Arixtra - General Information
Fondaparinux (Arixtra) is an anticoagulant medication. It contains a synthetic pentasaccharide. 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 heparan sulfate (HS). Within heparin and heparan 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.
Clinically, fondaparinux 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.
Pharmacology of Arixtra
Fondaparinux is a synthetic and specific inhibitor of activated Factor X (Xa) indicated for the prophylaxis of deep vein thrombosis, which may lead to pulmonary embolism. Fondaparinux is also indicated for the treatment of acute deep vein thrombosis when administered in conjunction with warfarin, and the treatment of acute pulmonary embolism when administered in conjunction with warfarin. Fondaparinux does not inactivate thrombin (activated Factor II) and has no known effect on platelet function. At the recommended dose, Fondaparinux does not affect fibrinolytic activity or bleeding time.
Arixtra for patients
In clinical studies performed with Fondaparinux, the concomitant use of oral anticoagulants
(warfarin), platelet inhibitors (acetylsalicylic acid), NSAIDs (piroxicam), and digoxin did
not significantly affect the pharmacokinetics/pharmacodynamics of fondaparinux sodium. In
addition, Fondaparinux neither influenced the pharmacodynamics of warfarin, acetylsalicylic
acid, piroxicam, and digoxin, nor the pharmacokinetics of digoxin at steady state.
Agents that may enhance the risk of hemorrhage should be discontinued prior to initiation
of Fondaparinux therapy. If co-administration is essential, close monitoring may be appropriate.
In an in vitro study in human liver microsomes, inhibition of CYP2A6 hydroxylation of coumarin
by fondaparinux (200 m m M i.e., 350 mg/L) was 17-28%. Inhibition of the other isozymes evaluated
(CYPs 2A1, 2C9, 2C19, 2D6, 3A4, and 3E1) was 0-16%. Since fondaparinux does not markedly inhibit
CYP450s (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4) in vitro, fondaparinux
sodium is not expected to significantly interact with other drugs in vivo by inhibition of
metabolism mediated by these isozymes.
Since fondaparinux sodium does not bind significantly to plasma proteins other than ATIII, no
drug interactions by protein-binding displacement are expected.
Fondaparinux injection is contraindicated in patients with severe renal impairment (creatinine
clearance <30 mL/min). Fondaparinux is eliminated primarily by the kidneys, and such patients
are at increased risk for major bleeding episodes.
Fondaparinux prophylactic therapy is contraindicated in patients with body weight <50 kg undergoing
hip fracture, hip replacement or knee replacement surgery, and abdominal surgery. During the
randomized clinical trials of prophylaxis in the peri-operative period following hip fracture,
hip replacement, or knee replacement surgery, occurrence of major bleeding was doubled in patients
with a body weight <50 kg compared with those with a body weight 50 kg (5.4% versus 2.1%). In the
clinical trial in patients undergoing abdominal surgery, the major bleeding rate was also higher
in patients with a body weight <50 kg as compared to those with a body weight 50 kg (5.3% versus 3.3%),
The use of Fondaparinux is contraindicated in patients with active major bleeding,
bacterial endocarditis, in patients with thrombocytopenia associated with a positive in vitro
test for anti-platelet antibody in the presence of fondaparinux sodium, or in patients with
known hypersensitivity to fondaparinux sodium.
Fondaparinux is also contraindicated in patients with hypersensitivity to fondaparinux.
Additional information about Arixtra
Arixtra Indication: For the treatment of prophylaxis of deep vein thrombosis.
Mechanism Of Action: The antithrombotic activity of Fondaparinux is the result of antithrombin III (ATIII)-mediated selective inhibition of Factor Xa. By selectively binding to ATIII, Fondaparinux potentiates (about 300 times) the innate neutralization of Factor Xa by ATIII. Neutralization of Factor Xa interrupts the blood coagulation cascade and thus inhibits thrombin formation and thrombus development.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Fondaparinux sodium
Synonyms: Not Available
Drug Category: Anticoagulants; Antithrombotics
Drug Type: Small Molecule; Approved; Investigational
Other Brand Names containing Fondaparinux sodium: Arixtra; Fondaparinux; fondaparinux sodium;
Toxicity (Overdose): Not Available
Protein Binding: 94%
Biotransformation: Not Available
Half Life: 17-21 hours
Dosage Forms of Arixtra: Solution Subcutaneous
Chemical IUPAC Name: decasodium (2R,3S,4S,5R,6R)-3-[(2R,3R,4R,5R,6R)-5-[(2R,3R,4R,5S,6S)-6-carboxylato-5-[(2R,3R,4R,5S,6R)-4,5-dihydroxy-3-(sulfonatoamino)-6-(sulfonatooxymethyl)oxan-2-yl]oxy-3,4-dihydroxyoxan-2-yl]oxy-3-(sulfonatoamino)-4-sulfonatooxy-6-(sulfonatooxymethyl)oxan-2-yl]oxy-4-hydroxy-6-[(2R,3S,4R,5R,6S)-4-hydroxy-6-methoxy-5-(sulfonatoamino)-2-(sulfonatooxymethyl)oxan-3-yl]oxy-5-sulfonatooxyoxane-2-carboxylate
Chemical Formula: C31H43N3Na10O49S8
Fondaparinux sodium on Wikipedia: http://en.wikipedia.org/wiki/Fondaparinux_sodium
Organisms Affected: Humans and other mammals