Andexanet alfa

Created 25/01/2022, last revision 01/10/2022

  • until recently, prothrombin complex concentrates (PCCs) were used off-label for the acute life-threatening bleeding secondary to factor Xa (FXa) inhibitors
  • in 2018, the FDA approved andexanet alfa (ONDEXXYA, ANDEXXA) for the reversal of life-threatening hemorrhages in patients anticoagulated with FXa inhibitors (apixaban/rivaroxaban)  → more
    • a modified recombinant inactive form of human FXa, which specifically binds to FXa inhibitor molecules and causes their sequestration, thereby rapidly reducing their activity
    • positive trials:  ANNEXA-A, ANNEXA-R, and ANNEXA-4  [Medscape 2016]
    • administered as a bolus over 15-30 minutes, followed by a 2-hour infusion
  • new guidelines now recommend the use of andexanet alfa as the first-line therapy
  • ANNEXA-4 was a multicenter, prospective, open-label, single-arm trial that evaluated patients with major bleeding; the trial was published in 2019
  • n = 352
  • all patients received a bolus of andexanet alfa followed by a 2h infusion to treat major acute bleeding arising after taking a factor Xa inhibitor in the previous 18 h
    • ICH 64%, GIT bleeding 26%
    • rivaroxaban 36%, apixaban 55%, edoxaban 3%, enoxaparin 6% (only those with dose > 1 mg/kg)
  • the study evaluated the decrease in anti-Xa activity and hemostatic efficacy after 12h from the end of infusion
    • apixaban and rivaroxaban showed a 92% decrease in mean anti-Xa activity; enoxaparin showed a 75% decrease
    • hemostasis at 12 h was rated as excellent/good in 82% of patients
  • mortality/30 days: 14%, thrombotic events: 10%, two patients had a mild reaction after infusion

Standard dose

  • ≥ 8h from DOAC administration
  • < 8h after administration of rivaroxaban ≤ 10 mg or apixaban ≤ 5mg
  • IV bolus 400mg at a rate of 30 mg/min (approx. 13 min)
  • followed by infusion at a rate of 4 mg/min for 120 min (total dose = 480 mg)

Higher dose

  • unclear time of last DOAC administration
  • < 8h after administration of rivaroxaban > 10mg or apixaban > 5mg
  • IV bolus 800mg at a rate of 30 mg/min (approx. 13 min)
  • followed by infusion at a rate of 8 mg/min for 120 min (total dose = 960 mg)
  • during and after application, actively monitor for any signs of thromboembolic complications !!
  • take care of possible rebound phenomenon   Anti-Xa activity following andexanet administration
Andexanet dose regimens
Andexanet - standard and high dose criteria
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Andexanet alfa