Valdecoxib

Valdecoxib

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Systematic (IUPAC) name
4-(5-methyl-3-phenylisoxazol-4-yl)benzenesulfonamide
Clinical data
Pregnancy category	AU: C May cause premature closure of the ductus arteriosus
Routes of administration	Oral
Legal status
Legal status	Withdrawn in U.S., EU, Canada & parts of Asia
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
ATC code	M01AH03 (WHO)
PubChem	CID 119607
DrugBank	APRD00183
Chemical data
Formula	C16H14N2O3S
Molar mass	314.364 g/mol[[]]

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, 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.

Uses

Since its registration, Bextra was prescribed for pain associated with arthritis, menstrual discomfort, and other ailments.

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.

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.

Off-label settlement

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." 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. A former Pfizer district sales manager was indicted and sentenced to home confinement for destroying documents regarding the illegal promotion of Bextra. 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.

The remaining $1 billion dollars 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. 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. 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.

Synthesis

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Source:

See also

• Discovery and development of cyclooxygenase 2 inhibitors

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

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