A Comprehensive Monograph on Fondaparinux Sodium

Executive Summary

Fondaparinux sodium, marketed principally under the brand name Arixtra®, represents a seminal advancement in anticoagulant therapy as the first-in-class synthetic pentasaccharide and a selective indirect inhibitor of activated coagulation Factor X (Factor Xa). Its development marks a significant departure from traditional, biologically derived anticoagulants such as unfractionated heparin (UFH) and low-molecular-weight heparins (LMWH), offering a targeted mechanism of action with a highly predictable pharmacological profile.[1]

The core pharmacological attribute of fondaparinux is its unique mechanism, which involves selectively binding to and potentiating the activity of antithrombin III (ATIII). This action amplifies the natural neutralization of Factor Xa by approximately 300-fold, thereby inhibiting the coagulation cascade upstream of thrombin generation. Crucially, fondaparinux does not directly or indirectly inhibit thrombin (Factor IIa), a key differentiator from heparins.[1] This targeted action, combined with its nature as a single, pure chemical entity, results in a highly predictable pharmacokinetic profile. This profile is characterized by 100% bioavailability following subcutaneous administration, minimal protein binding outside of ATIII, no hepatic metabolism, and a long elimination half-life of 17-21 hours, which permits convenient once-daily dosing without the need for routine coagulation monitoring.[6]