What is the reversal agent for rivaroxaban (Xarelto)?

Reversal Agent for Rivaroxaban (Xarelto)

Andexanet alfa is the specific FDA-approved reversal agent for rivaroxaban and should be administered as an 800 mg IV bolus followed by a 960 mg IV infusion over 2 hours for patients with life-threatening bleeding who have taken rivaroxaban within 7 hours or with unknown timing of last dose. 1, 2

Mechanism of Action and Efficacy

Andexanet alfa is a recombinant modified human factor Xa protein that:

• Acts as a decoy by binding to rivaroxaban with high affinity
• Lacks catalytic activity and cannot participate in coagulation
• Rapidly reduces anti-factor Xa activity by approximately 92% within minutes 1, 3
• Maintains reversal effect during the 2-hour infusion period
• Restores thrombin generation in 96% of patients within 2-5 minutes 3

Dosing Protocol

The dosing regimen depends on the timing of the last rivaroxaban dose:

1. High-dose regimen (for last dose <7 hours or unknown timing):

   • 800 mg IV bolus over 15-30 minutes
   • Followed by 960 mg IV infusion over 2 hours 1, 2

2. Low-dose regimen (for last dose >7 hours):

   • 400 mg IV bolus over 15-30 minutes
   • Followed by 480 mg IV infusion over 2 hours 2

Clinical Evidence

The ANNEXA-4 study demonstrated that:

• Andexanet alfa reduced anti-FXa activity by 92% from baseline in rivaroxaban-treated patients 1
• Effective hemostasis was achieved in approximately 82% of patients at 12 hours 1
• The effect persisted for the duration of the infusion but began to diminish 4 hours after discontinuation 1

Important Considerations and Caveats

• Rebound anticoagulation: Anti-FXa activity may increase after the infusion ends, with levels returning to approximately 39% below baseline 4 hours after infusion 1
• Thrombotic risk: Thrombotic events occurred in 10-18% of patients within 30 days of administration 2, 1
• Monitoring: Standard coagulation tests (PT, INR, aPTT) are not recommended for monitoring the anticoagulant effect of rivaroxaban or its reversal 4
• Timing of restarting anticoagulation: Consider restarting anticoagulation 7-14 days after confirmed hemostasis 2

Alternative Options When Andexanet Alfa is Unavailable

If andexanet alfa is not available, alternative options include:

• Four-factor prothrombin complex concentrate (4F-PCC): 50 U/kg 1, 2
• Activated prothrombin complex concentrate (aPCC): 50 U/kg 2

Special Considerations

• Rivaroxaban has a terminal elimination half-life of 5-9 hours in healthy subjects aged 20-45 years 4
• Hemodialysis is not effective for removing rivaroxaban due to high plasma protein binding 4
• Protamine sulfate and vitamin K are not expected to affect the anticoagulant activity of rivaroxaban 4

Andexanet alfa represents a significant advancement in the management of rivaroxaban-associated bleeding, providing rapid and effective reversal of anticoagulation in emergency situations where time is critical for patient survival.