Parecoxib

Last updated
Parecoxib
Parecoxib.svg
Clinical data
AHFS/Drugs.com International Drug Names
License data
Pregnancy
category
  • Not recommended
Routes of
administration
Intravenous and intramuscular
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • BR: Class C1 (Other controlled substances) [1]
  • UK: POM (Prescription only)
Pharmacokinetic data
Bioavailability 100%
Protein binding 98%
Metabolism Hepatic to valdecoxib and propionic acid
CYP extensively involved (mainly CYP3A4 and 2C9)
Elimination half-life 22 minutes (parecoxib)
8 hours (valdecoxib)
Excretion Renal (70%, metabolites)
Identifiers
  • N-{[4-(5-methyl-3-phenylisoxazol-4-yl)phenyl]
    sulfonyl}propanamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.230.078 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C19H18N2O4S
Molar mass 370.42 g·mol−1
3D model (JSmol)
  • O=C(NS(=O)(=O)c3ccc(c2c(onc2c1ccccc1)C)cc3)CC
  • InChI=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) Yes check.svgY
  • Key:TZRHLKRLEZJVIJ-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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 through much of Europe for short term perioperative pain control.

Contents

It was patented in 1996 and approved for medical use in 2002. [2]

Approval

In 2005, the U.S. 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. [3] The drug is not approved for use after cardiac surgery in Europe.

All anti-inflammatory medications in the U.S. 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. [4] [5]

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. [6]

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. [7] [8]

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. [9]

See also

Related Research Articles

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<span class="mw-page-title-main">Nonsteroidal anti-inflammatory drug</span> Class of therapeutic drug for relieving pain and inflammation

Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of use, but largely include an increased risk of gastrointestinal ulcers and bleeds, heart attack, and kidney disease.

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<span class="mw-page-title-main">Paracetamol</span> Common medication for pain and fever

Paracetamol is a non-opioid analgesic and antipyretic agent used to treat fever and mild to moderate pain. It is a widely used over the counter medication and common brand names include Tylenol and Panadol.

<span class="mw-page-title-main">Ibuprofen</span> Medication used for treating pain, fever, and inflammation

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arteriosus in a premature baby. It can be used orally or intravenously. It typically begins working within an hour.

<span class="mw-page-title-main">Rofecoxib</span> Nonsteroidal anti-inflammatory drug

Rofecoxib is a COX-2-selective nonsteroidal anti-inflammatory drug (NSAID). It was marketed by Merck & Co. to treat osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, acute pain conditions, migraine, and dysmenorrhea. Rofecoxib was approved in the US by the US Food and Drug Administration (FDA) in May 1999, and was marketed under the brand names Vioxx, Ceoxx, and Ceeoxx. Rofecoxib was available by prescription in both tablets and as an oral suspension.

<span class="mw-page-title-main">Celecoxib</span> Nonsteroidal anti-inflammatory drug

Celecoxib, sold under the brand name Celebrex among others, is a COX-2 inhibitor and nonsteroidal anti-inflammatory drug (NSAID). It is used to treat the pain and inflammation in osteoarthritis, acute pain in adults, rheumatoid arthritis, ankylosing spondylitis, painful menstruation, and juvenile rheumatoid arthritis. It may also be used to decrease the risk of colorectal adenomas in people with familial adenomatous polyposis. It is taken by mouth. Benefits are typically seen within an hour.

<span class="mw-page-title-main">Valdecoxib</span> Nonsteroidal anti-inflammatory drug

Valdecoxib is a nonsteroidal anti-inflammatory drug (NSAID) used in the treatment of osteoarthritis, rheumatoid arthritis, and painful menstruation and menstrual symptoms. It is a selective cyclooxygenase-2 inhibitor. It was patented in 1995.

COX-2 inhibitors (coxibs) are a type of nonsteroidal anti-inflammatory drug (NSAID) that directly target cyclooxygenase-2, COX-2, an enzyme responsible for inflammation and pain. Targeting selectivity for COX-2 reduces the risk of peptic ulceration and is the main feature of celecoxib, rofecoxib, and other members of this drug class.

<span class="mw-page-title-main">Etoricoxib</span> COX-2 selective NSAID medication

Etoricoxib, sold under the trade name Arcoxia, is a selective COX-2 inhibitor developed and commercialized by Merck. It is approved in 63 countries worldwide as of 2007, except the United States where the Food and Drug Administration sent a Non Approvable Letter to Merck and required them to provide additional data.

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<span class="mw-page-title-main">Meloxicam</span> Nonsteroidal anti-inflammatory drug (NSAID)

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COX-3 is an enzyme that is encoded by the PTGS1 (COX1) gene, but is not functional in humans. COX-3 is the third and most recently discovered cyclooxygenase (COX3050) isozyme, while the first two to be discovered were COX-1 and COX-2. The COX-3 isozyme is encoded by the same gene as COX-1, with the difference that COX-3 retains an intron that is not retained in COX-1.

<span class="mw-page-title-main">Etodolac</span> Nonsteroidal anti-inflammatory drug

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<span class="mw-page-title-main">Zomepirac</span> Withdrawn non-steroidal anti-inflammatory drug

Zomepirac is an orally effective nonsteroidal anti-inflammatory drug (NSAID) that has antipyretic actions. It was developed by McNeil Pharmaceutical, approved by the FDA in 1980, and sold as the sodium salt zomepirac sodium, under the brand name Zomax. Due to its clinical effectiveness, it was preferred by doctors in many situations and obtained a large share of the analgesics market; however, it was subsequently withdrawn in March 1983 due to its tendency to cause serious anaphylaxis in a small, but unpredictable, subset of the patient population.

Naproxcinod (nitronaproxen) is a nonsteroidal anti-inflammatory drug (NSAID) developed by the French pharmaceutical company NicOx. It is a derivative of naproxen with a nitroxybutyl ester to allow it to also act as a nitric oxide (NO) donor. This second mechanism of action makes naproxcinod the first in a new class of drugs, the cyclooxygenase inhibiting nitric oxide donators (CINODs), that are hoped to produce similar analgesic efficacy to traditional NSAIDs, but with less gastrointestinal and cardiovascular side effects.

Cyclooxygenases are enzymes that take part in a complex biosynthetic cascade that results in the conversion of polyunsaturated fatty acids to prostaglandins and thromboxane(s). Their main role is to catalyze the transformation of arachidonic acid into the intermediate prostaglandin H2, which is the precursor of a variety of prostanoids with diverse and potent biological actions. Cyclooxygenases have two main isoforms that are called COX-1 and COX-2. COX-1 is responsible for the synthesis of prostaglandin and thromboxane in many types of cells, including the gastro-intestinal tract and blood platelets. COX-2 plays a major role in prostaglandin biosynthesis in inflammatory cells and in the central nervous system. Prostaglandin synthesis in these sites is a key factor in the development of inflammation and hyperalgesia. COX-2 inhibitors have analgesic and anti-inflammatory activity by blocking the transformation of arachidonic acid into prostaglandin H2 selectively.

<span class="mw-page-title-main">Mavacoxib</span> Veterinary drug

Mavacoxib is a veterinary drug used to treat pain and inflammation in dogs with degenerative joint disease. It acts as a COX-2 inhibitor.

Ibuprofen/paracetamol, is a fixed-dose combination of two medications, ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), and paracetamol (acetaminophen). It is available as a generic medication and common brand names include Combiflam.

<span class="mw-page-title-main">Oliceridine</span> Opioid analgesic drug

Oliceridine, sold under the brand name Olinvyk, is an opioid medication that is used for the treatment of moderate to severe acute pain in adults. It is given by intravenous (IV) injection.

References

  1. Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  2. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 522. ISBN   9783527607495.
  3. Health "Association of Bextra (Valdecoxib) with Serious Adverse Drug Reactions". Health Canada. April 21, 2005.
  4. Gajraj NM (2007). "COX-2 inhibitors celecoxib and parecoxib: valuable options for postoperative pain management". Current Topics in Medicinal Chemistry. 7 (3): 235–49. doi:10.2174/156802607779941323. PMID   17305567.
  5. Kiehl S (March 13, 2005). "Secrecy on the Rise". The Baltimore Sun.
  6. Schug SA, Parsons B, Li C, Xia F (2017). "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 of Pain Research. 10: 2451–2459. doi: 10.2147/jpr.s136052 . PMC   5644539 . PMID   29066931.
  7. Langreth R (June 23, 2003). "The Chemical Cobbler". Forbes.
  8. "Dr. John Talley: 2001 St. Louis Awardee" (PDF). Chemical Bond. St. Louis Section, American Chemical Society. 52 (5): 2. May 2001. Archived from the original (PDF) on 15 April 2018.
  9. Mulita F, Karpetas G, Liolis E, Vailas M, Tchabashvili L, Maroulis I (February 2021). "Comparison of analgesic efficacy of acetaminophen monotherapy versus acetaminophen combinations with either pethidine or parecoxib in patients undergoing laparoscopic cholecystectomy: a randomized prospective study". Medicinski Glasnik. 18 (1): 27–32. doi:10.17392/1245-21. PMID   33155461.

Further reading