parecoxib

{{Short description|Type of nonsteroidal anti-inflammatory drug}}

{{Drugbox

| Verifiedfields = changed

| verifiedrevid = 464197422

| image = Parecoxib.svg

| image_class = skin-invert-image

| pronounce =

| tradename =

| Drugs.com = {{drugs.com|international|parecoxib}}

| MedlinePlus =

| DailyMedID =

| pregnancy_AU = C

| pregnancy_AU_comment =

| pregnancy_category =

| routes_of_administration = Intravenous, intramuscular

| class =

| ATC_prefix = M01

| ATC_suffix = AH04

| ATC_supplemental =

| legal_AU = S4

| legal_AU_comment =

| legal_BR = C1

| legal_BR_comment = {{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=Diário Oficial da União |language=pt-BR |publication-date=2023-04-04}}

| legal_CA =

| legal_CA_comment =

| legal_DE =

| legal_DE_comment =

| legal_NZ =

| legal_NZ_comment =

| legal_UK = POM

| legal_UK_comment =

| legal_US =

| legal_US_comment =

| legal_EU = Rx-only

| legal_EU_comment = {{cite web | title=Dynastat EPAR | website=European Medicines Agency | date=22 March 2002 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/dynastat | access-date=2 January 2024}}

| legal_UN =

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| legal_status =

| bioavailability = 100%

| protein_bound = 98%

| metabolism = Liver to valdecoxib and propionic acid
CYP extensively involved (mainly CYP3A4 and 2C9)

| elimination_half-life = 22 minutes (parecoxib)
8 hours (valdecoxib)

| excretion = Kidney (70%, metabolites)

| IUPHAR_ligand = 2895

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 198470-84-7

| PubChem = 119828

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB08439

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 106990

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 9TUW81Y3CE

| ChEBI_Ref = {{ebicite|changed|EBI}}

| ChEBI = 73038

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 1206690

| IUPAC_name = N-{[4-(5-methyl-3-phenylisoxazol-4-yl)phenyl]
sulfonyl}propanamide

| C=19 | H=18 | N=2 | O=4 | S=1

| smiles = O=C(NS(=O)(=O)c3ccc(c2c(onc2c1ccccc1)C)cc3)CC

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C19H18N2O4S/c1-3-17(22)21-26(23,24)16-11-9-14(10-12-16)18-13(2)25-20-19(18)15-7-5-4-6-8-15/h4-12H,3H2,1-2H3,(H,21,22)

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = TZRHLKRLEZJVIJ-UHFFFAOYSA-N

}}

Parecoxib, sold under the brand name Dynastat among others, is a water-soluble and injectable prodrug of valdecoxib. Parecoxib is a COX2 selective inhibitor. It is injectable. It is approved in the European Union for short term perioperative pain control.

It was patented in 1996 and approved for medical use in 2002.{{cite book | vauthors = Fischer J, Ganellin CR |title= Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=522 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA522 |language=en}}

Approval

In 2005, the US Food and Drug Administration (FDA) issued a letter of non-approval for parecoxib in the United States. No reasons were ever documented publicly for the non-approval, although one study noted increased occurrences of heart attacks following cardiac bypass surgery compared to placebo when high doses of parecoxib were used to control pain after surgery. Importantly, rare but severe allergic reactions (Stevens–Johnson syndrome, Lyell syndrome) have been described with valdecoxib, the molecule to which parecoxib is converted.Health {{cite web | title = Association of Bextra (Valdecoxib) with Serious Adverse Drug Reactions | date = April 21, 2005 | url = https://www.healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2005/14311a-eng.php | work = Health Canada }} The drug is not approved for use after cardiac surgery in Europe.

All anti-inflammatory medications in the US carry the same warning regarding skin reactions, and none are approved for use during CABG surgery, so the reason for the FDA denying the approval of parecoxib remains unknown, but was likely related to political pressure from the US Congress to not approve another COX-2 selective inhibitor in the wake of the Vioxx affair. No COX-2 selective inhibitor has been approved in the US since that time, regardless of the safety profile of parecoxib in Europe. Efforts to find out the scientific rationale, or more likely the lack thereof, that the FDA used to justify the non-approval of parecoxib in the USA have proven futile due to secrecy issues.{{cite journal | vauthors = Gajraj NM | title = COX-2 inhibitors celecoxib and parecoxib: valuable options for postoperative pain management | journal = Current Topics in Medicinal Chemistry | volume = 7 | issue = 3 | pages = 235–49 | date = 2007 | pmid = 17305567 | doi = 10.2174/156802607779941323 }}{{cite web | vauthors= Kiehl S | title= Secrecy on the Rise | work= The Baltimore Sun | date= March 13, 2005 | url= http://www.baltimoresun.com/news/opinion/oped/bal-pe.sunshine13mar13,0,7054066.story | access-date= July 27, 2013 | archive-date= May 30, 2013 | archive-url= https://web.archive.org/web/20130530121504/http://www.baltimoresun.com/news/opinion/oped/bal-pe.sunshine13mar13,0,7054066.story | url-status= dead }}

The political motivation to not approve parecoxib was further supported by a 2017 pooled analysis of safety data in 28 published studies, which showed after 69,567,300 units of parecoxib, skin rash and cardiac complications were minimal, if at all, different from placebo.{{cite journal | vauthors = Schug SA, Parsons B, Li C, Xia F | title = The safety profile of parecoxib for the treatment of postoperative pain: a pooled analysis of 28 randomized, double-blind, placebo-controlled clinical trials and a review of over 10 years of postauthorization data | journal = Journal of Pain Research | volume = 10 | pages = 2451–2459 | year = 2017 | pmid = 29066931 | pmc = 5644539 | doi = 10.2147/jpr.s136052 | doi-access = free }}

Parecoxib, along with other COX-2 selective inhibitors, celecoxib, valdecoxib, and mavacoxib, were discovered by a team at the Searle division of Monsanto led by John Talley.{{cite news| vauthors = Langreth R |title=The Chemical Cobbler |url= https://www.forbes.com/global/2003/0623/050.html |work=Forbes |date=June 23, 2003 }}{{cite journal|title=Dr. John Talley: 2001 St. Louis Awardee|journal=Chemical Bond |date=May 2001 |volume=52 |issue=5 |page=2 |url=http://www.stlacs.org/Bonds/2001May.pdf |publisher=St. Louis Section, American Chemical Society |archive-url = https://web.archive.org/web/20180415180802/http://www.stlacs.org/Bonds/2001May.pdf |archive-date=15 April 2018}}

Parecoxib is the first parenteral COX-2 selective inhibitor available for clinical use in pain management. Its first perceptible analgesic effect occurs within seven to thirteen minutes, with clinically meaningful analgesia demonstrated within twenty-three to thirty-nine minutes and a peak effect within two hours following administration of single doses of 40 mg by IV or IM injection.{{cite journal | vauthors = Mulita F, Karpetas G, Liolis E, Vailas M, Tchabashvili L, Maroulis I | title = Comparison of analgesic efficacy of acetaminophen monotherapy versus acetaminophen combinations with either pethidine or parecoxib in patients undergoing laparoscopic cholecystectomy: a randomized prospective study | journal = Medicinski Glasnik | volume = 18 | issue = 1 | pages = 27–32 | date = February 2021 | pmid = 33155461 | doi = 10.17392/1245-21 | doi-access = free }}

parecoxib

Approval

References

Further reading