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Fondaparinux

The traditional anticoagulant drugs warfarin, unfractionated heparin (UFH) and low molecular weight heparin (LMWH) have a number of limitations, including issues regarding laboratory monitoring, food and drug interactions, and a narrow therapeutic window. Ideal characteristics of new anticoagulant drugs include: good bioavailability, no food or drug interaction, rapid onset of action, a wide therapeutic window, a predictable anticoagulant response making laboratory monitoring unnecessary, availability of an antidote, and effectiveness and safety at least equivalent to the currently available drugs. Whereas the older anticoagulant drugs have an effect on multiple factors in the coagulation pathway, new drugs selectively inhibit a single coagulation factor.

Factor Xa inhibitors can be administered either orally or parenterally and inhibit Factor Xa indirectly since their effect is mediated through antithrombin. Fondaparinux is a pentasaccharide obtained by chemical synthesis. It binds to antithrombin resulting in a conformational change in the antithrombin molecule, thereby greatly potentiating its inhibition of factor Xa. It is administered once daily by subcutaneous injection in a fixed dose, and no laboratory monitoring is required. This drug shows no cross-reactivity with heparin induced thrombocytopenia (HIT) antibodies, and has not been associated with any instance of HIT.

Fondaparinux has been shown to be effective in the prevention of venous thromboembolism (VTE) following orthopedic surgery. A meta-analysis of four large trials (Arch Int Med. 2002;162:1833-40) showed that fondaparinux was significantly more effective than LMWH in reducing the incidence of VTE after hip replacement, hip fracture surgery and major knee surgery, with an overall 55% decrease in risk reduction compared with LMWH. Fondaparinux was shown in other trials to be at least as effective and safe as LMWH/UFH in the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), in the prevention of VTE after abdominal surgery, and in the treatment of acute coronary syndrome. Fondaparinux was the first selective factor Xa inhibitor to be FDA approved as an anticoagulant.

Fondaparinux, in both prophylactic and therapeutic doses, prolongs the prothrombin time (PT) by approximately 1 second, and the APTT by approximately 4-5 seconds, however laboratory monitoring is not indicated. The drug is excreted by the kidneys, and has a half-life of 17 hours. No antidote is available.

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