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

≥ 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)

actively monitor for signs of thromboembolic complications during and after the infusion
consider possible rebound phenomenon