Andexanet alfa

Created 25/01/2022, last revision 14/08/2023

  • until recently, prothrombin complex concentrates (PCCs) were used off-label for 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 bleeding in patients anticoagulated with FXa inhibitors (apixaban/rivaroxaban)  → more here
    • a modified recombinant inactive form of human FXa, that specifically binds to and sequesters FXa inhibitor molecules, 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 first-line therapy
  • ANNEXA-4 was a multicenter, prospective, open-label, single-arm trial evaluating patients with major bleeding
  • the trial was published in 2019
  • n = 352
  • all patients received a bolus of andexanet alfa followed by a 2-hour infusion to treat acute major bleeding after taking a factor Xa inhibitor in the previous 18 hours
    • ICH 64%, GIT bleeding 26%
    • rivaroxaban 36%, apixaban 55%, edoxaban 3%, enoxaparin 6% (only those at doses > 1 mg/kg)
  • the study evaluated the decrease in anti-Xa activity and hemostatic efficacy 12 hours after the end of the infusion
    • apixaban and rivaroxaban showed a 92% decrease in mean anti-Xa activity; enoxaparin showed a 75% decrease
    • hemostasis at 12 hours was rated as excellent/good in 82% of patients
  •  30-day mortality 14%, thrombotic events 10%, two patients had a mild post-infusion reaction

Standard dose

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

Higher dose

  • uncertain dose or time of the last DOAC administration
  • < 8h after administration of rivaroxaban > 10mg or apixaban > 5mg
  • IV bolus of 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)
  • actively monitor for signs of thromboembolic complications during and after the infusion
  • consider possible rebound phenomenon   Anti-Xa activity following andexanet administration
Andexanet dose regimens
Andexanet - standard and high dose criteria

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Andexanet alfa