Etoricoxib

From Wikipedia, the free encyclopedia


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	C₁₈H₁₅Cl N₂O₂S
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 seletive 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 is approved in more than 60 countries worldwide but not in the US, where the Food and Drug Administration (FDA) required additional safety and efficacy data for etoricoxib before it will issue approval. Current therapeutic indications are: treatment of rheumatoid arthritis, osteoarthritis, chronic low back pain, gout, and ankylosing spondylitis, acute pain. Note that approved indications differ country by country.

Like any other COX-2 selective inhibitor Etoricoxib selectively inhibits isoform 2 of cyclo-oxigenase enzyme (COX-2). This reduce prostaglandins (PGs) generation from arachidonic acid. Among the different functions exerted by PGs, it should be highlighted their role in the inflammation cascade. 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 lead to increased incidence of cardiovascular adverse events compared to placebo. Because of these results, some molecules were withdrawn from the market (Rofecoxib, September 2004 and Valdecoxib April 2005). In addition, FDA and EMEA, respectively USA and European Community Health Authorities, started a revision process of the entire class of both NSAID and COX-2 inhibitors.

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

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