Fondaparinux, a synthetic pentasaccharide, acts as a selective, indirect inhibitor of factor Xa. The compound represents the minimal binding sequence of heparin required for binding to antithrombin III and binds exclusively to antithrombin III, producing a conformational change that increases the anti-factor Xa of antithrombin by at least 270-fold. This effect results in a reduction in thrombin (factor IIa) generation and thrombus development without inhibiting thrombin itself. Fondaparinux has no significant effect on prothrombin time (PT), bleeding time, or activated partial thromboplastin time (aPTT).
The approval of fondaparinux was based on several randomized, controlled clinical trials involving 8,000 patients undergoing hip fracture, hip replacement, or knee replacement surgeries. In one double-blind clinical trial with 1,711 patients undergoing hip fracture surgery, 8.3% of patients given fondaparinux developed DVT or pulmonary embolism, compared with 19.1% of patients given enoxaparin. Likewise, in two controlled trials involving 2,275 patients undergoing hip replacement, 4.1%-6.1% of patients receiving fondaparinux developed venous thromboembolism, compared with 8.3%-9.2% of enoxaparin-treated patients. In another trial of 1,049 patients undergoing knee replacement, 12.5% of fondaparinux-treated patients developed thromboembolic events compared with 27.8% of enoxaparin-treated patients. Fondaparinux is more effective than enoxaparin in preventing venous thromboembolism in patients undergoing surgery for hip fracture or total hip replacement.
|Protein binding||94% (antithrombin III)|
|Volume of distribution||7-11 L|
The most common adverse reactions during fondaparinux administration were bleeding complications, with major bleeding episodes occurring in 2%-3% of patients. Other most common adverse reactions included anemia (19.6%), fever (13.6%), and nausea (11.3%).
Fondaparinux, a synthetic pentasaccharide, has demonstrated efficacy in the prevention of venous thromboembolic events following orthopedic surgery. Unlike unfractionated heparin, fondaparinux does not interact with platelet factor IV, which minimizes the risk of thrombocytopenia, and it has a long half-life, which allows for once-daily dosing. Fondaparinux appears to be more effective than enoxaparin, but comparisons to other anticoagulants are not available. It is the first antithrombotic approved for the prevention of DVT in hip fracture surgery. Like other low molecular weight heparins, fondaparinux does not require routine monitoring because of its highly predictable therapeutic effect. This new agent is also being studied for the treatment of venous thromboembolism, pulmonary embolism, and acute coronary syndromes. Fondaparinux received a "priority" review by the FDA.
Published April 2002. Content based on medical literature and product information available at the time.
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