Etoricoxib

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.

Etoricoxib
Clinical data
AHFS/Drugs.comInternational Drug Names
Pregnancy
category
  • Not recommended
Routes of
administration		Oral
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
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)
  (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.

A Cochrane review assessed the benefits of single-dose etoricoxib in reduction of acute post-operative pain in adults.[2] Single-dose oral etoricoxib provides four times more pain relief post-operatively than placebo, with equivalent levels of adverse events.[2] Etoricoxib given at a dose of 120 mg is as effective or even better than other analgesics that are commonly used.[2]

Adverse effects

Like all other NSAIDs the COX-2 inhibitors too have their share of adverse effects. Fixed drug eruption and generalised erythema,[3] acute generalized exanthematous pustulosis (AGEP),[4] erythema multiforme like eruption[5] and drug induced pretibial erythema[6] 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.[7][8]

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.[9]

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

Brand names for etoricoxib include:

  • Arcoxia in Spain, Portugal, Egypt, Saudi Arabia, Sweden, Finland, Norway, Estonia, Germany, Greece, Lithuania, Chile, China, Hong Kong, Hungary, Indonesia, Ireland, Israel, Jordan, Lebanon, Brazil, Malaysia, Singapore, Thailand, Guatemala, Mexico, Bulgaria, Costa Rica, Philippines, Ecuador, Australia, New Zealand, Romania, South Africa, Trinidad & Tobago, United Arab Emirates, United Kingdom, The Bahamas, Ukraine, Russian Federation, Netherlands, Croatia, Serbia, Colombia and Panama
  • Algix and Tauxib in Italy
  • Blokium Cox in Argentina
  • Etorix, Eto, Tory, Etoxib, and Vargus in Bangladesh and Costa Rica
  • Arcox, Berrica, and Starcox in Pakistan
  • Exxiv in Portugal
  • Etozox, Etospeed, Intacoxia, Nucoxia, ETOS MR, and Etoshine in India
  • Foldox in Argentina[10] and Paraguay
  • Coxit in Jordan
  • E-Cox and Vecoxib in Nepal
  • Hetori in Brazi
  • Etoll in India
  • Dabie in Singapore
  • Gerocoxan in Romania

References
  1. Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 522. ISBN 9783527607495.
  2. Clarke, Rachel; Derry, Sheena; Moore, R Andrew (2014). "Single dose oral etoricoxib for acute postoperative pain in adults". Cochrane Database of Systematic Reviews (5): CD004309. doi:10.1002/14651858.CD004309.pub4. PMC 6485336. PMID 24809657.
  3. 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
  4. Makela, L; Lammintausta, K (2008). "Etoricoxib-induced acute generalized exanthematous pustulosis". Acta Derm Venereol. 88 (2): 200–1. doi:10.2340/00015555-0381. PMID 18311467.
  5. Thirion, L; Nikkels, AF; Piérard, GE (2008). "Etoricoxib-induced erythema-multiforme-like eruption". Dermatology. 216 (3): 227–8. doi:10.1159/000112930. PMID 18182814.
  6. Kumar, P (2015). "Etoricoxib-induced pretibial erythema and edema". Indian Dermatol Online J. 6 (Suppl 1): S47–9. doi:10.4103/2229-5178.171046. PMC 4738517. PMID 26904451.
  7. 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.
  8. 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. PMID 17113426.
  9. 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
  10. "Foldox". sidus.com.ar (in Spanish). Retrieved 2019-03-13.
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