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Andexanet alfa for the reversal of bleeding with apixaban or rivaroxaban

Authoring team

Andexanet alfa is recommended as an option for reversing anticoagulation from apixaban or rivaroxaban in adults with life-threatening or uncontrolled bleeding, only if (1):

  • the bleed is in the gastrointestinal tract, and
  • the company provides andexanet alfa according to the commercial arrangement

Andexanet alfa

  • an engineered variant of factor Xa, whose similarity to the human form allows it to bind factor Xa inhibitors with high affinity
  • in comparison to factor Xa, which contains serine, andexanet alfa contains alanine as its active-site residue and lacks a membrane-binding domain
    • allows andexanet alfa to successfully bind factor Xa inhibitors without promoting further anticoagulant activity
    • andexanet alfa's procoagulant effects are achieved through the ability to bind and sequester factor Xa inhibitors
    • drug can also bind and inhibit the activity of tissue-factor pathway inhibitor, which can increase thrombin generation and ultimately promote a procoagulant state

Pharmacodynamics

  • administration of an intravenous (IV) bolus dose of andexanet alfa followed by a two-hour continuous IV infusion resulted in a rapid decrease of anti-factor Xa activity
  • initial reduction in anti-factor Xa activity and regeneration of normal thrombin levels occur within two minutes of IV bolus-dose administration
  • reduced anti-factor Xa activity remains for up to two hours following discontinuation of the infusion
  • also andexanet alfa has the ability to inhibit tissue-factor pathway inhibitor, which is maintained for at least 22 hours following andexanet alfa's administration

Reference:

  1. NICE (May 2021). Andexanet alfa for reversing anticoagulation from apixaban or rivaroxaban
  2. Momin JH et al. Andexanet Alfa (Andexxa (R)) for the Reversal of Direct Oral Anticoagulants.PT. 2019 Sep; 44(9): 530-532, 549.

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