ADD-ONS / MEDICATION / ANTICOAGULANT THERAPY
Fondaparinux (ARIXTRA)
Created 24/01/2022, last revision 26/04/2023
- fondaparinux is a synthetic pentasaccharide that acts as an indirect factor Xa inhibitor (by binding to antithrombin)
- it is administered subcutaneously and appears to be more effective than enoxaparin in VTE prophylaxis without the increased risk of bleeding
- advantage of fondaparinux over LMWH or unfractionated heparin is substantially lower risk of heparin-induced thrombocytopenia (HIT)
Pharmacodynamics
- fondaparinux selectively and indirectly (by binding to antithrombin) inhibits factor Xa ⇒ inhibition of thrombin generation [Turpie, 2008]
- does not affect prothrombin or platelets
- after activating antithrombin III (AT III) and increasing its natural ability to inactivate FXa, fondaparinux is released from the AT III/FXa complex and can activate other antithrombin molecules
- affects only factor X (compared to LMWH/heparin, it lacks the longer carbohydrate chain required to bind to thrombin)
- at a dose of 2.5 mg, fondaparinux does not affect common coagulation tests, such as activated partial thrombin time (aPTT), activated clotting time (ACT) or prothrombin time (PT)/international normalized ratio (INR) plasma tests, or bleeding time or fibrinolytic activity
- rarely, increased aPTT was reported

Pharmacokinetics
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Interactions
- the concomitant use of oral anticoagulants (warfarin), platelet inhibitors (acetylsalicylic acid), NSAIDs (piroxicam), and digoxin does not significantly affect the pharmacokinetics/pharmacodynamics of fondaparinux sodium
- fondaparinux neither influences the pharmacodynamics of warfarin, acetylsalicylic acid, piroxicam, and digoxin, nor the pharmacokinetics of digoxin at a steady-state
- agents that may enhance the risk of bleeding should be discontinued before initiation of therapy with fondaparinux unless these agents are essential
- if co-administration is necessary, monitor patients closely for hemorrhage
- fondaparinux sodium does not bind significantly to plasma proteins other than AT III ⇒ no drug interactions by protein-binding displacement are expected
Indications
- VTE prevention during orthopedic procedures on the lower extremities (hip fracture, hip replacement, knee replacement)
- VTE prevention patients undergoing abdominal surgery who are expected to be at high risk of thromboembolic complications
- treatment of acute symptomatic spontaneous thrombophlebitis
- treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) in adult patients, except in hemodynamically unstable patients or patients requiring thrombolysis or pulmonary embolectomy
- off-label indications
- DVT prophylaxis in medically ill (including cancer patients), who are considered to be at increased risk of VTE
- DVT prophylaxis in patients with a history of heparin–induced thrombocytopenia (HIT)
- treatment of heparin-induced thrombocytopenia (HIT)
- no affinity to PF4
- anticoagulation during a non–ST–segment–elevation myocardial infarction (non–STEMI)
Contraindications
- severe renal impairment (creatinine clearance < 20 mL/min)
- active, clinically significant bleeding
- acute infective endocarditis
- known hypersensitivity to fondaparinux
Neutralization of the effect
- canceling the effect of fondaparinux is difficult, as with LMWH, the antagonist is unknown
- andexanet has approval for the reversal of the direct oral factor Xa inhibitors rivaroxaban and apixaban only; the dose for the reversal of fondaparinux has not been established
- in bleeding occurs, consider coagulation factors supplementation (limited clinical data)
- activated prothrombin complex concentrates (aPCC)
- fresh frozen plasma
- recombinant activated factor VII (rFVIIa)
- fondaparinux is dialyzable
Monitoring
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