Fondaparinux (ARIXTRA)

David Goldemund M.D.
Updated on 18/07/2024, published on 24/01/2022
  • fondaparinux is a synthetic pentasaccharide that acts as an indirect factor Xa inhibitor (by binding to antithrombin)
  • it is administered subcutaneously (SC) and appears to be more effective than enoxaparin in preventing VTE without the increased risk of bleeding
  • advantage of fondaparinux over LMWH or unfractionated heparin (UFH) is significantly lower risk of heparin-induced thrombocytopenia (HIT)


  • 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


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  • 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
  • agents that may increase the risk of bleeding should be discontinued prior to initiation of therapy with fondaparinux unless these agents are essential
    • if coadministration is necessary, patients should be monitored closely for bleeding
  • fondaparinux sodium does not significantly bind to plasma proteins other than AT III ⇒ no drug interactions by protein-binding displacement are expected


  • VTE prevention during orthopedic procedures on the lower extremities  (hip fracture surgery, hip or 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 heparininduced thrombocytopenia (HIT)
    • treatment of heparin-induced thrombocytopenia (HIT)
      • no affinity to PF4
    • anticoagulation during a nonSTsegmentelevation myocardial infarction (nonSTEMI)


  • severe renal impairment (creatinine clearance < 30 mL/min)
  • active clinically significant bleeding
  • bacterial endocarditis
  • known hypersensitivity to fondaparinux (e.g., angioedema, anaphylactoid/anaphylactic reactions)
  • thrombocytopenia associated with a positive in vitro test for anti-platelet antibody in the presence of fondaparinux
  • body weight <50 kg (for VTE prophylaxis, relative CI)


VTE prophylaxis


  • 2.5 mg SC once daily
    • the maximum concentration of 0.39-0.5 mg/L is reached after 3 hours
    • postoperative thromboprophylaxis should be started > 6-8 h after skin closure
    • the first dose may be given the morning after surgery
  • duration of therapy
    • surgical procedures
      • abdominal surgery: at least 5-9 days
      • hip replacement: 11 days
      • hip or knee arthroplasty: 10-14 days
      • in the case of hip fracture surgery, VTE risks persist for a longer period – consider continuing therapy for 24 days after surgery
    • internal medicine patients – 6-14 days
    • thrombophlebitis – 30-45 days

Reduction of prophylactic dose

  • renal impairment
    • creatinine clearance (CrCl) >50 mL/min – no dose adjustment required
    • CrCl  20-50 mL/min –  1.5 mg once daily
    • CrCl < 20 mL/min – contraindicated
  • hepatopathy
    • mild/moderate hepatic impairment – no dose adjustment required
    • severe hepatic impairment – use cautiously; the product has not been tested in this population
  • body weight <50 kg
    • increased risk of bleeding (elimination of fondaparinux is reduced in low body weight)
    • use with caution
VTE/PE therapy


  • the dose depends on the patient’s weight
    • 50-100 kg: 7.5 mg SC once daily
    • < 50 kg: SC 5 mg SC once daily
    • > 100 kg: 10 mg SC once daily
  • according to the MATISSE-DVT and MATISSE-PE trials, fondaparinux is at least as effective and safe as LMWH (compared to enoxaparin) and better than UFH
HIT/HITT therapy


  • the dose depends on the patient’s weight
    • 50-100 kg: 7.5 mg SC once daily
    • < 50 kg: 5 mg SC once daily
    • > 100 kg: 10 mg SC once daily

→ heparin-induced thrombocytopenia (HIT)

Neutralization of the effect

  • canceling the effect of fondaparinux is difficult, as with LMWH, because a specific antidote is not available
  • in cases of fondaparinux-related hemorrhage, consider coagulation factors supplementation  (limited clinical data)  → neutralization of anticoagulant effect


  • fondaparinux anti-Xa assay can be used to monitor fondaparinux therapy
  • it measures the inhibitory effect of the fondaparinux-AT complex on FXa
    • an optical method based on the principle of chromogenic substrates without the addition of exogenous antithrombin
    • the analysis depends on the amount of AT in the plasma
  • sampling should be drawn 3-4 hours after drug administration when the highest anti-Xa activity is reached (peak steady-state plasma concentration)
    • prophylactic dose 2.5 mg SC once daily … 0.39 – 0.50 mg/L (μg/mL)
    • therapeutic dose 7.5 mg SC once daily  …  1.2 – 1.26 mg/L (μg/mL)


  • most common adverse events include:
    • bleeding
    • chest pain
    • confusion, convulsions
    • arrhythmia
    • numbness or tingling in extremities

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