What is the recommended reversal agent for Eliquis (apixaban) in cases of life-threatening bleeding?

Reversal of Eliquis (Apixaban) in Life-Threatening Bleeding

For life-threatening bleeding in patients taking apixaban (Eliquis), andexanet alfa is the recommended specific reversal agent. 1

First-Line Reversal Strategy

• Andexanet alfa is FDA-approved specifically for reversal of apixaban when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding 2
• Dosing regimen depends on the last dose of apixaban and timing of the last dose: 1, 2
  • Low dose: 400 mg IV bolus over 15 minutes followed by a continuous infusion of 480 mg over 2 hours
  • High dose: 800 mg IV bolus over 30 minutes followed by a continuous infusion of 960 mg over 2 hours

Indications for Reversal

Reversal should be considered in the following scenarios: 1

• Life-threatening bleeding (intracranial hemorrhage, expanding or uncontrollable hemorrhage)
• Bleeding in a critical organ or closed space (intraspinal, intraocular, pericardial, pulmonary, retroperitoneal)
• Persistent major bleeding despite local hemostatic measures
• Risk of recurrent bleeding due to delayed clearance or overdose of apixaban

Laboratory Assessment

• Early assessment of laboratory coagulation tests and direct measurements of DOAC levels (if available) is recommended 1
• Anti-Xa activity assays are preferred for quantifying apixaban levels 1
• A threshold of >50 ng/mL is generally considered clinically significant for patients with serious bleeding 1
• However, in life-threatening situations, do not delay administration of andexanet alfa while waiting for laboratory results 1

Alternative Options When Andexanet Alfa is Unavailable

If andexanet alfa is not available, four-factor prothrombin complex concentrates (4F-PCCs) may be administered: 1

• Recommended dose: 2000 units of 4F-PCC 1
• This is considered a second-line option and is not FDA-approved for this indication 1

Monitoring After Reversal

• Monitor for thromboembolic events, which occur in approximately 10% of patients receiving andexanet alfa 1
• Consider restarting anticoagulation when medically appropriate, as most thrombotic events occur in patients whose baseline anticoagulation is not restarted 1, 2
• The duration of andexanet alfa reversal effect is approximately 2 hours after the infusion is stopped 1

Important Considerations and Caveats

• Andexanet alfa was approved under accelerated approval based on change in anti-FXa activity in healthy volunteers, not on clinical outcomes in patients 2
• The ANNEXA-4 study showed that andexanet alfa reduced anti-FXa activity by approximately 93% and achieved good or excellent hemostasis in 80% of patients 1
• Thrombotic events are a serious concern, occurring in approximately 10% of patients receiving andexanet alfa 1
• The high cost and limited availability of andexanet alfa may be practical barriers in some clinical settings 3

Special Situations

• For patients requiring urgent surgery, andexanet alfa may be considered, though this is not an FDA-approved indication 1, 4
• In cases requiring prolonged procedures, modifications to the standard infusion protocol may be necessary, though data on this approach is limited 4

Remember that the decision to administer reversal agents should be based on the severity of bleeding, patient characteristics, and the availability of specific reversal agents, with the primary goal of reducing morbidity and mortality.