Drugs & Therapy Perspectives

, Volume 34, Issue 11, pp 507–512 | Cite as

Andexanet alfa in the treatment of acute major bleeding related to apixaban and rivaroxaban: a profile of its use in the USA

  • Young-A Heo
Adis Drug Q&A


Andexanet alfa (Andexxa®), a first-in-class recombinant modified factor Xa protein, is currently the only specific agent available to reverse life-threatening or uncontrolled bleeding with the factor Xa inhibitors apixaban and rivaroxaban. Andexanet alfa acts as a decoy and competes with endogenous factor Xa to bind factor Xa inhibitors, thereby reversing the anticoagulant effects of factor Xa inhibitors, and restoring the activity of endogenous factor Xa. In adults with major bleeding associated with the use of apixaban or rivaroxaban, intravenous administration of andexanet alfa effectively and rapidly reduces anti-factor Xa levels, with reduced levels being maintained during continued treatment. The tolerability profile of andexanet alfa in patients is generally similar to that reported of other approved anticoagulation reversal agents. With the known increased risk of thromboembolic events following andexanet alfa treatment, anticoagulant therapy should be resumed as soon as medically appropriate.



The manuscript was updated from Drugs 2018;78(10):1049–55 [21], and was reviewed by: J. E. Ansell, Hofstra Northwell School of Medicine, Hempstead, NY, USA; N. Ali, Department of Pathology and Laboratory Medicine/Oncology, The Aga Khan University Hospital, Karachi, Pakistan; J. D. Douketis, Department of Medicine, McMaster University, Hamilton, ON, Canada. During the peer review process, Portola Pharmaceuticals, Inc., the marketing-authorization holder of andexanet alfa, was offered an opportunity to provide a scientific accuracy review of their data. Changes resulting from comments received will be made on the basis of scientific and editorial merit.

Compliance with ethical standards


The preparation of this review was not supported by any external funding.

Conflict of interest

Y.-A. Heo is an employee of Adis/Springer, is responsible for the article content and declares no conflicts of interest.


  1. 1.
    Milling TJ Jr, Frontera J. Exploring indications for the use of direct oral anticoagulants and the associated risks of major bleeding. Am J Manag Care. 2017;23(4 Suppl):S67–80.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Greinacher A, Thiele T, Selleng K. Reversal of anticoagulants: an overview of current developments. Thromb Haemost. 2015;113(5):931–42.CrossRefGoogle Scholar
  3. 3.
    Milling TJ, Clark CL, Feronti C, et al. Management of factor Xa inhibitor-associated life-threatening major hemorrhage: a retrospective multi-center analysis. Am J Emerg Med. 2018;36:396–402.CrossRefGoogle Scholar
  4. 4.
    Levy JH, Douketis J, Weitz JI. Reversal agents for non-vitamin K antagonist oral anticoagulants. Nat Rev Cardiol. 2018;15(5):273–81.CrossRefGoogle Scholar
  5. 5.
    Dabi A, Koutrouvelis AP. Reversal strategies for intracranial hemorrhage related to direct oral anticoagulant medications. Crit Care Res Pract. 2018;2018(4907164):1–11.Google Scholar
  6. 6.
    Ansell JE. Reversing the effect of oral anticoagulant drugs: established and newer options. Am J Cardiovasc Drugs. 2016;16(3):163–70.CrossRefGoogle Scholar
  7. 7.
    Nafee T, Aslam A, Chi G, et al. Andexanet alfa for the reversal of anticoagulant activity in patients treated with direct and indirect factor Xa inhibitors. Expert Rev Cardiovasc Ther. 2017;15(4):237–45.CrossRefGoogle Scholar
  8. 8.
    Andexxa (coagulation factor Xa (recombinant), inactivated-zhzo) lyophilized powder for solution for intravenous injection: US prescribing information. South San Franciso: Portola Pharmaceuticals, Inc.; 2018.Google Scholar
  9. 9.
    Kaatz S, Bhansali H, Gibbs J, et al. Reversing factor Xa inhibitors: clinical utility of andexanet alfa. J Blood Med. 2017;8:141–9.CrossRefGoogle Scholar
  10. 10.
    Lu G, Hollenbach SJ, Baker DC, et al. Preclinical safety and efficacy of andexanet alfa in animal models. J Thromb Haemost. 2017;15(9):1747–56.CrossRefGoogle Scholar
  11. 11.
    Lu G, DeGuzman FR, Hollenbach SJ, et al. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med. 2013;19(4):446–51.CrossRefGoogle Scholar
  12. 12.
    Grottke O, Akman N, Conley PB, et al. The impact of andexanet alfa in a porcine polytrauma model under apixaban anticoagulation: investigation of hemostatic safety and efficacy [abstract no. 20205]. Circulation. 2017;136(Suppl 1).Google Scholar
  13. 13.
    Siegal D, Lu G, Leeds JM, et al. Safety, pharmacokinetics, and reversal of apixaban anticoagulation with andexanet alfa. Blood Adv. 2017;1(21):1827–38.CrossRefGoogle Scholar
  14. 14.
    Mark C, Vandana M, Michael K, et al. A phase 2 randomized, double-blind, placebo-controlled trial demonstrating reversal of rivaroxaban-induced anticoagulation in healthy subjects by andexanet alfa (PRT064445), an antidote for FXA inhibitors [abstract]. Blood. 2013;122(21):3.Google Scholar
  15. 15.
    Siegal DM, Curnutte JT, Connolly SJ, et al. Andexanet alfa for the reversal of factor Xa inhibitor activity. N Engl J Med. 2015;373(25):2413–24.CrossRefGoogle Scholar
  16. 16.
    Lu G, Lin J, Curnutte JT, et al. Effect of andexanet-tissue factor pathway inhibitor (TFPI) interaction on in vitro clot formation and lysis via different coagulation pathways [slide presentation]. In: International Society on Thrombosis and Haemostasis. 2018.Google Scholar
  17. 17.
    Connolly SJ, Milling TJ Jr, Eikelboom JW, et al. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med. 2016;375(12):1131–41.CrossRefGoogle Scholar
  18. 18.
    Connolly S, Milling T, Eikelboom JW, et al. Andexanet alfa in factor Xa inhibitor-associated acute major bleeding [abstract plus slide presentation]. In: American College of Cardiology’s 67th Annual Scientific Session & Expo (ACC18); 2018.Google Scholar
  19. 19.
    Leeds J, Mandema J, Lu G, et al. Pharmacokinetic/pharmacodynamic modeling of andexanet alfa dose in acute major bleeding [abstract no. 33]. Crit Care Med. 2018;46(1 Suppl):17.CrossRefGoogle Scholar
  20. 20.
    Deitelzweig S, Neuman W, Lingohr-Smith M, et al. Incremental economic burden associated with major bleeding among atrial fibrillation patients treated with factor Xa inhibitors. J Med Econ. 2017;20(12):1217–23.CrossRefGoogle Scholar
  21. 21.
    Heo YA. Andexanet alfa: first global approval. Drugs. 2018;78(10):1049–55.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.SpringerAucklandNew Zealand

Personalised recommendations