How do you reverse Xarelto (rivaroxaban) in a patient with significant bleeding or needing urgent surgery?

Reversal of Xarelto (Rivaroxaban)

For life-threatening bleeding or urgent high-risk surgery in patients on Xarelto, administer andexanet alfa as the FDA-approved specific reversal agent, using dose-adjusted regimens based on timing and dose of the last rivaroxaban intake. 1

First-Line Reversal Agent: Andexanet Alfa

Andexanet alfa is the only FDA-approved specific reversal agent for rivaroxaban and should be administered immediately without waiting for laboratory confirmation in life-threatening scenarios. 1, 2, 3

Mechanism and Efficacy

• Andexanet alfa is a recombinant modified human factor Xa protein that acts as a decoy, binding and sequestering rivaroxaban with high affinity. 2
• It decreases anti-factor Xa activity by >90% within 2 minutes of administration. 1, 2
• The reversal effect is transient, with anti-factor Xa activity returning toward baseline approximately 2 hours after completing the infusion. 2, 3

Dosing Regimens

Low-dose regimen: 1

• Indication: Rivaroxaban ≤10 mg OR last dose taken ≥8 hours prior
• Administration: 400 mg IV bolus at 30 mg/min, followed by 4 mg/min infusion for up to 120 minutes

High-dose regimen: 1

• Indication: Rivaroxaban >10 mg OR last dose taken <8 hours prior OR timing unknown
• Administration: 800 mg IV bolus at 30 mg/min, followed by 8 mg/min infusion for up to 120 minutes

Specific Indications for Andexanet Alfa

Absolute indications (do not delay): 1, 2

• Life-threatening bleeding: intracranial hemorrhage, symptomatic or expanding extradural hemorrhage, uncontrollable hemorrhage
• Bleeding in closed space or critical organ: intraspinal, intraocular, pericardial, pulmonary, retroperitoneal, or intramuscular with compartment syndrome
• Persistent major bleeding despite local hemostatic measures
• Emergency surgery with high bleeding risk: neurosurgery (intracranial, extradural, spinal), cardiac/vascular surgery (aortic dissection/aneurysm repair), major organ surgery

Situations where reversal is NOT needed: 1

• Elective surgery (can delay ≥24 hours in patients with normal renal function)
• Gastrointestinal bleeding responding to supportive measures
• High drug levels without associated bleeding
• Minor bleeding controlled with local hemostatic measures

Alternative Reversal Strategies (If Andexanet Unavailable)

Four-factor prothrombin complex concentrate (4F-PCC) is the second-line option when andexanet alfa is unavailable, though it lacks FDA approval for rivaroxaban reversal and is less effective. 2, 3

4F-PCC Dosing for Rivaroxaban Reversal

• Dose: 50 units/kg IV (off-label use for factor Xa inhibitors) 1, 3
• Onset: Within 10 minutes 1
• Duration: Approximately 8 hours 1
• Important caveat: Not FDA-approved for factor Xa inhibitor reversal; primarily indicated for warfarin reversal 1

Activated PCC

• May be considered as an alternative hemostatic agent if both andexanet and 4F-PCC are unavailable 2
• Dose for rivaroxaban: 50 units/kg (up to 2500 units) once 1
• Onset: Within 30 minutes 1

Critical Management Considerations

Laboratory Testing

Do not delay andexanet administration waiting for coagulation test results in life-threatening bleeding. 1, 2 Standard anti-factor Xa assays cannot reliably measure plasma levels after andexanet administration due to dissociation during dilution. 2

When drug levels are available: 1

• Drug concentration >50 ng/mL warrants antidote administration in serious bleeding
• Drug concentration >30 ng/mL should prompt reversal consideration for urgent high-risk procedures

Renal Function Impact

Assess creatinine clearance to estimate rivaroxaban half-life: 1

• CrCl >60 mL/min: Half-life ≤12 hours; reversal unlikely needed if last dose >24 hours prior
• CrCl <30 mL/min: Prolonged half-life; delayed clearance may indicate need for reversal even with ongoing bleeding

Thrombotic Risk Management

Thrombotic events occur in 10-18% of patients within 30 days after andexanet administration. 3 Prompt resumption of anticoagulation after achieving hemostatic control significantly reduces this risk. 2

Agents That Do NOT Reverse Rivaroxaban

The following should NOT be used for rivaroxaban reversal: 4, 5

• Vitamin K (ineffective for DOACs)
• Fresh frozen plasma (ineffective)
• Protamine sulfate (ineffective)
• Hemodialysis (rivaroxaban is not dialyzable due to high protein binding) 4

Adjunctive Measures

Activated charcoal: May reduce absorption if rivaroxaban ingestion occurred within 2-3 hours and patient can safely receive oral agents. 2

Tranexamic acid: 15 mg/kg or 1 g IV should be co-administered in trauma patients independent of reversal strategy. 2

Local hemostatic control and adequate fluid resuscitation are equally important as choosing the optimal reversal agent. 6

Storage and Preparation Logistics

• Andexanet alfa requires refrigeration and is supplied in vials requiring mixing (current formulation). 1
• Most frequently administered in emergency department or intensive care unit. 1
• Time-consuming preparation may delay administration; institutional protocols should address rapid availability. 1