*****UW hospitals DO NOT have access to andexanet alfa at this time.*****
Contents
Mechanism of Action
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 alfa may have “off-target” prothrombotic effects, possibly resulting from its effects on Tissue Factor Pathway Inhibitor (TFPI).
Indication
Approved for reversal of the anticoagulant effect rivaroxaban and apixaban in the setting of life-threatening bleeding.
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 alfa. 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
Based on the last dose and timing of rivaroxaban or apixaban there is a Low Dose and High Dose regimen of andexanet alfa.
Andexanet Alfa Dose Based on Rivaroxaban or Apixaban Dose (Timing of FXa Inhibitor Last Dose Before Andexanet Alfa 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 |
Andexanet Alfa Dosing Regimens
| Dose (The safety and efficacy of more than one dose have not been evaluated.) |
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 |
- After reconstitution, andexanet alfa 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 alfa has not been established.
- There are no recommendations for dose adjustments due to renal or hepatic dysfunction.
- Andexanet alfa may have off-target prothrombotic effects; therefore, therapeutic anticoagulation should be restarted as soon as clinically appropriate after treatment with andexanet alfa.
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.
