Andexant Reversal Guideline

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Guideline for Use of Coagulation Factor Xa (recombinant) Inactivated-zhzo (Andexxa®) for Reversal of the Anticoagulant Effects of Apixaban and Rivaroxaban in Adult Patients

*Andexxa is a restricted medication. Trauma Surgery is not an approving service for Andexxa. If Andexxa is indicated for intracranial bleeding, please contact neurosurgery for approval. For other bleeding, please contact hematology for approval.

  1. Purpose
    1. The purpose of this guideline is to provide recommendations for use of Coagulation Factor Xa (recombinant) Inactivated-zhzo (andexanet; Andexxa) for adult inpatients (18 years of age or older) treated with rivaroxaban (Xarelto) or apixaban (Eliquis) presenting with life threatening or uncontrolled intracranial bleeding.
  2. Criteria for use
    1. Indications:
      1. Rivaroxaban- or apixaban-associated major or life-threatening uncontrolled intracranial bleeding restricted to neurosurgery, stroke team, neurocritical care, or hematology approval
    2. Exclusions:
      1. Appropriately calibrated anti-Xa activity level (apixaban or rivaroxaban) £ 75 ng/mL
      2. Last known apixaban or rivaroxaban dose received > 48 hours prior to presentation. See precautions below for further consideration.
    3. Relative Contraindications:
      1. Acute thrombosis or embolism within the previous 2 weeks should be considered in the risk:benefit discussion when considering use of andexanet. Caution should be taken in light of the thrombotic risks.
    4. Precautions:
      1. Renal function should be considered when determining appropriateness of use beyond 18 hours from last known dose of apixaban or rivaroxaban, as this was used in the clinical trial supporting benefit of andexanet.
        1. If renal function is known and preserved (CrCl > 30 mL/min) consider using 18 hours as the maximum time from last known dose to andexanet administration.
        2. If renal function is unknown or reduced (CrCl < 30 mL/min) may consider administering andexanet up to 48 hours after last known dose due to the potential for prolonged half-life of rivaroxaban and apixaban in this setting, as clinically appropriate.
      2. Significant thrombotic complications were observed in the clinical trial that led to approval of andexanet. Anticoagulation should be resumed as early as deemed clinically appropriate.
  3. Pharmacology
    1. Andexanet is a recombinant, modified human factor Xa decoy protein that binds factor Xa inhibitors, reducing the ability of factor Xa inhibitors to act on endogenous Xa and restoring thrombin generation and normal coagulation.
    2. By the end of the infusion rivaroxaban and apixaban free concentrations were reduced by greater than 90%.
  4. Dosing
    1. The recommended dose is dependent upon the timing, dose, and agent that requires reversal
      1. FXa Inhibitor

        FXa Inhibitor Last Dose

        Timing of FXa Inhibitor Last Dose Before Andexanet Initiation

        < 8 Hours or Unknown

        > 8 Hours


        < 10 mg

        Low Dose


        Low Dose

        >10 mg/unknown

        High Dose


        < 5 mg

        Low Dose

        > 5 mg/unknown

        High Dose

      2. Dose

        Initial IV Bolus

        Follow-on IV Infusion

        Low Dose

        400 mg at a 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

    2. There are no data to support the use of an additional bolus dose or infusion past 2 hours
  5. Storage
    1. Product


      Unopened andexanet alfa vials

      Store refrigerated (2°C to 8°C). DO NOT FREEZE.

      Reconstituted andexanet alfa in vials

      Stable at room temp for up to 8 hrs or up to 24 hrs at 2°C - 8°C

      Reconstituted andexanet alfa in IV bags

      Stable at room temp for up to 8 hrs, or up to 16 hrs at 2°C - 8°C

  6. Administration
    1. Product is supplied as lyophilized powder in single-use vials of 100 mg of andexanet
    2. Administer as an intravenous (IV) bolus followed by infusion
      1. Administration rate of 30 mg/min for bolus dose
      2. Infusion to be continued at ordered rate for maximum 120 minutes
    3. Both bolus and infusion must be administered with a 0.2 or 0.22 micron in-line polyethersulfone or equivalent low protein-binding filter
    4. Flush the line with 25 mL of normal saline after end of infusion to ensure all drug is cleared from the line and administered to the patient
  7. Monitoring
    1. Baseline monitoring
      1. aPTT, platelet count, and hemoglobin/hematocrit
      2. Anti-Xa level of apixaban or rivaroxaban (agent being reversed)
    2. Ongoing monitoring
      1. No specific laboratory monitoring is required
      2. Monitor for resolution of bleed and thrombosis
  8. Use of andexanet with additional supportive therapies
    1. Prothrombin complex concentrate (PCC)
      1. Not routinely recommended as not known to provide any additional benefit
      2. PCC should not be administered within 12 hours of andexanet due to concerns for thrombosis
      3. See PCC Guidelines for Use for additional information
    2. Recombinant activated Factor VII (NovoSeven) (rfVIIa)
      1. Not routinely recommended as not known to provide any additional benefit
      2. Factor VIIa should not be administered within 12 hours of andexanet due to concerns for thrombosis
      3. See Factor VIIa Guidelines for Use for additional information
    3. Refer to Emergent Reversal of Antithrombotic Agents for additional guidance
  9. Drug Interactions
    1. No compatibility studies have been performed; do not mix with other solvents or products

Special Thanks


If reusing this content please use the following information to provide credit to the content authors:  

  1. Title: Andexant Reversal Guideline
  2. Author:  Michigan Medicine
  3. Source:
  4. License: “CC BY-NC 4.0”

Andexant Reversal Guideline,  Michigan Medicine, Dept of Surgery,  “CC BY-NC 4.0”

  1. Andexxa (coagulation factor Xa (recombinant), inactivated-zhzo) prescribing information. Available at:  Accessed August 25, 2021.
  2. Connolly SJ, Milling TJ, Eikelboom JW, et al. Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors. N Engl J Med. 2016;375(12):1131-41.

Last reviewed: 09 June 2021