II. Background
- Released 2018 in U.S.
III. Mechanism
- Andexxa is a Inactivated Recombinant Factor Xa decoy Protein that binds Factor Xa Inhibitors
- Factor Xa Inhibitors are not irreversibly bound, and rebound bleeding may occur after infusion
- Antidote studied for Eliquis (Apixaban) or Xarelto (Rivaroxaban)
- Thought to be effective for other Factor Xa Inhibitors (Edoxaban, Betrixaban)
IV. Dosing
- Low Dose: 400 mg IV bolus (at 30 mg/min), followed by infusion at 4 mg/min for 2 hours
- Indicated if last DOAC dose >8 hours ago, or if high dose criteria not met
- High Dose: 800 mg IV bolus (at 30 mg/min), followed by infusion at 8 mg/min for 2 hours
- Indicated for Apixaban >5 mg/dose, Rivaroxaban 10 mg/dose or unknown dose
V. Efficacy
- Limits progression of bleeding within 12 hours of dose (onset as early as 1 hour)
- Excellent or good Hemostasis in 82% of patients in ANNEXa-4 study
- Ineffective in the 25% of patients who have low anti-Factor Xa Inhibitor
VI. Adverse Effects
- Expensive: $25,000 to 50,000 per patient
- Infusion site reaction (10%)
- Risk of Hypercoagulability complications (CVA, VTE, MI)
- FDA black box warning
- Thrombosis risk at 30 days: 10% (contrast with 3 to 8% with PCC4)
- Deep Vein Thrombosis (6%)
- Ischemic Cerebrovascular Accident (5%)
- Infections
- Urinary Tract Infection (5%)
- Pneumonia (5%)
- Rebound bleeding (return of Xa activity)
- Repeat bleeding may occur after initially controlled following Andexanet Alfa
- Avoid repeating Andexanet Alfa
- Consider Prothrombin Complex Concentrate (PCC4)
VII. Resources
- Andexanet Alfa (DailyMed)
VIII. References
- (2018) Presc Lett 25(7): 37-8
- Cook and Mishler (2018) Crit Dec Emerg Med 32(8): 32
- Ebersole, Toomey and Baugh (2021) Crit Dec Emerg Med 35(5): 3-9
- Connolly (2019) N Engl J Med 380(14):1326-35 +PMID:30730782 [PubMed]