Fondaparinux (Arixtra)

Indications

Acute Coronary Syndrome (ACS) (see Coronary Artery Disease, [[Coronary Artery Disease]])

  • xxxx

Systemic Embolism Prophylaxis in Atrial Fibrillation (see Atrial Fibrillation, [[Atrial Fibrillation]])

  • xxxx

Venous Thromboembolism-Deep Venous Thrombosis (DVT)/Acute Pulmonary Embolism (PE) (see Deep Venous Thrombosis, [[Deep Venous Thrombosis]] and Acute Pulmonary Embolism, [[Acute Pulmonary Embolism]])

  • xxxx

Deep Venous Thrombosis (DVT) Prophylaxis After Knee/Hip Replacement (see Deep Venous Thrombosis, [[Deep Venous Thrombosis]])

  • Systematic Review Comparing Novel Oral and Other Anticoagulants (Fondaparinux, Dabigatran, Rivaroxaban, Apixaban) to Enoxaparin Used as Venous Thromboembolism Prophylaxis After Major Orthopedic Surgery (Ann Vasc Surg, 2013) [MEDLINE]
    • Novel Anticoagulants Can Be Considered as Alternatives to Enoxaparin, Depending on Their Individual Clinical Characteristics and Cost-Effectiveness
    • Primary Efficacy (Any DVT, Non-Fatal PE, or All-Cause Mortality) Favored Fondaparinux and Rivaroxaban Over Enoxaparin
    • Compared to Enoxaparin, the Bleeding Risk was Similar for All Agents, Except Fondaparinux (Which Manifested a Significantly Higher Any-Bleeding Risk) and Apixaban (Which Manifested a Lower Any-Bleeding Risk)

Heparin-Induced Thrombocytopenia (HIT) (see Heparin-Induced Thrombocytopenia, [[Heparin-Induced Thrombocytopenia]])

  • Historical Perspective: although fondaparinux has been used to treat HIT, there are case reports of it both causing and exacerbating HIT
    • Case Report of Fondaparinux Exacerbating HIT (Am J Hematol, 2015) [MEDLINE]
  • Clinical Efficacy
    • Small Retrospective Review of the Use of Fondaparinux in HIT (Clin Appl Thromb Hemost, 2016) [MEDLINE]
      • Fondaparinux Appears to Be as Safe and Effective as Direct Thrombin Inhibitors in the Treatment of HIT

Pharmacology

  • Synthetic Pentasaccharide Factor Xa Inhibitor (see Factor Xa Inhibitors, [[Factor Xa Inhibitors]])

Metabolism

  • Renal

Administration

  • SQ

Dose Adjustment

  • Hepatic
  • Renal

Effect on Anticoagulation Tests

  • Prothrombin Time (PT)/International Normalized Ratio (INR) (see Prothrombin Time, [[Prothrombin Time]]): no change
    • Fondaparinux is an Indirect Thrombin Inhibitor and Should Theoretically Prolong the INR: however, most INR assay reagents contain heparin-binders which block the effect of heparin (or similar agents) at concentrations <1 unit/mL -> therefore, at heparin concentration of >1 unit/mL, the INR may be prolonged
  • Partial Thromboplastin Time (PTT) (see Partial Thromboplastin Time, [[Partial Thromboplastin Time]]): no change-prolonged
  • Anti-Factor Xa Activity (see Anti-Factor Xa Activity, [[Anti-Factor Xa Activity]]): prolonged

Adverse Effects

Hematologic Adverse Effects

Heparin-Induced Thrombocytopenia (HIT) (see Heparin-Induced Thrombocytopenia, [[Heparin-Induced Thrombocytopenia]])

  • Epidemiology: cases of fondaparinux both causing and exacerbating HIT have been reported
    • Case Report of Fondaparinux Exacerbating HIT (Am J Hematol, 2015) [MEDLINE]
  • Clinical Efficacy
    • Small Retrospective Review of the Use of Fondaparinux in HIT (Clin Appl Thromb Hemost, 2016) [MEDLINE]
      • Fondaparinux Appears to Be as Safe and Effective as Direct Thrombin Inhibitors in the Treatment of HIT

Hemorrhagic Adverse Effects


References

  • Fondaparinux as a treatment option for heparin-induced thrombocytopenia. Pharmacotherapy. 2007 Jun;27(6):921-6 [MEDLINE]
  • Fondaparinux and the management of heparin-induced thrombocytopenia: the journey continues. Ann Pharmacother. 2009 Oct;43(10):1636-46. doi: 10.1345/aph.1M136. Epub 2009 Sep 8 [MEDLINE]
  • Fondaparinux treatment of acute heparin-induced thrombocytopenia confirmed by the serotonin-release assay: a 30-month, 16-patient case series. J Thromb Haemost. 2011 Dec;9(12):2389-96. doi: 10.1111/j.1538-7836.2011.04487 [MEDLINE]
  • Systematic review of randomized controlled trials of new anticoagulants for venous thromboembolism prophylaxis in major orthopedic surgeries, compared with enoxaparin. Ann Vasc Surg. 2013 Apr;27(3):355-69. doi: 10.1016/j.avsg.2012.06.010. Epub 2013 Jan 23 [MEDLINE]
  • Severe and persistent heparin-induced thrombocytopenia despite fondaparinux treatment. Am J Hematol. 2015 Jul;90(7):675-8. doi: 10.1002/ajh.23971. Epub 2015 Feb 27 [MEDLINE]
  • Management of heparin-induced thrombocytopenia. Curr Opin Hematol. 2016 Jul 1. [MEDLINE]
  • Efficacy and Safety of Fondaparinux in Patients With Suspected Heparin-Induced Thrombocytopenia. Clin Appl Thromb Hemost. 2016 May 13. pii: 1076029616646873 [MEDLINE]