andexanet alfa for the reversal of bleeding with apixaban or rivaroxaban
Last edited 05/2021 and last reviewed 12/2021
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
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