Abstract
AIM OF THE STUDY To review the best evidence-based knowledge about the clinical pharmacology and use of fondaparinux. DESIGN OF THE STUDY Narrative review. RESULTS Fondaparinux is a synthetic pentasaccharide anticoagulant that binds selectively with high affinity to antithrombin and catalyses the inactivation of factor Xa, which results in a dose-dependent inhibition of thrombin generation. Fondaparinux does not bind to platelets or inhibit platelet aggregation, does not cross-react with antibodies to heparin-PF4 complexes (HIT antibodies) and has no effects on the activated partial thromboplastin time, prothrombin time and antithrombin levels. Fondaparinux shows a linear and highly predictable pharmacokinetic profile in humans, with very limited intraindividual and interindividual variability, which makes routine monitoring and dose adjustments unnecessary for the majority of the population. After subcutaneous iniection fondaparinux undergoes complete and dose-independent absorption; it is not significantly metabolized by the liver and does not interfere with cytochrome P450-mediated transformation of other drugs. Fondaparinux is almost entirely excreted unchanged in the urine with a half-life of approximately 17 hours, allowing for once-daily dosing. Its plasma clearance is reduced in patients with moderate or severe renal insufficiency. In the clinical trials and post-marketing surveillance fondaparinux shows an excellent tolerability profile, with a low incidence of major bleeding across a wide dose range and no cases of severe thrombocytopenia or heparin-induced thrombocytopenia (HIT). CONCLUSIONS Fondaparinux has been approved in many countries for use in thromboprophylaxis after major orthopedic surgery and in medical patients, and for the treatment of sintomatic venous thromboembolism (deep venous thrombosis and hemodynamically stable pulmonary embolism) and acute coronary syndromes (unstable angina, and acute miocardial infartion, with or without ST elevation). In these clinical settings fondaparinux is at least as effective and safe as unfractionated heparin or low molecular weight heparins, and may be easier to use.