Valdecoxib

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Valdecoxib
Valdecoxib.svg
Valdecoxib3DanJ.gif
Systematic (IUPAC) name
4-(5-methyl-3-phenylisoxazol-4-yl)benzenesulfonamide
Clinical data
Trade names Bextra
Pregnancy
category
  • AU: C
Legal status
Routes of
administration		 Oral
Pharmacokinetic data
Bioavailability 83%
Protein binding 98%
Metabolism Hepatic (CYP3A4 and 2C9 involved)
Biological half-life 8 to 11 hours
Excretion Renal
Identifiers
CAS Number 181695-72-7 N
ATC code M01AH03 (WHO)
PubChem CID: 119607
IUPHAR/BPS 2894
DrugBank DB00580 YesY
ChemSpider 106796 YesY
UNII 2919279Q3W YesY
KEGG D02709 YesY
ChEBI CHEBI:63634 N
ChEMBL CHEMBL865 YesY
Chemical data
Formula C16H14N2O3S
Molecular mass 314.364 g/mol
  • O=S(=O)(N)c3ccc(c2c(onc2c1ccccc1)C)cc3
  • InChI=1S/C16H14N2O3S/c1-11-15(12-7-9-14(10-8-12)22(17,19)20)16(18-21-11)13-5-3-2-4-6-13/h2-10H,1H3,(H2,17,19,20) YesY
  • Key:LNPDTQAFDNKSHK-UHFFFAOYSA-N YesY
 NYesY (what is this?)  (verify)

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

Valdecoxib was manufactured and marketed under the brand name Bextra by G. D. Searle & Company as an anti-inflammatory arthritis drug.[1] It was approved by the United States Food and Drug Administration on November 20, 2001, to treat arthritis and menstrual cramps.[2][3] and was available by prescription in tablet form until 2005 when the FDA requested that Pfizer withdraw Bextra from the American market.[4] The FDA cited "potential increased risk for serious cardiovascular (CV) adverse events," an "increased risk of serious skin reactions" and the "fact that Bextra has not been shown to offer any unique advantages over the other available NSAIDs."[4]

In September 2009 Bextra was at the center of the "largest health care fraud settlement and the largest criminal fine of any kind ever."[2][5] Pfizer paid a $2.3 billion civil and criminal fine. Pharmacia and Upjohn, a Pfizer subsidiary, violated the United States Food, Drug and Cosmetic Act for misbranding Bextra "with the intent to defraud or mislead."[1]

A water-soluble and injectable prodrug of valdecoxib, parecoxib is marketed in the European Union under the tradename Dynastat.

Uses until 2005

In the United States, the Food and Drug Administration (FDA) approved valdecoxib for the treatment of osteoarthritis, adult rheumatoid arthritis, and primary dysmenorrhea.[6]

Valdecoxib was also used off-label for controlling acute pain and various types of surgical pain.[6]

Side-effects and withdrawal from market

On April 7, 2005, Pfizer withdrew Bextra from the U.S. market on recommendation by the FDA, citing an increased risk of heart attack and stroke and also the risk of a serious, sometimes fatal, skin reaction. This was a result of recent attention to prescription NSAIDs, such as Merck's Vioxx. Other reported side-effects were angina and Stevens–Johnson syndrome.

Pfizer first acknowledged cardiovascular risks associated with Bextra in October 2004. The American Heart Association soon after was presented with a report indicating patients using Bextra while recovering from heart surgery were 2.19 times more likely to suffer a stroke or heart attack than those taking placebos.

In a large study published in the The Journal of the American Medical Association in 2006, valdecoxib appeared less adverse for renal (kidney) disease and heart arrhythmia compared to Vioxx, however elevated renal risks were slightly suggested.[7]

2009 settlement for off-label uses promotions

Lua error in package.lua at line 80: module 'strict' not found. On September 2, 2009, the United States Department of Justice fined Pfizer $2.3 billion after one of its subsidiaries, Pharmacia & UpJohn Company, pled guilty to marketing four drugs including Bextra "with the intent to defraud or mislead."[8] Pharmacia & UpJohn admitted to criminal conduct in the promotion of Bextra, and agreed to pay the largest criminal fine ever imposed in the United States for any matter, $1.195 billion.[9] A former Pfizer district sales manager was indicted and sentenced to home confinement for destroying documents regarding the illegal promotion of Bextra.[10][11] In addition, a Regional Manager pled guilty to distribution of a mis-branded product, and was fined $75,000 and twenty-four months on probation.[12]

The remaining $1 billion of the fine was paid to resolve allegations under the civil False Claims Act case and is the largest civil fraud settlement against a pharmaceutical company. Six whistle-blowers were awarded more than $102 million for their role in the investigation.[13] Former Pfizer sales representative John Kopchinski acted as a qui tam relator and filed a complaint in 2004 outlining the illegal conduct in the marketing of Bextra.[14] Kopchinski was awarded $51.5 million for his role in the case because the improper marketing of Bextra was the largest piece of the settlement at $1.8 billion.[15]

Assay of Valdecoxib[16]

Several HPLC-UV methods have been reported for valdecoxib estimation in biological samples like human urine,[17] plasma,.[18][19] Valdecoxib has analytical methods for bioequivalence studies,[20][21] metabolite determination,[22][23][24] and estimation of formulation,[25] HPTLC method for simultaneous estimation in tablet dosage form.[26]

See also

References

  1. ↑ 1.0 1.1 Lua error in package.lua at line 80: module 'strict' not found.
  2. ↑ 2.0 2.1 Lua error in package.lua at line 80: module 'strict' not found.
  3. ↑ Thomson Micromedex. "Valdecoxib. U.S. FDA Drug Approval." Last accessed June 8, 2007.
  4. ↑ 4.0 4.1 Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ 6.0 6.1 Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  9. ↑ http://www.usdoj.gov/usao/ma/Press%20Office%20-%20Press%20Release%20Files/Sept2009/PharmaciaPlea.html
  10. ↑ http://www.usdoj.gov/usao/ma/Press%20Office%20-%20Press%20Release%20Files/Mar2009/FarinaconvictionPR.html
  11. ↑ http://industry.bnet.com/pharma/10002882/pfizers-off-label-bextra-team-were-called-the-highlanders/
  12. ↑ http://www.usdoj.gov/usao/ma/Press%20Office%20-%20Press%20Release%20Files/June2009/HollowayMarySentencingPR.html
  13. ↑ http://www.fbi.gov/pressrel/pressrel09/justice_090209.htm
  14. ↑ http://www.phillipsandcohen.com/CM/NewsSettlements/NewsSettlements536.asp
  15. ↑ http://www.phillipsandcohen.com/CM/NewsSettlements/NewsSettlements531.asp
  16. ↑ Prafulla Kumar Sahu and M. Mathrusri Annapurna, Analytical method development by liquid chromatography, LAP Lambert Academic Publisher, Germany, 2011 ISBN 3-8443-2869-6.
  17. ↑ Zhang J Y, Fast D M and Breau A P, J Chromatogr B Analyt Technol Biomed Life Sci., 2003, 785(1), 123-134
  18. ↑ Ramakrishna N V S, Vishwottam K N; Wishu S and Koteshwara M, J Chromatogr B Analyt Technol Biomed Life Sci., 2004, 802(2), 271.
  19. ↑ Sane R T, Menon S, Deshpande A Y and Jain A, Chromatogr., 2005, 61(3-4), 137-141.
  20. ↑ Prafulla Kumar Sahu*, K. Ravi Sankar and M. Mathrusri Annapurna, Determination of Valdecoxib in human plasma using Reverse Phase HPLC”, E-Journal of Chemistry, 2011, 8(2), 875-881.
  21. ↑ Mandal U, Jayakumar M, Ganesan M, Nandi S, Pal T K, Chakraborty M K, Roy Chowdhary A. and Chattoraj T K, Indian Drugs, 2004, 41, 59.
  22. ↑ Zhang J.Y, Fast D.M and Breau, A.P, J Pharm Biomed Anal., 2003, 33, 61.
  23. ↑ Werner U, Werner D, Hinz B, Lanbrecht C and Brune K, J Biomed Chromatogr., 2004, 19, 113.
  24. ↑ Zhang J V, Fast D M and Breau A P, J Chromatogr B Anal Technol Biomed Life Sci., 2003, 785, 123.
  25. ↑ Sutariya V B, Rajashree M, Sankalia M G. and Priti P, Indian J Pharm Sci., 2004, 93, 112.
  26. ↑ Gandhimathi M, Ravi T K, Shukla Nilima and Sowmiya G, Indian J Pharm Sci., 2007, 69(1), 145-147.

External links

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