Etoricoxib

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Etoricoxib
Etoricoxib structural formula V.1.svg
Systematic (IUPAC) name
5-Chloro-6'-methyl-3-[4-(methylsulfonyl)phenyl]-2,3'-bipyridine
Clinical data
AHFS/Drugs.com International Drug Names
Pregnancy
category
  • Not recommended
Routes of
administration
Oral
Legal status
Legal status
  • AU: S4 (Prescription only)
  • 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 YesY
ATC code M01AH05 (WHO)
PubChem CID 123619
IUPHAR/BPS 2896
DrugBank DB01628 YesY
ChemSpider 110209 YesY
UNII WRX4NFY03R YesY
KEGG D03710 YesY
ChEBI CHEBI:6339 YesY
ChEMBL CHEMBL416146 YesY
Chemical data
Formula C18H15ClN2O2S
Molar mass 358.842 g/mol
  (verify)

Etoricoxib (Arcoxia) is a selective COX-2 inhibitor 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) has required additional safety and efficacy data for etoricoxib before it will issue approval.

Therapeutic indications[edit]

Etoricoxib is indicated for the treatment of rheumatoid arthritis, psoriatic arthritis, osteoarthritis, ankylosing spondylitis, chronic low back pain, acute pain, and gout. Approved indications differ by country.

A Cochrane systematic review assessed the benefits of single-dose etoricoxib in reduction of acute post-operative pain in adults.[1] Single-dose oral etoricoxib provides good quality pain relief post-operatively in adults and adverse events are similar to placebo in the studies included.[1] Etoricoxib given at a dose of 120 mg is as effective or even better than other analgesics that are commonly used.[1]

Mechanism of action[edit]

Like any other selective COX-2 inhibitor ("coxib"), etoricoxib selectively inhibits isoform 2 of the enzyme cyclooxygenase (COX-2). It has approximately 106-fold selectivity for COX-2 inhibition over COX-1. 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.

Selective COX-2 inhibitors show less activity on COX-1 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.[2][3]

Adverse Effects[edit]

Like all other NSAIDs the COX-2 inhibitors too have their share of adverse effects. Fixed drug eruption and generalised erythema,[4] Acute generalized exanthematous pustulosis (AGEP),[5] erythema multiforme like eruption[6] and drug induced pretibial erythema[7] are some serious side effects reported, besides the usual innocuous ones.

History[edit]

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 United States Food and Drug Administration and the European Medicines Agency started revision processes of the entire class of both NSAIDs and COX-2 inhibitors.[8]

In April 2007, the FDA 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.

Brand names[edit]

Brand names for etoricoxib include Arcoxia in Sweden, Finland, Estonia, Germany, Lithuania, Ireland, Israel, Brazil, Singapore, Thailand, Guatemala, Mexico, Bulgaria, Philippines, Romania and United Kingdom; Algix and Tauxib in Italy; Etorix, Tory and Vargus in Bangladesh; Berrica and Starcox in Pakistan; Exxiv in Portugal; Etozox in India; Kingdom of Saudi Arabia

References[edit]

  1. ^ a b c Clarke R, Derry S, Moore RA; Derry; Moore (2014). "Single dose oral etoricoxib for acute postoperative pain in adults". Cochrane Database Syst Rev. 5 (5): CD004309. doi:10.1002/14651858.CD004309.pub4. PMID 24809657. 
  2. ^ Bombardier, Claire; Laine, Loren; Reicin, Alise; Shapiro, Deborah; Burgos-Vargas, Ruben; Davis, Barry; Day, Richard; Ferraz, Marcos Bosi; Hawkey, Christopher J.; Hochberg, Marc C.; Kvien, Tore K.; Schnitzer, Thomas J. (2000). "Comparison of Upper Gastrointestinal Toxicity of Rofecoxib and Naproxen in Patients with Rheumatoid Arthritis". New England Journal of Medicine. 343 (21): 1520–8, 2 p following 1528. doi:10.1056/NEJM200011233432103. PMID 11087881. 
  3. ^ Cannon, Christopher P; Curtis, Sean P; Fitzgerald, Garret A; Krum, Henry; Kaur, Amarjot; Bolognese, James A; Reicin, Alise S; Bombardier, Claire; Weinblatt, Michael E; Van Der Heijde, Désirée; Erdmann, Erland; Laine, Loren (2006). "Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: A randomised comparison". The Lancet. 368 (9549): 1771–1781. doi:10.1016/S0140-6736(06)69666-9. 
  4. ^ Augustine M, Sharma P, Stephen J, Jayaseelan E. Fixed drug eruption and generalised erythema following etoricoxib. Indian J Dermatol Venereol Leprol. 2006;72:307–9. http://www.ijdvl.com/text.asp?2006/72/4/307/26732
  5. ^ Makela, L; Lammintausta, K (2008). "Etoricoxib-induced acute generalized exanthematous pustulosis". Acta Derm Venereol. 88: 200–1. doi:10.2340/00015555-0381. 
  6. ^ Thirion, L; Nikkels, AF; Piérard, GE (2008). "Etoricoxib-induced erythema-multiforme-like eruption". Dermatology. 216: 227–8. doi:10.1159/000112930. 
  7. ^ Kumar, P (2015). "Etoricoxib-induced pretibial erythema and edema". Indian Dermatol Online J. 6: S47–9. doi:10.4103/2229-5178.171046. PMC 4738517free to read. PMID 26904451. 
  8. ^ 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 Archived April 6, 2008, at the Wayback Machine.