Anticoagulant fondaparinux sodium

Blood clots, or thromboembolism, are a major complication that can arise during surgical procedures. Numerous antithrombotics are available, but side-effects remain a problem and dosing regimens can be difficult to establish.

A new antithrombotic is being developed by Sanofi-Synthelabo and Organon. Fondaparinux, is a naturally-occurring pentasaccharide that is a potent, selective inhibitor of activated Factor X that is structurally related to the heparins.1 This pentasaccharide has been found to be the shortest fragment that catalyses the antithrombin-mediated inhibition of activated Factor X, without having any antithrombin effects.

Numerous Phase III clinical trials have been carried out on the drug's use post-operatively, including four comparing it with the low molecular weight heparin enoxaparin. These four trials encompassed more than 7,000 patients undergoing orthopaedic surgery around the world. The double blind randomised studies compared fondaparinux, administered subcutaneously in a dose of 2.5mg/24hrs starting 6 hours after surgery, and a 30mg subcutaneous dose of enoxaparin every 12 hours post-operatively. The primary efficacy endpoint was the occurrence of a venous embolism up to day 11 after surgery, and the main safety outcome was a major bleed. Patients receiving fondaparinux were 50% less likely to develop a venous thrombosis than those given enoxaparin, with no important differences between the two regimes with death, and bleeding.2

Fondaparinux is also being investigated as a treatment for deep vein thrombosis. In a randomised parallel group dose ranging Phase II clinical trial, three different doses (5, 7.5 or 10mg/day) were given subcutaneously, or 100 IU every 12 hrs subcutaneously of the low molecular weight heparin dalteparin.3 The two drugs had a similar efficacy in reducing the clot, with similar incidence of major bleeding, but those given fondaparinux were less likely to suffer a recurrence.