Valdecoxib is a nonsteroidal anti-inflammatory drug (NSAID) used in the treatment of

osteoarthritis Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the w ...

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

, and painful menstruation 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 respon ...

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 bra ...

, a Pfizer subsidiary, violated the United States

Food, Drug and Cosmetic Act The United States Federal Food, Drug, and Cosmetic Act (abbreviated as FFDCA, FDCA, or FD&C) is a set of laws passed by the United States Congress in 1938 giving authority to the U.S. Food and Drug Administration (FDA) to oversee the safety of f ...

for misbranding Bextra "with the intent to defraud or mislead." A water-soluble and injectable prodrug 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 through much of Europe for short term perioperative ...

is marketed in the

European Union The European Union (EU) is a supranational political and economic union of member states that are located primarily in Europe. The union has a total area of and an estimated total population of about 447million. The EU has often been de ...

under the tradename Dynastat.

Uses until 2005

In the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territori ...

, the

(FDA) approved valdecoxib for the treatment of

, adult

, and primary dysmenorrhea. Valdecoxib was also used

off-label Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although ...

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 blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which ma ...

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 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 ...

. Other reported side-effects were angina and

Stevens–Johnson syndrome Stevens–Johnson syndrome (SJS) is a type of severe skin reaction. Together with toxic epidermal necrolysis (TEN) and Stevens–Johnson/toxic epidermal necrolysis (SJS/TEN), it forms a spectrum of disease, with SJS being less severe. Erythema ...

. 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 A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. In general, placebos can af ...

. 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, however 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 federal executive department of the United States government tasked with the enforcement of federal law and administration of justice in the United Stat ...

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." 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 An indictment ( ) is a formal accusation that a person has committed a crime. In jurisdictions that use the concept of felonies, the most serious criminal offence is a felony; jurisdictions that do not use the felonies concept often use that of ...

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 mis-branded product, and was fined $75,000 and twenty-four months on probation. The remaining $1 billion of the fine was paid to resolve allegations under the civil

False Claims Act The False Claims Act (FCA), also called the "Lincoln Law", is an American federal law that imposes liability on persons and companies (typically federal contractors) who defraud governmental programs. It is the federal government's primary litigat ...

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 In common law, a writ of ''qui tam'' is a writ through which 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 prosecution. Its ...

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.

Assay of valdecoxib

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