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Etoricoxib



Etoricoxib
Systematic (IUPAC) name
5-chloro-6'-methyl-3-[4-(methylsulfonyl)phenyl]-
2,3'-bipyridine
Identifiers
CAS number 202409-33-4
ATC code M01AH05
PubChem 123619
Chemical data
Formula C18H15ClN2O2S 
Mol. mass 358.842 g/mol
Pharmacokinetic data
Bioavailability 100%
Protein binding 92%
Metabolism Hepatic, CYP extensively involved (mainly CYP3A4)
Half life 22 hours
Excretion Renal (70%) and fecal (20%)
Therapeutic considerations
Pregnancy cat.

Not recommended

Legal status

POM(UK)

Routes Oral

Etoricoxib (brand name Arcoxia worldwide; also Algix and Tauxib in Italy) is a new COX-2 selective inhibitor (approx. 106.0 times more selective for COX-2 inhibition over COX-1) from Merck & Co. Doses are 60, 90 mg/day for chronic pain and 120 mg/day for acute pain. Currently it is approved in more than 60 countries worldwide but not in the US, where the Food and Drug Administration (FDA) require additional safety and efficacy data for etoricoxib before it will issue approval. Current therapeutic indications are: treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, chronic low back pain, acute pain and gout. Note that approved indications differ by country.

Additional recommended knowledge

Like any other COX-2 selective inhibitor, Etoricoxib selectively inhibits isoform 2 of cyclo-oxigenase enzyme (COX-2). This reduces the generation of prostaglandins (PGs) from arachidonic acid. Among the different functions exerted by PGs, their role in the inflammation cascade should be highlighted. COX-2 selective inhibitor (aka "COXIB") showed less marked activity on type 1 cycloxigenase compared to traditional non-steroidal anti-inflammatory drugs (NSAID). This reduced activity is the cause of reduced gastrointestinal toxicity, as demonstrated in several large clinical trials performed with different COXIB (see below links on NEJM and The Lancet).

Some clinical trials and meta-analysis showed that treatment with COXIB led to increased incidence of adverse cardiovascular events compared to placebo. Because of these results, some molecules were withdrawn from the market (Rofecoxib, September 2004 and Valdecoxib, April 2005). In addition, the FDA and EMEA (USA and European Community Health Authorities respectively) started a revision process of the entire class of both NSAID and COX-2 inhibitors.

FDA concluded its revision on April 6, 2005: the final document can be found at: http://www.fda.gov/cder/drug/infopage/COX2/NSAIDdecisionMemo.pdf

EMEA concluded its revision on June 27, 2005: the final document can be found at: http://www.emea.europa.eu/pdfs/human/press/pr/20776605en.pdf

On April 27, 2007, the Food and Drug Administration issued Merck a "non-approvable letter" for Arcoxia. The letter said Merck needs to provide more test results showing that Arcoxia's benefits outweigh its risks before it has another chance of getting approved.



 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Etoricoxib". A list of authors is available in Wikipedia.
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