What is the recommended reversal agent for Xarelto (Rivaroxaban)?

Reversal of Rivaroxaban (Xarelto) Anticoagulation

Andexanet alfa is the recommended specific reversal agent for life-threatening or uncontrolled bleeding in patients taking rivaroxaban (Xarelto). 1

First-Line Reversal Options

Specific Reversal Agent

• Andexanet alfa should be administered as an intravenous bolus of 800 mg over 30 minutes followed by a continuous infusion of 960 mg over 2 hours (high dose) for rivaroxaban reversal 1
• This dosing regimen is specifically designed for rivaroxaban, which requires the higher dose protocol compared to apixaban 1
• Andexanet alfa works by acting as a decoy protein that binds to factor Xa inhibitors with similar affinity as native factor Xa, thereby removing the anticoagulant from circulation 1

Alternative Options When Andexanet Alfa is Unavailable

• Four-factor prothrombin complex concentrate (4F-PCC) at a dose of 2000 units may be administered if andexanet alfa is not available 1
• However, it's important to note that PCCs do not consistently reverse laboratory markers of rivaroxaban anticoagulation and have shown variable results in clinical studies 1

When to Use Reversal Agents

Reversal agents should be used selectively in the following scenarios:

• Life-threatening bleeding that is uncontrolled 1
• Bleeding into critical organs (central nervous system, abdominal, thoracic) 1
• Hemorrhagic shock not responding to resuscitation 1
• Need for urgent surgical or invasive procedures with high bleeding risk 1

Laboratory Assessment

• Early assessment of coagulation tests and direct measurements of rivaroxaban levels (if available) is recommended before deciding on reversal 1
• This helps confirm the presence of therapeutic anticoagulation and guides the decision for reversal 1
• Anti-Xa activity assays are the most accurate way to measure rivaroxaban levels when available 1

Clinical Considerations

Timing of Administration

• Andexanet alfa has a rapid onset of action (within 2 minutes) but a relatively short half-life (approximately 6 hours) 1
• After administration, monitoring for recurrent anticoagulation effect is important, especially in patients with ongoing risk factors for bleeding 1

Thrombotic Risk

• There is a risk of thrombotic events following reversal (reported at approximately 4.8% within 30 days) 1
• Consider restarting anticoagulation once hemostasis is achieved and it is safe to do so, particularly in patients with high thrombotic risk 1, 2

Emerging Agents

• Ciraparantag (PER977) is a synthetic water-soluble molecule in development that may reverse multiple anticoagulants including rivaroxaban, but is not yet approved 1

Practical Approach to Rivaroxaban Reversal

1. Confirm rivaroxaban use and assess bleeding severity
2. For life-threatening or critical organ bleeding:
   • Administer andexanet alfa (preferred) 1
   • Use 4F-PCC if andexanet alfa is unavailable 1
3. For non-life-threatening bleeding:
   • Consider temporary discontinuation of rivaroxaban and supportive measures 1
4. Monitor for hemostasis and potential thrombotic complications 1
5. Plan for appropriate timing of anticoagulation resumption 2

Remember that the vast majority of bleeds can be managed conservatively with temporary discontinuation of rivaroxaban and supportive measures. Specific reversal agents should be reserved for severe and life-threatening bleeding scenarios 1.