in a randomized trial of 20,000 high risk patients that is due to begin in 2006 (PRECISION study sponsored by Pfizer)

A recent meta-analysis of all trials comparing non-steroidal anti-inflammatory drugs found a 80% increase in the risk of myocardial infarction with both newer Cox-2 antagonists and high dose traditional anti-inflammatories compared with placebo, with the important exception of naproxen, which was not associated with an increased cardiovascular risk (Kearney et al, BMJ 2006;332:1302-1308).

Allergy

Celecoxib contains a sulfonamide moiety and may cause allergic reactions in those allergic to other sulfonamide-containing drugs. This is in addition to the contraindication in patients with severe allergies to other NSAIDs.

Celecoxib is available by prescription in capsule form.


 

Source: wikipedia GFDL

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Page last modified: May 2008


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