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Clinical data | |
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Trade names | Bextra |
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Routes of administration | Oral |
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Pharmacokinetic data | |
Bioavailability | 83% |
Protein binding | 98% |
Metabolism | Hepatic (CYP3A4 and 2C9 involved) |
Elimination half-life | 8 to 11 hours |
Excretion | Renal |
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ChEBI | |
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CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.229.918 |
Chemical and physical data | |
Formula | C16H14N2O3S |
Molar mass | 314.36 g·mol−1 |
3D model (JSmol) | |
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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. [2]
Valdecoxib was manufactured and marketed under the brand name Bextra by G. D. Searle & Company as an anti-inflammatory arthritis drug. [3] It was approved by the United States Food and Drug Administration (FDA) on November 20, 2001, to treat arthritis and menstrual cramps. [4] [5] and was available by prescription in tablet form until 2005 when the FDA requested that Pfizer withdraw Bextra from the American market. [6] 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." [6]
In 2009, Bextra was at the center of the "largest health-care fraud settlement and the largest criminal fine of any kind ever." [4] [7] 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." [3]
A water-soluble and injectable prodrug of valdecoxib, parecoxib, is marketed in the European Union under the tradename Dynastat.
In the United States, the FDA approved valdecoxib for the treatment of osteoarthritis, adult rheumatoid arthritis, and primary dysmenorrhea. [8]
Valdecoxib was also used off-label for controlling acute pain and various types of surgical pain. [8]
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. [9]
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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, pleaded guilty to marketing four drugs, including Bextra, "with the intent to defraud or mislead." [10] 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. [11] A former Pfizer district sales manager was indicted and sentenced to home confinement for destroying documents regarding the illegal promotion of Bextra. [12] [13] In addition, a regional manager pleaded guilty to distribution of a misbranded product, and was fined $75,000 and 24 months on probation. [14]
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. [15] 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. [16] 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. [17]
Several HPLC-UV methods [18] have been reported for valdecoxib estimation in biological samples like human urine. [19] [20] Valdecoxib has analytical methods for bioequivalence studies, [21] [22] metabolite determination, [23] [24] [19] estimation of formulation, [25] and an HPTLC method for simultaneous estimation in tablet dosage form. [26]
Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of use, but largely include an increased risk of gastrointestinal ulcers and bleeds, heart attack, and kidney disease.
Pfizer Inc. is an American multinational pharmaceutical and biotechnology corporation headquartered at The Spiral in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer (1824–1906) and his cousin Charles F. Erhart (1821–1891).
Pharmacia was a pharmaceutical and biotechnological company in Sweden that merged with the American pharmaceutical company Upjohn in 1995.
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arteriosus in a premature baby. It can be used orally or intravenously. It typically begins working within an hour.
Rofecoxib is a COX-2-selective nonsteroidal anti-inflammatory drug (NSAID). It was marketed by Merck & Co. to treat osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, acute pain conditions, migraine, and dysmenorrhea. Rofecoxib was approved in the US by the US Food and Drug Administration (FDA) in May 1999, and was marketed under the brand names Vioxx, Ceoxx, and Ceeoxx. Rofecoxib was available by prescription in both tablets and as an oral suspension.
Celecoxib, sold under the brand name Celebrex among others, is a COX-2 inhibitor and nonsteroidal anti-inflammatory drug (NSAID). It is used to treat the pain and inflammation in osteoarthritis, acute pain in adults, rheumatoid arthritis, ankylosing spondylitis, painful menstruation, and juvenile rheumatoid arthritis. It may also be used to decrease the risk of colorectal adenomas in people with familial adenomatous polyposis. It is taken by mouth. Benefits are typically seen within an hour.
COX-2 inhibitors (coxibs) are a type of nonsteroidal anti-inflammatory drug (NSAID) that directly target cyclooxygenase-2, COX-2, an enzyme responsible for inflammation and pain. Targeting selectivity for COX-2 reduces the risk of peptic ulceration and is the main feature of celecoxib, rofecoxib, and other members of this drug class.
Pharmacia & Upjohn was a global pharmaceutical company formed by the merger of Sweden-based Pharmacia AB and the American company Upjohn in 1995. Today the remainder of the company is owned by Pfizer. In 1997, Pharmacia & Upjohn sold several brands to Johnson & Johnson, including Motrin and Cortaid.
G.D. Searle, LLC is a wholly owned subsidiary of Pfizer. It is currently a trademark company and subsidiary of Pfizer, operating in more than 43 countries. It also operates as a distribution trademark for various pharmaceuticals that were developed by G. D. Searle & Company. Searle is most notable for having developed the first female birth control pill, and the artificial sweetener NutraSweet. Searle also developed the drug Lomotil, an antidiarrheal medication. One of the notable Alumni of Searle is Donald Rumsfeld, the Secretary of Defense for George W. Bush in the 2000s. Prior to its 1985 merger with Monsanto, Searle was a company mainly focusing on life sciences, specifically pharmaceuticals, agriculture, and animal health.
Meloxicam, sold under the brand name Mobic among others, is a nonsteroidal anti-inflammatory medication (NSAID) used to treat pain and inflammation in rheumatic diseases and osteoarthritis. It is used by mouth or by injection into a vein. It is recommended that it be used for as short a period as possible and at a low dose.
Peter Rost is an American former drug marketing executive who is most known for taking public stances critical of the pharmaceutical industry as an "insider" and whistleblower. He sued his last two pharmaceutical employers, Wyeth and Pfizer, the latter of which fired him in 2005. At Wyeth, he uncovered tax evasion practices, and after informing senior company executives, was transferred from Sweden to a post in New Jersey. Rost sued the company, saying that the transfer was a retaliatory demotion, though the company said it was a promotion. Rost settled with Wyeth for an undisclosed amount in 2003. At Pfizer, Rost filed a qui tam suit disclosing off-label marketing of Genotropin at Pharmacia prior to its purchase by Pfizer. The U.S. Department of Justice declined to join in Rost's suit as the marketing violations had already been disclosed to the Department by Pfizer. Rost was eventually fired by Pfizer, and sued for wrongful dismissal, but this lawsuit was summarily dismissed by the court based on evidence that Pfizer had decided to fire Rost prior to discovery of his whistleblowing activities. Since then, Rost has worked outside the pharmaceutical industry, as a public speaker, blogger, writer, and litigation consultant.
Fenoprofen, sold under the brand name Nalfon among others, is a nonsteroidal anti-inflammatory drug (NSAID). Fenoprofen calcium is used for symptomatic relief for rheumatoid arthritis, osteoarthritis, and mild to moderate pain. It has also been used to treat postoperative pain. It is available as a generic medication.
The ethics involved within pharmaceutical sales is built from the organizational ethics, which is a matter of system compliance, accountability and culture. Organizational ethics are used when developing the marketing and sales strategy to both the public and the healthcare profession of the strategy. Organizational ethics are best demonstrated through acts of fairness, compassion, integrity, honor, and responsibility.
Cyclooxygenases are enzymes that take part in a complex biosynthetic cascade that results in the conversion of polyunsaturated fatty acids to prostaglandins and thromboxane(s). Their main role is to catalyze the transformation of arachidonic acid into the intermediate prostaglandin H2, which is the precursor of a variety of prostanoids with diverse and potent biological actions. Cyclooxygenases have two main isoforms that are called COX-1 and COX-2. COX-1 is responsible for the synthesis of prostaglandin and thromboxane in many types of cells, including the gastro-intestinal tract and blood platelets. COX-2 plays a major role in prostaglandin biosynthesis in inflammatory cells and in the central nervous system. Prostaglandin synthesis in these sites is a key factor in the development of inflammation and hyperalgesia. COX-2 inhibitors have analgesic and anti-inflammatory activity by blocking the transformation of arachidonic acid into prostaglandin H2 selectively.
Wyeth was a pharmaceutical company until it was purchased by Pfizer in 2009. The company was founded in Philadelphia, Pennsylvania, in 1860 as John Wyeth and Brother. Its headquarters moved to Collegeville, Pennsylvania, and Madison, New Jersey, before its headquarters were consolidated with Pfizer's in New York City after the 2009 merger.
Stefan Philip Kruszewski is an American clinical and forensic psychiatrist, active as a whistleblower in medically related cases. He is principal in the company which bears his name, Stefan P. Kruszewski, M.D. & Associates, P.C. in Harrisburg, Pennsylvania.
Pharmaceutical fraud involves activities that result in false claims to insurers or programs such as Medicare in the United States or equivalent state programs for financial gain to a pharmaceutical company. There are several different schemes used to defraud the health care system which are particular to the pharmaceutical industry. These include: Good Manufacturing Practice (GMP) Violations, Off Label Marketing, Best Price Fraud, CME Fraud, Medicaid Price Reporting, and Manufactured Compound Drugs. Examples of fraud cases include the GlaxoSmithKline $3 billion settlement, Pfizer $2.3 billion settlement, and Merck $650 million settlement. Damages from fraud can be recovered by use of the False Claims Act, most commonly under the qui tam provisions which rewards an individual for being a "whistleblower", or relator (law).
Marketing of off-label use is advertising the use of drugs for purposes not approved by the regional government. The practice is often illegal and has led to most of the largest pharmaceutical settlements after Franklin v. Parke-Davis, in which a court ruled off-label marketing a violation of the False Claims Act.