Fondaparinux

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Fondaparinux
Fondaparinux.svg
Clinical data
Trade names Arixtra
AHFS/Drugs.com monograph
Licence data EMA:Link, US FDA:link
Legal status POM (UK) -only (US)
Routes subcutaneous
Pharmacokinetic data
Bioavailability N/A
Protein binding 94%
Metabolism renally excreted unchanged
Half-life 17-21 hours
Identifiers
CAS number 114870-03-0 YesY
ATC code B01AX05
PubChem CID 636380
DrugBank DB00569
ChemSpider 552174 YesY
UNII J177FOW5JL YesY
ChEMBL CHEMBL1201202 N
Chemical data
Formula C31H43N3Na10O49S8 
Mol. mass 1726.77 g/mol
 N (what is this?)  (verify)

Fondaparinux (trade name Arixtra) is an anticoagulant medication chemically related to low molecular weight heparins. It is marketed by GlaxoSmithKline. A generic version developed by Alchemia is marketed within the US by Dr. Reddy's Laboratories.

Structure and mechanism[edit]

Fondaparinux is a synthetic pentasaccharide Factor Xa inhibitor. Apart from the O-methyl group at the reducing end of the molecule, the identity and sequence of the five monomeric sugar units contained in fondaparinux is identical to a sequence of five monomeric sugar units that can be isolated after either chemical or enzymatic cleavage of the polymeric glycosaminoglycans heparin and heparin sulfate (HS). Within heparin and heparin sulfate this monomeric sequence is thought to form the high affinity binding site for the anti-coagulant factor antithrombin III (ATIII). Binding of heparin/HS to ATIII has been shown to increase the anti-coagulant activity of antithrombin III 1000 fold. In contrast to heparin, fondaparinux does not inhibit thrombin.

Administration[edit]

Fondaparinux is given subcutaneously daily. Clinically, it is used for the prevention of deep vein thrombosis in patients who have had orthopedic surgery as well as for the treatment of deep vein thrombosis and pulmonary embolism.

Comparison to other agents[edit]

One potential advantage of fondaparinux over LMWH or unfractionated heparin is that the risk for heparin-induced thrombocytopenia (HIT) is substantially lower. Furthermore, there have been case reports of fondaparinux being used to anticoagulate patients with established HIT as it has no affinity to PF-4. However, its renal excretion precludes its use in patients with renal dysfunction.

Unlike direct factor Xa inhibitors, it mediates its effects indirectly through antithrombin III, but unlike heparin, it is selective for factor Xa.[1]

Uses[edit]

Fondaparinux is similar to enoxaparin in reducing the risk of ischemic events at nine days, but it substantially reduces major bleeding and improves long term mortality and morbidity.[2]

It has been investigated for use in conjunction with streptokinase.[3]

Chemical structure[edit]

Abbreviations[edit]

  • GlcNS6S = 2-deoxy-6-O-sulfo-2-(sulfoamino)-α-D-glucopyranoside
  • GlcA = β-D-glucopyranuronoside
  • GlcNS3,6S = 2-deoxy-3,6-di-O-sulfo-2-(sulfoamino)-α-D-glucopyranosyl
  • IdoA2S = 2-O-sulfo-α-L-idopyranuronoside
  • GlcNS6SOMe = methyl-O-2-deoxy-6-O-sulfo-2-(sulfoamino)-α-D-glucopyranoside

The sequence of monosaccharides is D-GlcNS6S-α-(1,4)-D-GlcA-β-(1,4)-D-GlcNS3,6S-α-(1,4)-L-IdoA2S-α-(1,4)-D-GlcNS6S-OMe, as shown in the following structure:

Fondaparinux

References[edit]

External links[edit]