Valdecoxib is a

nonsteroidal anti-inflammatory drug Non-steroidal anti-inflammatory drugs (NSAID) are members of a Indication (medicine), therapeutic drug class which Analgesic, reduces pain, Anti-inflammatory, decreases inflammation, Antipyretic, decreases fever, and Antithrombotic, prevents bl ...

(NSAID) used in the treatment of

osteoarthritis Osteoarthritis is a type of degenerative joint disease that results from breakdown of articular cartilage, joint cartilage and underlying bone. A form of arthritis, it is believed to be the fourth leading cause of disability in the world, affect ...

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...

, and painful

menstruation Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and Mucous membrane, mucosal tissue from the endometrium, inner lining of the uterus through the vagina. The menstrual cycle is characterized ...

and menstrual symptoms. It is a selective cyclooxygenase-2 inhibitor. It was patented in 1995. 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 The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) on November 20, 2001, to treat arthritis and menstrual cramps, 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." In 2009, Bextra was at the center of the "largest health-care fraud settlement and the largest criminal fine of any kind ever." Pfizer paid a $2.3 billion civil and criminal fine.

Pharmacia & Upjohn 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 b ...

, a Pfizer subsidiary, violated the United States Food, Drug and Cosmetic Act for misbranding Bextra "with the intent to defraud or mislead." A water-soluble and injectable

prodrug A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be ...

of valdecoxib,

parecoxib Parecoxib, sold under the brand name Dynastat among others, is a water-soluble and injectable prodrug of valdecoxib. Parecoxib is a COX2 selective inhibitor. It is injectable. It is approved in the European Union for short term perioperative ...

, is marketed in the

European Union The European Union (EU) is a supranational union, supranational political union, political and economic union of Member state of the European Union, member states that are Geography of the European Union, located primarily in Europe. The u ...

under the tradename Dynastat.

Uses until 2005

In the United States, the FDA approved valdecoxib for the treatment of

, adult

, and primary

dysmenorrhea Dysmenorrhea, also known as period pain, painful periods or menstrual cramps, is pain during menstruation. Its usual onset occurs around the time that menstruation begins. Symptoms typically last less than three days. The pain is usually in th ...

. Valdecoxib was also used

off-label Off-label use is the use of pharmaceutical drugs for an unapproved indication (medicine), indication or in an unapproved age group, dose (biochemistry), dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) ca ...

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 A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...

and

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

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 Angina, also known as angina pectoris, is chest pain or pressure, usually caused by insufficient blood flow to the heart muscle (myocardium). It is most commonly a symptom of coronary artery disease. Angina is typically the result of parti ...

and

Stevens–Johnson syndrome Stevens–Johnson syndrome (SJS) is a type of severe skin reaction. Together with toxic epidermal necrolysis (TEN) and #Classification, Stevens–Johnson/toxic epidermal necrolysis (SJS/TEN) overlap, they are considered febrile mucocutaneous d ...

. Pfizer first acknowledged cardiovascular risks associated with Bextra in October 2004. The

American Heart Association The American Heart Association (AHA) is a nonprofit organization in the United States that funds cardiovascular medical research, educates consumers on healthy living and fosters appropriate Heart, cardiac care in an effort to reduce disability ...

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.

2009 settlement for off-label uses promotions

On September 2, 2009, the

United States Department of Justice The United States Department of Justice (DOJ), also known as the Justice Department, is a United States federal executive departments, federal executive department of the U.S. government that oversees the domestic enforcement of Law of the Unite ...

fined Pfizer $2.3 billion after one of its

subsidiaries A subsidiary, subsidiary company, or daughter company is a company completely or partially owned or controlled by another company, called the parent company or holding company, which has legal and financial control over the subsidiary company. Unl ...

, 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. 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 pleaded guilty to distribution of a misbranded product, and was fined $75,000 and 24 months on probation. The remaining $1 billion of the fine were paid to resolve allegations under the civil

False Claims Act False or falsehood may refer to: * False (logic), the negation of truth in classical logic * Lie or falsehood, a type of deception in the form of an untruthful statement * False statement, aka a falsehood, falsity, misstatement or untruth, is a st ...

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. Former Pfizer sales representative John Kopchinski acted as a

qui tam In common law, a writ of ''qui tam'' is a writ through which private citizen, private individuals who assist a prosecution can receive for themselves all or part of the damages or financial penalties recovered by the government as a result of the p ...

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.

Analytical methods

Several HPLC-UV methods have been reported for valdecoxib estimation in biological samples like human urine. Valdecoxib has analytical methods for bioequivalence studies, metabolite determination, estimation of formulation, and an HPTLC method for simultaneous estimation in tablet dosage form.

References

External links