Valdecoxib
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| Systematic (IUPAC) name | |
| 4-(5-methyl-3-phenylisoxazol-4-yl)benzenesulfonamide | |
| Clinical data | |
| Pregnancy cat. | C (AU) May cause premature closure of the ductus arteriosus |
| Legal status | Prescription Only (S4) (AU) Withdrawn in U.S., EU, Canada & parts of Asia |
| Routes | Oral |
| Pharmacokinetic data | |
| Bioavailability | 83% |
| Protein binding | 98% |
| Metabolism | Hepatic (CYP3A4 and 2C9 involved) |
| Half-life | 8 to 11 hours |
| Excretion | Renal |
| Identifiers | |
| CAS number | 181695-72-7  |
| ATC code | M01AH03 |
| PubChem | CID 119607 |
| DrugBank | DB00580 |
| ChemSpider | 106796  |
| UNII | 2919279Q3W |
| KEGG | D02709 |
| ChEBI | CHEBI:63634 |
| ChEMBL | CHEMBL865 |
| Chemical data | |
| Formula | C16H14N2O3S |
| Mol. mass | 314.364 g/mol |
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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. It was approved by the United States Food and Drug Administration on November 20, 2001,[1] and was available by prescription in tablet form until 2005, when it was removed from the market due to concerns about possible increased risk of heart attack and stroke.
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Uses until 2005 [edit]
In the United States, the Food and Drug Administration (FDA) approved valdecoxib for the treatment of osteoarthritis, adult rheumatoid arthritis, and primary dismennorhea.[2]
Valdecoxib was also used off-label for controlling acute pain and various types of surgical pain.[2]
Side-effects and withdrawal from market [edit]
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.
Recently in a large study published in JAMA 2006, valdecoxib appears less adverse for renal (kidney) disease and heart arrhythmia compared to Vioxx, however elevated renal risks were slightly suggested.[3]
2009 settlement for off-label uses promotions [edit]
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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."[4] 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.[5] A former Pfizer district sales manager was indicted and sentenced to home confinement for destroying documents regarding the illegal promotion of Bextra.[6][7] 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.[8]
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.[9] 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.[10] 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.[11]
Synthesis [edit]
Source:[12]
Assay of Valdecoxib[13] [edit]
Several HPLC-UV methods have been reported for valdecoxib estimation in biological samples like human urine,[14] plasma,.[15][16] Valdecoxib has analytical methods for bioequivalence studies,[17][18] metabolite determination,[19][20][21] and estimation of formulation,[22] HPTLC method for simultaneous estimation in tablet dosage form.[23]
See also [edit]
References [edit]
- ^ Thomson Micromedex. "Valdecoxib. U.S. FDA Drug Approval." Last accessed June 8, 2007.
- ^ a b "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. Retrieved 2012-07-04.
- ^ "Adverse Effects of Cyclooxygenase-2 Inhibitors on Renal and Arrhythmia Events: Meta-Analysis of Randomized Trials", (JAMA 2006, by Zhang JJ, Ding EL, Song Y.).
- ^ http://news.bbc.co.uk/2/hi/business/8234533.stm Pfizer agrees record fraud fine
- ^ http://www.usdoj.gov/usao/ma/Press%20Office%20-%20Press%20Release%20Files/Sept2009/PharmaciaPlea.html
- ^ http://www.usdoj.gov/usao/ma/Press%20Office%20-%20Press%20Release%20Files/Mar2009/FarinaconvictionPR.html
- ^ http://industry.bnet.com/pharma/10002882/pfizers-off-label-bextra-team-were-called-the-highlanders/
- ^ http://www.usdoj.gov/usao/ma/Press%20Office%20-%20Press%20Release%20Files/June2009/HollowayMarySentencingPR.html
- ^ http://www.fbi.gov/pressrel/pressrel09/justice_090209.htm
- ^ http://www.phillipsandcohen.com/CM/NewsSettlements/NewsSettlements536.asp
- ^ http://www.phillipsandcohen.com/CM/NewsSettlements/NewsSettlements531.asp
- ^ Talley, J. J.; Brown, D. L.; Carter, J. S.; Graneto, M. J.; Koboldt, C. M.; Masferrer, J. L.; Perkins, W. E.; Rogers, R. S. et al. (2000). "4-[5-Methyl-3-phenylisoxazol-4-yl]- benzenesulfonamide, Valdecoxib: A Potent and Selective Inhibitor of COX-2". Journal of Medicinal Chemistry 43 (5): 775. doi:10.1021/jm990577v. PMID 10715145.
- ^ Prafulla Kumar Sahu and M. Mathrusri Annapurna, Analytical method development by liquid chromatography, LAP Lambert Academic Publisher, Germany, 2011 ISBN 3-8443-2869-6.
- ^ Zhang J Y, Fast D M and Breau A P, J Chromatogr B Analyt Technol Biomed Life Sci., 2003, 785(1), 123-134
- ^ Ramakrishna N V S, Vishwottam K N; Wishu S and Koteshwara M, J Chromatogr B Analyt Technol Biomed Life Sci., 2004, 802(2), 271.
- ^ Sane R T, Menon S, Deshpande A Y and Jain A, Chromatogr., 2005, 61(3-4), 137-141.
- ^ 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.
- ^ 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.
- ^ Zhang J.Y, Fast D.M and Breau, A.P, J Pharm Biomed Anal., 2003, 33, 61.
- ^ Werner U, Werner D, Hinz B, Lanbrecht C and Brune K, J Biomed Chromatogr., 2004, 19, 113.
- ^ Zhang J V, Fast D M and Breau A P, J Chromatogr B Anal Technol Biomed Life Sci., 2003, 785, 123.
- ^ Sutariya V B, Rajashree M, Sankalia M G. and Priti P, Indian J Pharm Sci., 2004, 93, 112.
- ^ Gandhimathi M, Ravi T K, Shukla Nilima and Sowmiya G, Indian J Pharm Sci., 2007, 69(1), 145-147.
External links [edit]
- FDA Alert on Bextra withdrawal
- Large systematic review of adverse renal and arrhythmia risk of valdcoxib and other COX-2 inhibitors, JAMA 2006
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