Andexanet alfa for the reversal of bleeding with apixaban or rivaroxaban

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.