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Lovenox

In medicine, low molecular weight heparin (LMWH) is a class of medication used as an anticoagulant in diseases that feature thrombosis, as well as for prophylaxis in situations that lead to a high risk of thrombosis. more...

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Heparin is a naturally-occurring polysaccharide that inhibits coagulation, the process whereby thrombosis occurs. In nature, heparin consists of molecular chains of varying lengths, or molecular weights. Heparin derived from natural sources (including intestine) can be administered therapeutically to prevent thrombosis (see anticoagulation). However, the effects of natural, or unfractionated, heparin can be difficult to predict. After a standard dose of unfractionated heparin, coagulation parameters must be monitored very closely to prevent over- or under-anticoagulation.

Low molecular weight heparin, in contrast, consists of only short chains of polysaccharide, obtained by the deaminative hydrolysis of unfractionated heparin. Nitrous acid selectively cleaves the glycosidic bonds of the heparin with formation of di, tetra, hexa and higher saccharides terminated with 2,5-anhydro-D-mannose (AM) residues as reducing terminal groups. Having a lower average molecular weight means that a given dose of LMWH will be absorbed more predictably, leading to overall more predictable anticoagulation. It is also more selective for factor Xa and has less effect on thrombin.

Its differences with unfractioned heparin are:

  • Average molecular weight: heparin is about 20000 Da and LMWH is about 3000 Da
  • No need for monitoring of the APTT coagulation parameter
  • Possibly a smaller risk of bleeding
  • Smaller risk of osteoporosis in long-time use
  • Smaller risk of heparin-induced thrombocytopenia, a feared side-effect of heparin.

Because it can be given subcutaneously and does not require aPTT monitoring, LMWH permits outpatient treatment of conditions such as deep vein thrombosis or pulmonary embolism that previously mandated inpatient hospitalization for unfractionated heparin administration

The use of LMWH needs to be monitored closely in patients at extremes of weight or in patients with renal dysfunction. An anti-factor Xa activity may be useful for monitoring anticoagulation. Given its renal clearance, LMWH may not be feasible in patients who have end stage renal disease.

Makes of LMWHs include:

  • Bemiparin (Zibor®)
  • Dalteparin (Fragmin®)
  • Enoxaparin (Clexane® and Lovenox®)
  • Nadroparin (Fraxiparin® and Fraxodi®)
  • Tinzaparin (Innohep®)
  • Several others

Reference

  • Weitz JI. Low-molecular-weight heparins. N Engl J Med 1997;337:688-98. PMID 9278467.

Read more at Wikipedia.org


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Protect, defend … and keep moving ahead
From Food & Drug Packaging, 7/1/05 by Lisa McTigue Pierce

The August 2004 merger of French pharmaceutical giants Sanofi-Synthelabo and Aventis created the third largest pharmaceutical company in the world: sanofi-aventis.

Don't let the lowercase treatment fool you, sanofi-aventis is not a quiet company abroad. It ranks No. 1 in Europe. And, with the Aventis merger, it's poised to make noise in the U.S. The company conducts its business here through its subsidiaries Sanofi Synthelabo Inc., Aventis Pharmaceuticals Inc. and Sanofi Pasteur Inc. sanofi-aventis concentrates on drug development in seven areas: cardiovascular, thrombosis, oncology, metabolic diseases, central nervous system, internal medicine and vaccines. The last business got a boost from strong U.S. sales in late 2004 when rival Chiron failed to deliver enough flu shots. Fourth-quarter sales of sanofi-aventis' flu vaccine were up 70% over the same period in 2003.

Among its leading brands are allergy relief medicine Allegra, Plavix (marketed in the U.S. by Bristol-Myers Squibb), Lovenox, Ambien and Actonel (with Procter & Gamble Pharmaceuticals).

Like other big pharma companies, sanofi-aventis faces competition from generics. (The company is focusing on its own generic business for the European market.) The FDA recently approved generic equivalents of two of the company's drugs:

* Teva Pharmaceuticals Industries Ltd. will market a generic version of sanofi-aventis' anti-diabetic treatment Amaryl, which was nearing patent expiration anyway.

* Barr Laboratories is launching a generic version of DDAVP, an anti-diuretic sold by Aventis.

Despite these setbacks, business is good and probably will get better. Market analysts have described the company's pipeline as the "best in the industry." It has 128 products in development, including 48 entities in phase II or III clinical trial.

Two new drugs have the potential to reach blockbuster status: Exubera and Acomplia.

* In March 2005, sanofi-aventis and Pfizer filed a New Drug Application (NDA) for Exubera. It's the first dry-powder inhalation insulin drug for treating diabetes that's been submitted to the FDA.

* In June 2005, sanofi-aventis released results from the final clinical trials of Acomplia. Billed as a wonder drug, Acomplia is a weight-loss pill that also helps control blood sugar levels for diabetes treatment. It works by blocking hunger-inducing receptors in the brain and, in fat tissue, increasing the protein cytokine. When people don't have enough cytokine, it interferes with their insulin levels, putting them at higher risk of developing type 2 diabetes. And, because the area of the brain that controls hunger also controls other addictive behaviors, Acomplia may also help people stop smoking cigarettes.

These successes bode well for sanofi-aventis, but the company hasn't been without corresponding battles. It fiercely protects its intellectual properties by defending its patents in the courts--a practice that executives vow will continue. Last month, a U.S. court ruled in favor of generic producer Amphastar Pharmaceuticals in a trial alleging patent infringement of sanofi-aventis' Lovenox, sanofi-aventis is appealing that decision.

The company's strategy? Move promising products forward through the pipeline and force competitors to try to keep up.

COPYRIGHT 2005 Stagnito Communications
COPYRIGHT 2005 Gale Group

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