Document Detail


Fondaparinux sodium.
MedLine Citation:
PMID:  12532174     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fondaparinux (Org-31540 / SR-90107A) is a new drug chemically synthesized for treatment and prophylaxis of thromboembolic disease. Fondaparinux is a selective inhibitor of activated factor X. Its structure is the copy of the heparin pentasaccharide sequence, the shortest chain required for antithrombin inhibition of activated factor X without antithrombin action. Fondaparinux has no effect on coagulation tests and does not bind to platelet factor 4 or promote heparin-induced thrombocytopenia. Fondaparinux inhibits thrombin generation and the growth of thrombi in in vitro and in vivo models. Phase I trials have shown a 100% bioavailability after subcutaneous (s.c.) administration, a rapid onset of action and an approximate half-life of 13.5 h. Fondaparinux is cleared as an active substance by the kidneys. In elderly patients, renal clearance is reduced and the half-life is longer. The phase II Pentathlon trial demonstrated significant dose-dependent reductions in the frequency of venous thromboembolism in total hip-replacement patients and the optimal dose was determined to be 2.5 mg s.c./24 h. Four phase III trials have evaluated fondaparinux starting 6 hours after surgery compared with enoxaparin for prevention of venous thromboembolism following orthopedic surgery in 7,344 patients. The risk of thrombosis was reduced by 50% with fondaparinux and no differences were observed in death or severe bleeding. In a phase II trial, similar efficacy and incidence of major bleeding were seen with fondaparinux s.c. compared with dalteparin s.c. in the treatment of deep venous thrombosis. In patients with acute myocardial infarction, the efficacy of fondaparinux during fibrinolytic therapy was assessed in 326 patients who had acute coronary syndromes of less than a 6 hour duration, showing a slight but statistically not significant advantage for fondaparinux over unfractionated heparin in the coronary angiographies. There is currently no antidote for fondaparinux.
Authors:
J C Reverter
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Drugs of today (Barcelona, Spain : 1998)     Volume:  38     ISSN:  1699-3993     ISO Abbreviation:  Drugs Today     Publication Date:  2002 Mar 
Date Detail:
Created Date:  2003-01-17     Completed Date:  2003-03-25     Revised Date:  2006-10-26    
Medline Journal Info:
Nlm Unique ID:  101160518     Medline TA:  Drugs Today (Barc)     Country:  Spain    
Other Details:
Languages:  eng     Pagination:  185-94     Citation Subset:  IM    
Affiliation:
Hemotherapy and Hemostasis Department, Hospital Clinic, Barcelona, Spain. REVERTER@clinic.ub.es
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Coagulation / drug effects
Fibrinolytic Agents / adverse effects,  pharmacokinetics,  pharmacology,  therapeutic use*
Humans
Orthopedic Procedures
Polysaccharides / adverse effects,  pharmacokinetics,  pharmacology,  therapeutic use*
Postoperative Complications / blood,  prevention & control
Thromboembolism / prevention & control
Thrombosis / etiology,  prevention & control
Vascular Diseases / prevention & control
Venous Thrombosis / prevention & control
Chemical
Reg. No./Substance:
0/Fibrinolytic Agents; 0/Polysaccharides; 0/fondaparinux

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