Safety of Andexanet Alfa for DOAC Reversal

Efficacy and Mechanism of Action

Andexanet alfa is a recombinant modified human factor Xa variant that acts as a decoy, binding to factor Xa inhibitors with similar affinity as native factor Xa, thereby restoring normal hemostatic function 1
It rapidly reverses anticoagulation with factor Xa inhibitors, decreasing anti-FXa activity by >90% for apixaban and rivaroxaban within minutes of administration 2
The reversal effect is transient, with anti-FXa activity returning to pre-treatment levels approximately two hours after completion of infusion 3

Prompt resumption of anticoagulation after bleeding control significantly reduces thrombotic risk 4, 5

The American College of Cardiology recommends andexanet alfa for life-threatening bleeding, such as intracranial hemorrhage or uncontrollable hemorrhage 2, 6
The American College of Cardiology also recommends andexanet alfa for bleeding in a closed space or critical organ, persistent major bleeding despite local hemostatic measures, need for urgent intervention with high bleeding risk, and emergency surgery in patients at high risk for procedural bleeding 2, 6

Lower doses are needed for apixaban than rivaroxaban due to lower drug concentrations with twice-daily dosing 2, 1
Standard dosing includes a low dose for apixaban ≤5 mg or rivaroxaban ≤10 mg, or when last dose was ≥8 hours prior, and a high dose for apixaban >5 mg or rivaroxaban >10 mg, or when last dose was <8 hours prior 7

Laboratory testing should not delay andexanet administration in life-threatening bleeding situations 2, 8
If andexanet alfa is unavailable, prothrombin complex concentrates or activated PCCs can be considered as alternative hemostatic agents 9, 7
Activated charcoal may be used for known recent ingestion of factor Xa inhibitors 9, 7

Andexanet alfa is effective for reversing the anticoagulant effects of edoxaban and may be considered as a reversal strategy in patients with acute major bleeding, though this use is currently off-label and requires further confirmatory data 10

For edoxaban reversal, the high-dose regimen is recommended: 800 mg bolus followed by a 960 mg infusion (8 mg/min) 11

Andexanet alfa should be considered for edoxaban-treated patients with bleeding in a closed space or critical organ (intraspinal, intraocular, pericardial, pulmonary, retroperitoneal) 12
Andexanet alfa should be considered for edoxaban-treated patients with persistent major bleeding despite local hemostatic measures 12
If andexanet alfa is unavailable or not approved for edoxaban in your region, prothrombin complex concentrates (PCCs) at 25-50 U/kg may be initiated 10
An initial dose of 25 U/kg PCC is suggested, as this dose has been shown to provide effective hemostasis without increased rates of thromboembolic events 10

Plasma levels of antifactor Xa agents following andexanet alfa administration cannot be reliably measured with standard anti-Xa assays due to dissociation of andexanet alfa from the anticoagulant during dilution 10
Co-administration of tranexamic acid (15 mg/kg or 1 g) is indicated in trauma patients independent of the present DOAC and reversal strategy 10