What is a reversal agent for Eliquis (apixaban)?

Reversal Agent for Eliquis (Apixaban)

Andexanet alfa is the FDA-approved specific reversal agent for apixaban (Eliquis) and should be administered in cases of life-threatening bleeding. 1

Primary Reversal Strategy

• Andexanet alfa is the first-line specific reversal agent for apixaban-associated life-threatening bleeding, with dosing dependent on the timing and last dose of apixaban 2, 1
• Low dose regimen (for last dose ≤5 mg taken ≥8 hours prior or <8 hours prior): 400 mg IV bolus at 30 mg/min followed by 4 mg/min infusion for up to 120 minutes (480 mg total infusion) 2, 1
• High dose regimen (for last dose >5 mg taken <8 hours prior or unknown timing/dose): 800 mg IV bolus at 30 mg/min followed by 8 mg/min infusion for up to 120 minutes (960 mg total infusion) 2, 1
• Andexanet alfa works by binding and sequestering factor Xa inhibitors, rapidly reducing unbound apixaban concentration by 51-89% within 2 minutes of administration 3

Alternative Reversal Options

• If andexanet alfa is unavailable, prothrombin complex concentrate (PCC) or activated PCC (aPCC) at 50 units/kg can be administered as an alternative 2, 4
• A retrospective study showed that aPCC achieved clinical hemostasis in 68.6% of patients with major bleeding associated with apixaban or rivaroxaban 5
• For known recent ingestion of apixaban (within 2-4 hours), activated charcoal can be considered to reduce absorption 2

Indications for Reversal

• Life-threatening bleeding, such as intracranial hemorrhage 1, 4
• Bleeding in critical organs or closed spaces (intraspinal, intraocular, pericardial, pulmonary, retroperitoneal) 1, 4
• Severe bleeding with hemodynamic instability 4
• Need for emergency surgery or urgent invasive procedure with high bleeding risk 6

Laboratory Assessment

• Early assessment of laboratory coagulation tests and direct measurements of apixaban levels is recommended before deciding on reversal 2, 1
• Anti-Xa activity assays are preferred for quantifying apixaban levels, with a threshold of >50 ng/mL considered clinically significant for patients with serious bleeding 2, 1
• Current commercial anti-Xa activity assays are unsuitable for measuring factor Xa activities after andexanet alfa administration 2

Important Considerations and Monitoring

• The duration of andexanet alfa reversal effect is approximately 2 hours after the infusion is stopped 1
• Monitor for thromboembolic events, which occur in approximately 10% of patients receiving andexanet alfa 1, 4
• Apixaban has a half-life of 6-15 hours in patients with normal renal function, which extends to 17 hours in patients with severe renal impairment 2, 7
• Hemodialysis does not appear to have a substantial impact on apixaban exposure, unlike dabigatran which can be removed by hemodialysis 8

Clinical Efficacy

• The ANNEXA-4 study showed that andexanet alfa reduced anti-factor Xa activity by approximately 93% and achieved good or excellent hemostasis in 80% of patients with major bleeding 1
• In patients requiring urgent or emergent procedures, andexanet alfa achieved excellent or good hemostasis in 78.9% of patients within 24 hours after administration 6

Institutional Considerations

• Healthcare systems should develop specific protocols for DOAC reversal to ensure appropriate and timely administration of reversal agents 9
• The decision to use specific reversal agents should consider the severity of bleeding, timing of last dose, renal function, and availability of reversal agents 9, 10