Etoricoxib

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Etoricoxib
Systematic (IUPAC) name
5-chloro-6'-methyl-3-[4-(methylsulfonyl)phenyl]-
2,3'-bipyridine
Clinical data
AHFS/Drugs.comInternational Drug Names
Pregnancy cat.Not recommended
Legal statusPOM (UK)
RoutesOral
Pharmacokinetic data
Bioavailability100%
Protein binding92%
MetabolismHepatic, CYP extensively involved (mainly CYP3A4)
Half-life22 hours
ExcretionRenal (70%) and fecal (20%)
Identifiers
CAS number202409-33-4 YesY
ATC codeM01AH05
PubChemCID 123619
DrugBankDB01628
ChemSpider110209 YesY
UNIIWRX4NFY03R YesY
KEGGD03710 YesY
ChEBICHEBI:6339 YesY
ChEMBLCHEMBL416146 YesY
Chemical data
FormulaC18H15ClN2O2S 
Mol. mass358.842 g/mol
 YesY (what is this?)  (verify)
 
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Etoricoxib
Systematic (IUPAC) name
5-chloro-6'-methyl-3-[4-(methylsulfonyl)phenyl]-
2,3'-bipyridine
Clinical data
AHFS/Drugs.comInternational Drug Names
Pregnancy cat.Not recommended
Legal statusPOM (UK)
RoutesOral
Pharmacokinetic data
Bioavailability100%
Protein binding92%
MetabolismHepatic, CYP extensively involved (mainly CYP3A4)
Half-life22 hours
ExcretionRenal (70%) and fecal (20%)
Identifiers
CAS number202409-33-4 YesY
ATC codeM01AH05
PubChemCID 123619
DrugBankDB01628
ChemSpider110209 YesY
UNIIWRX4NFY03R YesY
KEGGD03710 YesY
ChEBICHEBI:6339 YesY
ChEMBLCHEMBL416146 YesY
Chemical data
FormulaC18H15ClN2O2S 
Mol. mass358.842 g/mol
 YesY (what is this?)  (verify)

Etoricoxib (brand name Arcoxia worldwide; also Algix and Tauxib in Italy, Nucoxia in India) is a COX-2 selective inhibitor (approx. 106.0 times more selective for COX-2 inhibition over COX-1) from Merck & Co. 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 ("coxib"), etoricoxib selectively inhibits isoform 2 of the enzyme cyclo-oxigenase (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 inhibitors 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 side effects, as demonstrated in several large clinical trials performed with different coxibs.[1][2]

Some clinical trials and meta-analysis showed that treatment with some coxibs (in particular rofecoxib) led to increased incidence of adverse cardiovascular events compared to placebo. Because of these results, some drugs were withdrawn from the market (rofecoxib, in September 2004 and valdecoxib in April 2005). In addition, the FDA and EMA (USA and European Community health authorities respectively) started a revision process of the entire class of both NSAID and COX-2 inhibitors.

The FDA concluded its revision on April 6, 2005: the final document can be found here.

The EMA concluded its revision on June 27, 2005: the final document can be found here.

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

References