Bextra

Bextra, a COX-2 inhibitor used in the treatment of arthritis, contains an isoxazole ring. Why is the ring aromatic ... 

Michael reactions and, 895 Beta-keto ester, 851 alkylation of, 859-860 cyclic, 892-893 decarboxylation of, 857, 860 Michael reactions and. 895 pKd of, 852 synthesis of, 892-893 Beta-lactam antibiotics, 824-825 Beta oxidation pathway, 1133-1137 mechanism of, 1133-1136 Beta-pleated sheet (protein), 1038 molecular model of, 1039 secondary protein structure and, 1038-1039 Betaine, 720 Bextra. structure of, 544 BHA, synthesis of, 629 BHT, synthesis of. 629 Bicycloalkane. 129 Bijvoet. J. M., 299 Bimolecular, 363... 

Aleatory uncertainty —the roll of the die—describes risks that cannot practicably be predicted within the research process, for example, new failure modes, or modes that can only be detected in late stages of work, for example, humans. An example of aleatory uncertainty is the withdrawal in the UK of Bextra on the basis of two serious adverse events out of 40,000 patients this could only be discovered after launch [2]. This, without hindsight, was an uncontrollable risk. ... 

Valdecoxib Bextra Pfizer, Inc. Cox-2 inhibitor 11/1/2002 4/7/2005 2.5 years Serious and potentially life-threatening skin reactions (Unavailable)... 

Valdecoxib (Bextra Pfizer), a second COX-2 specific inhibitor NSAID was taken off the market a few months after Vioxx. In addition to a higher risk of serious skin toxicity, pahents given Vioxx after Coronary Bypass Surgery had a higher rate of myocardial infarchons. 

In the aftermath of the Vioxx and Bextra withdrawals, the FDA studied the CV and GI risks in great detail. A very recent request for strengthening the warnings and precautions on all NSAID products was released, and reads as follows ... 

Refer to Section 6.3 to describe the phases of a clinical trial. Phase IV trials are necessary to maintain a close watch on the efficacy and adverse events of an approved drug when it is administered to the population at large. For example, even a small percentage of adverse events in Phase III trial for several thousand people may translate into a substantial number when a drug is made available to milhons of people. A case in point is Vioxx and Bextra (see Section 2.9). 

Durazanil, Lectopam, Lexotan Auxit, Bisolvon, Ophthosol Parlodel, Pravidel, Serono-Bagren Lendorm (A), Lendormin Bextra... 

U.S. Food and Drug Administration. Information for Healthcare Professionals Valdecoxib (Marketed as Bextra). http // www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafety InformationforPatientsandProviders/ucml24649.htm (accessed February 2011). 

Drugs specifically designed for COX-2 selectivity have been marketed quite successfully, especially in the United States. The drugs that were part of this litigation were celecoxib (Celebrex ) and valdecoxib (Bextra ). COX-2 selective inhibitors have been shrouded in controversy since their use has been in some cases linked with increased risk of heart attacks and stroke. Celebrex and Bextra were both marketed by Pfizer, but Bextra was pulled from the United States market in 2005 out of safety concerns. The COX-2 selective inhibitor rofecoxib (Vioxx ) was marketed by Merck and was voluntarily pulled from the market by Merck in 2004. Celebrex remains on the market, and worldwide sales in 2007 were over 2 billion. 

The 850 patent described the COX-1 and COX-2 enzymes as well as assays useful for distinguishing whether a compound was a selective inhibitor for the COX-2 enzyme. The 850 patent also described methods of using COX-2 selective compounds as well as their formulation, routes of administration, possible effective doses, and suitable dosage forms. On the day that the 850 patent issued, the University of Rochester sued Pfizer, G. D. Searle, and related parties in a federal district court alleging that Pfizer s marketing of Celebrex and Bextra infringed several claims of the patent (including claim l).22... 

Both Celebrex and Bextra were developed by Searle, which was subsequently purchased by Monsanto. Monsanto later merged with Pharmacia and Upjohn, and the resultant company later merged with Pfizer. 23 University of Rochester v. G.D. Searle Co., 249 F.2d 216 (W.D. N.Y. 2003). The District Court also held the claims to be invalid due to lack of enablement, an issue we will discuss further later in this chapter. 

The diaryl pyrazole derivative celecoxib (Celebrex /Pharmacia, Pfizer), the fiiranone derivative rofecoxib (Vioxx /Merck), and the isoxazole derivative valdecoxib (Bextra /... 

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