Can Balfaxar (andexanet alfa) reverse Eliquis (apixaban) in patients with a history of atrial fibrillation, deep vein thrombosis, or pulmonary embolism?

Can Andexanet Alfa (Balfaxar) Reverse Apixaban (Eliquis)?

Yes, andexanet alfa (Balfaxar) can effectively reverse apixaban (Eliquis) in patients with life-threatening or uncontrolled bleeding, with FDA approval specifically for this indication. 1

FDA-Approved Indication and Mechanism

• Andexanet alfa is FDA-approved for reversal of apixaban and rivaroxaban in patients presenting with life-threatening or uncontrolled bleeding 1
• The drug works as a recombinant modified factor Xa molecule that competitively binds to factor Xa inhibitors, rapidly neutralizing their anticoagulant effect 2

Dosing Protocol for Apixaban Reversal

For apixaban reversal, use the low-dose regimen: 2, 1

• 400 mg IV bolus administered at 30 mg/min over approximately 15 minutes
• Followed by 480 mg continuous infusion at 4 mg/min for 120 minutes (2 hours)

This dosing applies regardless of timing since last apixaban dose 2

Efficacy Data

• In the ANNEXA-4 trial, andexanet alfa reduced median anti-factor Xa activity by 93% in apixaban-treated patients within minutes of administration 2
• Among apixaban patients with baseline anti-Xa activity >150 ng/mL, 68% achieved >90% reduction from baseline after andexanet administration 1
• Excellent or good hemostasis at 12 hours was achieved in 79% of patients with major bleeding across all factor Xa inhibitors 2

Clinical Context and Patient Populations

The evidence supports andexanet alfa use in patients with: 1

• Intracranial hemorrhage (64% of ANNEXA-4 patients)
• Gastrointestinal bleeding (26% of patients)
• Other critical site bleeding (10% of patients)

Most patients in clinical trials had atrial fibrillation (81%) or venous thromboembolism (25%) as their indication for anticoagulation 1

Critical Safety Considerations

Thrombotic Risk

• 18% of patients experienced thrombotic events within 30 days after andexanet administration, including stroke (25% of thrombotic events), DVT (25%), MI (16%), and PE (8%) 1
• The median time to thrombotic event was 7 days, with 33% occurring within the first 3 days 1
• Among patients who resumed anticoagulation within 30 days, 8% experienced thrombotic events 1

Re-elevation of Anti-Xa Activity

• Anti-Xa activity returns to approximately 50% of baseline levels within 2 hours after completing the infusion 2, 1
• This rebound effect necessitates continued clinical and laboratory monitoring after andexanet administration 2

Mortality

• 15% mortality rate at 30 days in the ANNEXA-4 study, with 37% of deaths occurring within 10 days 1
• Most deaths occurred in patients with intracranial hemorrhage (69%) 1

Guideline Recommendations

The 2023 ACC/AHA/ACCP/HRS guidelines give andexanet alfa a Class IIa recommendation (reasonable to use) for reversal of apixaban-associated critical site or life-threatening major bleeding 2

The 2019 AHA/ACC/HRS Focused Update provides a Class IIa, Level of Evidence B-NR recommendation for andexanet alfa in rivaroxaban or apixaban-associated life-threatening bleeding 2

Alternative Reversal Strategies

If andexanet alfa is unavailable: 2

• 4-factor prothrombin complex concentrate (4F-PCC) at 50 U/kg (maximum 5000 units) is reasonable
• Activated PCC (aPCC) at 50 U/kg (maximum 2500 units) may be considered
• However, evidence supporting PCC use is limited to animal studies and healthy volunteer data showing only modest correction of coagulation parameters 2

Important Caveats

Heparin Interaction

• Andexanet alfa may interfere with heparin's anticoagulant effect and cause unresponsiveness to heparin 1
• Avoid using andexanet before planned heparinization; if anticoagulation is needed post-reversal, use an alternative to heparin 1

Timing Considerations

• Andexanet should be used in patients who took apixaban within 18 hours of presentation with major bleeding 1, 3
• The drug can be administered immediately without waiting for laboratory confirmation of therapeutic anticoagulation levels in life-threatening bleeding scenarios 2

Resumption of Anticoagulation

• Timing of anticoagulation resumption must balance thrombotic risk against bleeding risk 2, 1
• The 2020 ACC Expert Consensus does not provide specific timing recommendations, but notes that most thrombotic events occurred in patients who did not resume anticoagulation 2

Storage Requirements

• Andexanet alfa requires refrigerated storage, which may limit immediate availability in some clinical settings 2

Common Pitfalls to Avoid

• Do not use andexanet alfa for minor or non-life-threatening bleeding - the vast majority of bleeds can be managed with temporary discontinuation and supportive measures 2
• Do not assume complete sustained reversal - monitor for rebound anticoagulant activity after the 2-hour infusion ends 2, 1
• Do not reflexively avoid resuming anticoagulation - failure to restart anticoagulation contributed to thrombotic events in clinical trials 2, 1
• Do not use standard coagulation tests (INR, aPTT) to guide therapy - these are unreliable for monitoring apixaban levels 2