Etoricoxib

Etoricoxib, sold under the trade name Arcoxia, is a selective COX-2 inhibitor from McOLSON Research Laboratories. 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.

Etoricoxib
Clinical data
AHFS/Drugs.comInternational Drug Names
Pregnancy
category
  • AU: C
  • Not recommended
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
Pharmacokinetic data
Bioavailability100%
Protein binding92%
MetabolismHepatic, CYP extensively involved (mainly CYP3A4)
Elimination half-life22 hours
ExcretionRenal (70%) and fecal (20%)
Identifiers
IUPAC name
  • 5-Chloro-6'-methyl-3-[4-(methylsulfonyl)phenyl]-2,3'-bipyridine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.207.709
Chemical and physical data
FormulaC18H15ClN2O2S
Molar mass358.84 g·mol−1
3D model (JSmol)
SMILES
  • O=S(=O)(c3ccc(c2cc(Cl)cnc2c1cnc(cc1)C)cc3)C
InChI
  • InChI=1S/C18H15ClN2O2S/c1-12-3-4-14(10-20-12)18-17(9-15(19)11-21-18)13-5-7-16(8-6-13)24(2,22)23/h3-11H,1-2H3 Y
  • Key:MNJVRJDLRVPLFE-UHFFFAOYSA-N Y
  (verify)

It was patented in 1996 and approved for medical use in 2002.[1]

Medical uses

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. In the U.K. and Germany, it is also "used for the short term treatment of moderate pain after dental surgery" of adults.[2]

Efficacy

A Cochrane review assessed the benefits of single-dose etoricoxib in reduction of acute post-operative pain in adults.[3] Single-dose oral etoricoxib provides four times more pain relief post-operatively than placebo, with equivalent levels of adverse events.[3] Etoricoxib given at a dose of 120 mg is as effective or even better than other analgesics that are commonly used.[3]

Adverse effects

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.

Mechanism of action

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.[8][9]

History

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.[10]

Brand names

Brand names for etoricoxib include:

  • Algix and Tauxib in Italy
  • Anexia in Colombia
  • Arcox, Berrica, and Starcox Etoxib in Pakistan
  • Arcoxia in Australia, Brazil, Bulgaria, Chile, China, Colombia, Costa Rica, Croatia, Ecuador, Egypt, Estonia, Finland, Georgia, Greece, Guatemala, Hong Kong, Hungary, Indonesia, Ireland, Israel, Italy, Jordan, Lebanon, Lithuania, Luxembourg, Malaysia, Mexico, Morocco, Netherlands, New Zealand, Norway, Panama, Philippines, Poland, Portugal, Romania, Russian Federation, Saudi Arabia, Serbia, Singapore, South Africa, Spain, Sweden, Taiwan, Thailand, The Bahamas, Trinidad & Tobago, United Arab Emirates, United Kingdom and Ukraine.
  • Atocib in Vietnam
  • Dolicox in Morocco
  • Dolocox in Argentina
  • Coxit in Jordan
  • Dabie in Singapore
  • Doloxib in Poland
  • E-Cox and Vecoxib in Nepal
  • Eberil in Thailand
  • Erciba in Greece
  • Etoll, Etoshine, Nucoxia in India
  • Etoricoxib in Germany
  • Etorix, Eto, Tory, Etoxib, and Vargus in Bangladesh and Costa Rica
  • Etozox, Etospeed, Intacoxia, Nucoxia, ETOS MR, and Etoshine in India
  • Exinef in Singapore and South Africa
  • Exxiv in Portugal
  • Foldox in Argentina[11] and Paraguay
  • Gerocoxan in Romania
  • Hetori in Brazil
  • Kostarox in Poland
  • Roticox in Poland
  • Berica in Pakistan
  • Xumer in Peru

References
  1. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 522. ISBN 9783527607495.
  2. Arcoxia Etoricoxib 3882 UK (70054693/001 ed.). Merck Sharp & Dohme. February 2018. pp. 1–2.
  3. Clarke R, Derry S, Moore RA (May 2014). "Single dose oral etoricoxib for acute postoperative pain in adults". The Cochrane Database of Systematic Reviews (5): CD004309. doi:10.1002/14651858.CD004309.pub4. PMC 6485336. PMID 24809657.
  4. Augustine M, Sharma P, Stephen J, Jayaseelan E (2006). "Fixed drug eruption and generalised erythema following etoricoxib". Indian Journal of Dermatology, Venereology and Leprology. 72 (4): 307–9. doi:10.4103/0378-6323.26732. PMID 16880582.
  5. Mäkelä L, Lammintausta K (2008). "Etoricoxib-induced acute generalized exanthematous pustulosis". Acta Dermato-Venereologica. 88 (2): 200–1. doi:10.2340/00015555-0381. PMID 18311467.
  6. Thirion L, Nikkels AF, Piérard GE (2008). "Etoricoxib-induced erythema-multiforme-like eruption". Dermatology. 216 (3): 227–8. doi:10.1159/000112930. PMID 18182814. S2CID 207645594.
  7. Kumar P (December 2015). "Etoricoxib-induced pretibial erythema and edema". Indian Dermatology Online Journal. 6 (Suppl 1): S47-9. doi:10.4103/2229-5178.171046. PMC 4738517. PMID 26904451.
  8. Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, et al. (November 2000). "Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group". The New England Journal of Medicine. 343 (21): 1520–8, 2 p following 1528. doi:10.1056/NEJM200011233432103. PMID 11087881.
  9. Cannon CP, Curtis SP, FitzGerald GA, Krum H, Kaur A, Bolognese JA, et al. (November 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". Lancet. 368 (9549): 1771–81. doi:10.1016/S0140-6736(06)69666-9. PMID 17113426. S2CID 18464206.
  10. 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
  11. "Foldox". sidus.com.ar (in Spanish). Retrieved 13 March 2019.
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