What is the antidote for Rivaroxaban (Xarelto)?

Antidote for Rivaroxaban

Andexanet alfa is the specific reversal agent for rivaroxaban and should be administered for life-threatening or uncontrolled bleeding. 1, 2, 3

Mechanism and Efficacy

Andexanet alfa is a recombinant modified human factor Xa molecule that acts as a decoy, binding rivaroxaban with similar affinity as native factor Xa, thereby reversing its anticoagulant effect. 1, 2

• Reversal is rapid and substantial: Andexanet alfa reduces anti-factor Xa activity by approximately 89% within minutes of administration in rivaroxaban-treated patients. 1
• The effect is transient: Anti-factor Xa activity returns toward baseline approximately 2 hours after completion of the infusion, with a relative decrease from baseline of only 39% at 4 hours post-infusion. 1

Dosing Regimen

The dose depends on the rivaroxaban dose and timing of the last dose: 2, 4

• Low dose: 400 mg IV bolus over 15 minutes, followed by 480 mg continuous infusion over 2 hours

  • Use for rivaroxaban ≤10 mg OR when last dose was ≥8 hours prior 2

• High dose: 800 mg IV bolus over 30 minutes, followed by 960 mg continuous infusion over 2 hours

  • Use for rivaroxaban >10 mg OR when last dose was <8 hours prior 2

Clinical Indications

Andexanet alfa is recommended by the American College of Cardiology for: 2

• Life-threatening bleeding (intracranial hemorrhage, uncontrollable hemorrhage) 2
• Bleeding in a closed space or critical organ (intraspinal, intraocular, pericardial, pulmonary, retroperitoneal) 2
• Persistent major bleeding despite local hemostatic measures 2
• Need for urgent intervention with high bleeding risk 2
• Emergency surgery in patients at high risk for procedural bleeding 2

Critical Safety Considerations

Thrombotic events occur in approximately 10-18% of patients within 30 days following andexanet alfa administration. 1, 4

• Anticoagulation must be resumed promptly after bleeding control to significantly reduce thrombotic risk. 2
• The decision to resume anticoagulation should balance bleeding severity against thrombotic risk, but delay increases thrombotic complications. 2

Practical Implementation

• Do not delay administration for laboratory testing in life-threatening bleeding situations. 2
• Laboratory coagulation tests are not reliable for monitoring andexanet alfa effect, as plasma anti-Xa levels cannot be accurately measured after andexanet administration due to drug dissociation during dilution. 2
• Hemostasis was achieved in approximately 79-80% of patients in the ANNEXA-4 study. 1, 4

Alternative Options When Andexanet Alfa is Unavailable

If andexanet alfa is not available: 1, 2

• Four-factor prothrombin complex concentrates (4F-PCCs) at 25-50 U/kg may be used 2
• An initial dose of 25 U/kg PCC is suggested, as this provides effective hemostasis without increased thromboembolic events 2
• Activated prothrombin complex concentrates or recombinant factor VIIa are additional alternatives 1

Additional Supportive Measures

• Activated charcoal may be considered for known recent ingestion of rivaroxaban. 2
• Hemodialysis is not effective for rivaroxaban removal due to high plasma protein binding (>90%). 3