Valdecoxib Explained

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.[1]

Valdecoxib was manufactured and marketed under the brand name Bextra by G. D. Searle & Company as an anti-inflammatory arthritis drug. It was approved by the United States Food and Drug Administration (FDA) on November 20, 2001, to treat arthritis and menstrual cramps.[2] and was available by prescription in tablet form until 2005 when the FDA requested that Pfizer withdraw Bextra from the American market. 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."[3]

In 2009, Bextra was at the center of the "largest health-care fraud settlement and the largest criminal fine of any kind ever."[4] [5] Pfizer paid a $2.3 billion civil and criminal fine. Pharmacia & Upjohn, a Pfizer subsidiary, violated the United States Food, Drug and Cosmetic Act for misbranding Bextra "with the intent to defraud or mislead."[6]

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 FDA approved valdecoxib for the treatment of osteoarthritis, adult rheumatoid arthritis, and primary dysmenorrhea.[7]

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

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 Journal of the American Medical Association in 2006, valdecoxib appeared less adverse for renal (kidney) disease and heart arrhythmia compared to Vioxx, but elevated renal risks were slightly suggested.[8]

2009 settlement for off-label uses promotions

On September 2, 2009, the United States Department of Justice fined Pfizer $2.3 billion after one of its subsidiaries, Pharmacia & Upjohn Company, pleaded guilty to marketing four drugs, including Bextra, "with the intent to defraud or mislead." 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 pleaded guilty to distribution of a misbranded product, and was fined $75,000 and 24 months on probation.[12]

The remaining $1 billion of the fine were paid to resolve allegations under the civil False Claims Act case and is the largest civil fraud settlement against a pharmaceutical company. Six whistleblowers 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]

Analytical methods

Several HPLC-UV methods[16] have been reported for valdecoxib estimation in biological samples like human urine.[17] [18] Valdecoxib has analytical methods for bioequivalence studies,[19] [20] metabolite determination,[21] [22] estimation of formulation,[23] and an HPTLC method for simultaneous estimation in tablet dosage form.[24]

See also

External links

Notes and References

  1. Book: Fischer J, Ganellin CR . Analogue-based Drug Discovery . 2006 . John Wiley & Sons . 9783527607495 . 52X . en.
  2. Web site: Thomson Micromedex . Valdecoxib. U.S. FDA Drug Approval . June 8, 2007 .
  3. Web site: Information for Healthcare Professionals: Valdecoxib (marketed as Bextra) . U.S. Food and Drug Administration . 2005 . 28 December 2015.
  4. News: Pfizer Pays $2.3 Billion to Settle Marketing Case . New York Times . 2 September 2009 . 28 December 2015 . Gardiner H .
  5. Web site: Inside Pfizer's palace coup . Fortune . 28 July 2011 . 28 December 2015 . Elkind P, Reingold J .
  6. Web site: Pfizer fined $2.3B in record fraud settlement Pharma giant illegally promoted product: Justice Department says, in largest health care fraud settlement in history . CNN . 2 September 2009 . 28 December 2015 . Washington.
  7. Web site: Pfizer to pay $2.3 billion to resolve criminal and civil health care liability relating to fraudulent marketing and the payment of kickbacks . Stop Medicare Fraud, US Dept of Health & Human Svc, and of Justice . 2012-07-04 . https://web.archive.org/web/20120830023954/http://www.stopmedicarefraud.gov/pfizerfactsheet.html . 2012-08-30 .
  8. Zhang J, Ding EL, Song Y . Adverse effects of cyclooxygenase 2 inhibitors on renal and arrhythmia events: meta-analysis of randomized trials . JAMA . 296 . 13 . 1619–1632 . October 2006 . 16968832 . 10.1001/jama.296.13.jrv60015 . 2006-09-17 . dead . https://web.archive.org/web/20201105042613/http://www.cox2drugreview.org/ . 2020-11-05 .
  9. Web site: Pharmacia & Upjohn Company Inc Pleads Guilty to Fraudulent Marketing of Bextra . The United States Attorney's Office, District of Massachusetts . 2009-10-16 . https://archive.today/20091207084948/http://www.usdoj.gov/usao/ma/Press%20Office%20-%20Press%20Release%20Files/Sept2009/PharmaciaPlea.html . 15 September 2009 . 7 December 2009 . dead .
  10. Web site: Ex-Pfizer Manager Found Guilty of Obstruction . 17 March 2009 . The United States Department of Justice - United States Attorney's Office - District of Massachusetts . 16 October 2009 . 1 June 2009 . https://web.archive.org/web/20090601004701/http://www.usdoj.gov/usao/ma/Press%20Office%20-%20Press%20Release%20Files/Mar2009/FarinaconvictionPR.html . dead .
  11. Web site: Edwards J . Pfizer's Off-Label Bextra Team Was Called "The Highlanders" - CBS News . https://web.archive.org/web/20090629192750/http://industry.bnet.com/pharma/10002882/pfizers-off-label-bextra-team-were-called-the-highlanders/ . dead . June 29, 2009 . Industry.bnet.com . 2009-06-26 . 2019-06-06.
  12. Web site: Pharmaceutical Company Manager Sentenced for Off-Label Marketing . The United States Department of Justice - United States Attorney's Office - District of Massachusetts . 18 June 2009 . 16 October 2009 . 1 September 2009. https://web.archive.org/web/20090901044434/http://www.usdoj.gov/usao/ma/Press%20Office%20-%20Press%20Release%20Files/June2009/HollowayMarySentencingPR.html . dead .
  13. Web site: Justice Department Announces Largest Health Care Fraud Settlement in Its History: Pfizer to Pay $2.3 Billion for Fraudulent Marketing . Federal Bureau of Investigation - Press Release . 2 September 2009 . 28 July 2016 . 9 September 2010 . https://web.archive.org/web/20100909224747/http://www.fbi.gov/pressrel/pressrel09/justice_090209.htm . dead .
  14. Web site: Pfizer settlement and Bextra whistleblower case: News stories and court documents. https://web.archive.org/web/20110205035652/http://www.phillipsandcohen.com/CM/NewsSettlements/NewsSettlements536.asp . 5 February 2011 . Whistleblower News | Articles, Blogs, & Insights . Phillips & Cohen LLP . 6 June 2019 .
  15. Web site: Bextra whistleblower case leads to record-setting Pfizer settlement . https://web.archive.org/web/20101229034918/http://www.phillipsandcohen.com/CM/NewsSettlements/NewsSettlements531.asp . 29 December 2010 . Whistleblower news . Phillips & Cohen LLP . 2019-06-06.
  16. Book: Sahu PK, Annapurna MM . Analytical method development by liquid chromatography . LAP Lambert Academic Publisher . Germany . 2011 . 978-3-8443-2869-1 .
  17. Zhang JY, Fast DM, Breau AP . Determination of valdecoxib and its metabolites in human urine by automated solid-phase extraction-liquid chromatography-tandem mass spectrometry . Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences . 785 . 1 . 123–134 . February 2003 . 12535845 . 10.1016/s1570-0232(02)00863-2 .
  18. Sane RT, Menon S, Deshpande AY, Jain A . HPLC determination and pharmacokinetic study of valdecoxib in human plasma. . Chromatographia . February 2005 . 61 . 3–4 . 137–41 . 10.1365/s10337-004-0442-2 . 95275785 .
  19. Sahu PK, Sankar KR, Annapurna MM . Determination of Valdecoxib in Human Plasma Using Reverse Phase HPLC. . Journal of Chemistry . 2011 . 8 . 2 . 875–881 .
  20. Mandal U, Jayakumar M, Ganesan M, Nandi S, Pal TK, Chakraborty MK, Roy Chowdhary A, Chattoraj TK . [title] . Indian Drugs . 2004 . 41 . 59 .
  21. Zhang JY, Fast DM, Breau AP . Development and validation of an automated SPE-LC-MS/MS assay for valdecoxib and its hydroxylated metabolite in human plasma . Journal of Pharmaceutical and Biomedical Analysis . 33 . 1 . 61–72 . September 2003 . 12946532 . 10.1016/s0731-7085(03)00349-2 .
  22. Werner U, Werner D, Hinz B, Lambrecht C, Brune K . A liquid chromatography-mass spectrometry method for the quantification of both etoricoxib and valdecoxib in human plasma . Biomedical Chromatography . 19 . 2 . 113–118 . March 2005 . 15473012 . 10.1002/bmc.423 .
  23. Sutariya VB, Rajashree M, Sankalia MG, Priti P . Spectrophotometric Estimation Of Valdecoxib In Pure Form And Tablets . Indian Journal of Pharmaceutical Sciences . 2004 . 66 . 3 . 360–362 .
  24. Gandhimathi M, Ravi TK, Shukla N, Sowmiya G . High Performance Thin Layer Chromatographic Method for Simultaneous Estimation of Paracetamol and Valdecoxib in Tablet Dosage Form. . Indian Journal of Pharmaceutical Sciences . January 2007 . 69 . 1 . 145 . 10.4103/0250-474X.32133 . free .

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