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andexanet

Indications: - antidote to factor-Xa inhibitors apixaban, edoxaban, & rivaroxaban - decreases hematoma expansion in factor-Xa inhibitor-associated intracerebral hemorrhage [5]* * thrombotic events including ischemic stroke were increased, - 30-day functional outcomes were unchanged [5] Dosage: - 400 mg IV bolus, followed by 2 hour infusion * FDA notes uncertainties about dose & which patients would benefit [6] Pharmacokinetics: - >90% decline in anti-Xa activity of either apixaban or rivaroxaban within 2-5 minutes after 400 mg IV of andexanet - at 12 hours after infusion, 82% of patients with good or excellent hemostasis [4] Adverse effects: - infusion-associated urticaria - thrombosis within 39 days 10% [4] Mechanism of action: - recombinant modified human factor Xa decoy protein - reverses inhibition of factor Xa by factor Xa inhibitors [2]

General

antidote

References

  1. Siegal DM, Curnutte JT, Connolly SJ et al. Andexanet alfa for the reversal of factor Xa inhibitor activity. N Engl J Med 2015 Nov 11 PMID: 26559317 Free full text - Connors JM. Antidote for factor Xa anticoagulants. N Engl J Med 2015 Nov 11 PMID: 26559124 Free full text
  2. Connolly SJ, Milling TJ, Eikelboom JW et al. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med 2016 Aug 30 PMID: 27573206 http://www.nejm.org/doi/10.1056/NEJMoa1607887
  3. Susman E Novel Drug Reverses Anticoagulation in Emergencies. Andexanet stops 90% of action of factor Xa inhibitors. MedPage Today. March 13, 2018 https://www.medpagetoday.com/meetingcoverage/acc/71736 - Connolly S, et al Report on the ANNEXA-4 study: Andexanet for reversal of anticoagulation in factor Xa-associated acute major bleeding. American College of Cardiology (ACC) 2018; Abstract 409-14
  4. Connolly SJ, Crowther M, Eikelboom JW et al Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors. N Engl J Med. Feb 7, 2019 PMID: 30730782 https://www.nejm.org/doi/full/10.1056/NEJMoa1814051
  5. Connolly SJ et al. Andexanet for factor Xa inhibitor-associated acute intracerebral hemorrhage. N Engl J Med 2024 May 16/23; 390:1745 https://www.nejm.org/doi/10.1056/NEJMoa2313040 - Smith WS, Hemphill JC. Reversing oral anticoagulation in intracerebral hemorrhage. N Engl J Med 2024 May 16/23; 390:1815 https://www.nejm.org/doi/10.1056/NEJMe2403726
  6. Lou N Lack of Clinical Benefit of Andexanet Flummoxes FDA Panel. Yet advisors were not inclined to take back approval for bleeding reversal agent. MedPage Today. November 21, 2024 https://www.medpagetoday.com/cardiology/strokes/113053