|Systematic (IUPAC) name|
|Pregnancy cat.||Not recommended|
|Legal status||Prescription Only (S4) (AU) POM (UK)|
|Metabolism||Hepatic, CYP extensively involved (mainly CYP3A4)|
|Excretion||Renal (70%) and fecal (20%)|
|Mol. mass||358.842 g/mol|
|(what is this?)|
Etoricoxib (brand name Arcoxia worldwide; Coxyveen by Solmarc Lifesciences (P) Ltd and Nucoxia in India, also Algix and Tauxib in Italy, Vargus by Sandoz in Bangladesh Starcox By GETS Pharma in Pakistan) 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 80 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.
Mechanism of action
Like any other COX-2 selective inhibitor ("coxib"), etoricoxib selectively inhibits isoform 2 of the enzyme cyclo-oxygenase (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.
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 Because of these results, some drugs were withdrawn from the market (rofecoxib, in September 2004 and valdecoxib in April 2005).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.