Etoricoxib

Etoricoxib

File:Etoricoxib.svg
Systematic (IUPAC) name
5-chloro-6'-methyl-3-[4-(methylsulfonyl)phenyl]- 2,3'-bipyridine
Clinical data
Pregnancy category	Not recommended
Routes of administration	Oral
Legal status
Legal status	UK: POM (Prescription only)
Pharmacokinetic data
Bioavailability	100%
Protein binding	92%
Metabolism	Hepatic, CYP extensively involved (mainly CYP3A4)
Biological half-life	22 hours
Excretion	Renal (70%) and fecal (20%)
Identifiers
CAS Number	202409-33-4
ATC code	M01AH05 (WHO)
PubChem	CID 123619
ChemSpider	110209
Chemical data
Formula	C18H15ClN2O2S
Molar mass	358.842 g/mol[[]]
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Etoricoxib (brand name Arcoxia worldwide; also Algix and Tauxib in Italy) is a 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 70 countries worldwide but not in the US, where the Food and Drug Administration (FDA) requires additional safety and efficacy data for etoricoxib before it will issue approval. Current therapeutic indications are: treatment of rheumatoid arthritis, psoriatic arthritis, osteoarthritis, ankylosing spondylitis, chronic low back pain, acute pain and gout. Note that approved indications differ by country.

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 some COXIBs (in particular Vioxx, rofecoxib) 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 Because of these results, some molecules were withdrawn from the market (Rofecoxib, September 2004 and Valdecoxib, April 2005).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.

External links

• European Medicines Agency (EMEA) - Homepage - [1]
• US Food and Drug Administration (FDA) - Homepage - [2]
• (VIGOR study on The New England Journal of Medicine - NEJM)
• (MEDAL study on The Lancet)

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