Andexanet alfa (Andexxa)

*****Andexanet alfa (Andexxa) was NOT ADDED to the UW Medicine formulary at this time due to unclear risk vs benefit and high cost. Providers should continue to order 4F-PCC (Kcentra) for urgent reversal of anti-Xa inhibitors per UW Medicine guidelines.*****


*****Portola pharmaceuticals, maker of andexanet alfa (Andexxa), received approval for their Generation 2 manufacturing process on Dec 31st, 2018. UW hospitals DO NOT have access to andexanet alfa at this time.*****


A recombinant modified human coagulation factor Xa that binds to and sequesters factor Xa inhibitors (such as rivaroxaban and apixaban) to neutralize their anticoagulant effects as measured by anti-Xa activity. Andexanet alpha may have “off-target” prothrombotic effects, possibly resulting from its effects on Tissue Factor Pathway Inhibitor (TFPI).

Approved for reversal of the anticoagulant effect rivaroxaban and apixaban in the setting of:

  • Life-threatening bleeding

Relevant Clinical Trials

Connolly SJ, et al. Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors. N Engl J Med. 2016; 375(12): 1131-1141.

Siegal DM, et al. Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity. N Engl J Med. 2015; 373(25): 2413-2424.

Therapeutic Monitoring

  • Prior to use, assess the patient for recent administration of rivaroxaban or apixaban.
  • Monitor for signs/symptoms of clinically relevant bleeding and thromboembolic events.
  • Andexanet alfa will likely correct anti-Xa values, but the correlation of lab results with improved clinical outcomes has not been established.
  • Anti-Xa activity can rebound after completing the infusion of andexanet. Clinical trials suggest peak anti-Xa activity at 4 hours after infusion, then decrease at a rate similar to clearance of the factor Xa inhibitor.
  • The safety and efficacy of repeated doses of andexanet alfa have not been established.

Dosing and Administration

  • There are two dosing regimens (Low or High dose) of andexanet alfa based on the last dose and timing of rivaroxaban or apixaban.

Table 1: ANDEXXA Dosing Regimes

Dose* Initial IV Bolus Follow-On IV Infusion
Low dose 400 mg at target rate of 30 mg/min 4 mg/min for up to 120 minutes
High dose 800 mg at a target rate of 30 mg/min 8 mg/min for up to 120 minutes

*The safety and efficacy of more than one dose have not been evaluated.

Table 2: ANEXXA Dose Based on Rivaroxaban or Apixaban Dose (Timing of FXa Inhibitor Last Dose Before ANDEXXA Initiation)

FXa Inhibitor FXa Inhibitor Last Dose < 8 Hours or Unknown ≥ 8 Hours
Rivaroxaban ≤ 10 mg Low Dose Low Dose
Rivaroxaban > 10 mg / Unknown High Dose Low Dose
Apixaban ≤ 5 mg Low Dose Low Dose
Apixaban  > 5 mg / Unknown High Dose Low Dose
  • After reconstitution, andexanet must be used within 8 hours at room temperature.
  • Administer through a 0.2-0.22 micron in-line polyethersulfone or equivalent low protein-binding filter.
  • Administer the IV bolus dose at approximately 30 mg/min.
  • Within 2 minutes following the IV bolus, administer the continuous IV infusion for up to 120 minutes.

Drug Interactions

  • There are no known drug interactions

Other Considerations

  • The safety and efficacy of repeat treatment with andexanet has not been established.
  • There are no recommendations for dose adjustments due to renal or hepatic dysfunction.
  • Andexanet may have off-target prothrombotic effects;  therefore, therapeutic anticoagulation should be restarted as soon as clinically appropriate after treatment with andexanet.