Fondaparinux: a synthetic heparin pentasaccharide as a new antithrombotic agent.
Fondaparinux (Arixtra, Sanofi-Synthélabo/Organon) is the first of a new class of antithrombotic agents distinct from low molecular weight heparins (LMWHs) and heparin. It is a chemically synthetic pentasaccharide mimicking the site of heparin that binds to antithrombin III (AT). It exhibits only factor (F) Xa (FXa) inhibitor activity via binding to AT, which in turn inhibits thrombin generation. In contrast to heparin and LMWH, plasma anti-Xa activity corresponds directly to levels of fondaparinux. It does not release tissue factor pathway inhibitor (TFPI). There is nearly complete bioavailability by the sc. route, rapid onset of action, a prolonged half-life in both iv. and sc. (14 - 20 h) dosing regimens and no metabolism preceding renal excretion. Phase IIb clinical studies have identified a dose of 2.5 mg once-daily for prophylaxis of venous thrombosis. Four Phase III studies (n > 7000) have demonstrated a combined 50% relative risk reduction of venous thromboembolic events in orthopaedic surgery patients in comparison to the LMWH, enoxaparin. Haemmorrhagic complications for fondaparinux were either comparable to or higher than those for LMWH. The activated partial thromboplastin time (aPTT) is not affected by fondaparinux. At present, laboratory monitoring is not recommended. Clinical trials for treatment of established thrombosis, coronary syndromes and adjunct to thrombolytic therapy are in progress.
Walenga
Jeanine M
JM
Department of Pathology, Loyola University Medical Center, 2160 S. First Avenue, Maywood, Illinois 60153, USA. jwaleng@lumc.edu
Jeske
Walter P
WP
Samama
M Michel
MM
Frapaise
F Xavier
FX
Bick
Rodger L
RL
Fareed
Jawed
J
D000818:Animals; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077425:Fondaparinux; D006801:Humans; D011134:Polysaccharides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000188:drug therapy*
D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D011134:Polysaccharides; D000077425:Fondaparinux