Valdecoxib
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|
| Systematic (IUPAC) name |
| 4-(5-methyl-3-phenylisoxazol-4-yl)benzenesulfonamide |
| Clinical data |
| Trade names |
Bextra |
| 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Prescription Only (S4) (AU) Withdrawn in U.S., EU, Canada & parts of Asia |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 N |
| ATC code |
M01AH03 |
| PubChem |
CID 119607 |
| DrugBank |
DB00580 |
| ChemSpider |
106796 Y |
| UNII |
2919279Q3W Y |
| KEGG |
D02709 Y |
| ChEBI |
CHEBI:63634 N |
| ChEMBL |
CHEMBL865 Y |
| Chemical data |
| Formula |
C16H14N2O3S |
| Mol. mass |
314.364 g/mol |
SMILES
- O=S(=O)(N)c3ccc(c2c(onc2c1ccccc1)C)cc3
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InChI
-
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) Y
Key:LNPDTQAFDNKSHK-UHFFFAOYSA-N Y
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| N (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. 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. The prodrug parecoxib is available in many countries.
Contents
- 1 Uses until 2005
- 2 Side-effects and withdrawal from market
- 3 2009 settlement for off-label uses promotions
- 4 Synthesis
- 5 Assay of Valdecoxib[13]
- 6 See also
- 7 References
- 8 External links
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.[2]
Valdecoxib was also used off-label for controlling acute pain and various types of surgical pain.[2]
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 JAMA 2006, valdecoxib appeared 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
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An editor has expressed a concern that this section lends undue weight to certain ideas relative to the article as a whole. Please help to discuss and resolve the dispute before removing this message. (December 2012) |
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
Source:[12]
Assay of Valdecoxib[13]
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
- Discovery and development of cyclooxygenase 2 inhibitors
- Parecoxib
- Apricoxib
References
- ^ 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.; Shaffer, A. F.; Zhang, Y. Y.; Zweifel, B. S.; Seibert, K. (2000). "4-[5-Methyl-3-phenylisoxazol-4-yl]- benzenesulfonamide, Valdecoxib: A Potent and Selective Inhibitor of COX-2". Journal of Medicinal Chemistry 43 (5): 775–777. doi:10.1021/jm990577v. PMID 10715145. edit
- ^ 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
- FDA Alert on Bextra withdrawal
- Large systematic review of adverse renal and arrhythmia risk of valdcoxib and other COX-2 inhibitors, JAMA 2006
