From the Guidelines
Andexanet alfa is the recommended method for reversing apixaban in cases of life-threatening or uncontrolled bleeding. The standard dosing regimen consists of an initial IV bolus followed by a 2-hour infusion. For patients on apixaban, the recommended dose is 400 mg IV bolus at a rate of 30 mg/minute, followed by a continuous infusion of 4 mg/minute for 120 minutes (480 mg total) 1. For patients who took their last dose of apixaban more than 8 hours prior or if the timing is unknown, a lower dose may be considered. Andexanet alfa works as a recombinant modified factor Xa protein that acts as a decoy, binding to apixaban and preventing it from inhibiting native factor Xa, thus restoring normal hemostasis.
In emergency situations where andexanet alfa is unavailable, prothrombin complex concentrate (PCC) at 25-50 units/kg may be used as an alternative, though it is less specific and has less evidence supporting its use 1. Supportive measures including local hemostatic measures, fluid resuscitation, blood product transfusion, and identifying the bleeding source should be implemented concurrently with reversal agents. Renal function should be monitored as apixaban is partially cleared by the kidneys.
The use of andexanet alfa has been studied in several trials, including the ANNEXA-4 trial, which demonstrated its efficacy in reversing apixaban and rivaroxaban in patients with major bleeding 1. The trial showed that andexanet alfa decreased the median anti-FXa activity by 92% for both apixaban and rivaroxaban, with excellent or good hemostasis 12 hours after infusion.
Key points to consider when using andexanet alfa for apixaban reversal include:
- The dosing regimen: 400 mg IV bolus followed by a 2-hour infusion of 4 mg/minute
- The timing of the last dose of apixaban: a lower dose may be considered if the last dose was taken more than 8 hours prior or if the timing is unknown
- The use of alternative reversal agents: PCC at 25-50 units/kg may be used if andexanet alfa is unavailable
- The importance of supportive measures: local hemostatic measures, fluid resuscitation, blood product transfusion, and identifying the bleeding source should be implemented concurrently with reversal agents
- The need to monitor renal function: apixaban is partially cleared by the kidneys, and renal function should be monitored during treatment.
From the FDA Drug Label
An agent to reverse the anti-factor Xa activity of apixaban is available The pharmacodynamic effect of apixaban tablets can be expected to persist for at least 24 hours after the last dose, i.e., for about two drug half-lives. Prothrombin complex concentrate (PCC), activated prothrombin complex concentrate or recombinant factor VIIa may be considered, but have not been evaluated in clinical studies [see Clinical Pharmacology (12. 2)]. Activated oral charcoal reduces absorption of apixaban, thereby lowering apixaban plasma concentration
The recommended method for reversing Apixaban in cases of life-threatening or uncontrolled bleeding is to use an agent that reverses anti-factor Xa activity. Options include:
- Prothrombin complex concentrate (PCC)
- Activated prothrombin complex concentrate
- Recombinant factor VIIa
- Activated oral charcoal to reduce absorption of apixaban However, these options have not been evaluated in clinical studies 2.
From the Research
Apixaban Reversal Methods
The recommended method for reversing Apixaban in cases of life-threatening or uncontrolled bleeding is through the use of Andexanet Alfa. This is supported by several studies, including 3, 4, 5, 6, and 7.
Mechanism of Action
Andexanet Alfa works by acting as a decoy, competing with endogenous factor Xa to bind factor Xa inhibitors, thereby reversing the anticoagulant effects of factor Xa inhibitors and restoring the activity of endogenous factor Xa 4.
Efficacy and Safety
Studies have shown that Andexanet Alfa is effective in reducing anti-factor Xa levels and achieving excellent or good hemostasis in patients with acute major bleeding on Apixaban or Rivaroxaban 3, 5. However, it is also associated with a risk of thrombotic events, and anticoagulant therapy should be resumed as soon as medically appropriate 4, 7.
Administration
Andexanet Alfa is administered as a bolus followed by a continuous infusion, with the goal of rapidly and sustainably reversing anticoagulation 5, 7. The dosing regimen may vary depending on the specific clinical scenario, and the need for baseline anti-Xa inhibitor levels measured by point-of-care testing is still being explored 6.
Key Points
- Andexanet Alfa is a specific reversal agent for factor Xa inhibitors, including Apixaban
- It works by competing with endogenous factor Xa to bind factor Xa inhibitors, reversing anticoagulation
- Effective in reducing anti-factor Xa levels and achieving excellent or good hemostasis
- Associated with a risk of thrombotic events, and anticoagulant therapy should be resumed as soon as medically appropriate
- Administration is typically as a bolus followed by a continuous infusion, with dosing regimen varying depending on clinical scenario