From the Guidelines
Eliquis (apixaban) can be reversed in emergency situations using Andexxa (andexanet alfa), which is specifically designed to reverse factor Xa inhibitors like Eliquis. Andexxa works by binding to the anticoagulant and preventing it from inhibiting factor Xa, thus restoring normal blood clotting. For life-threatening bleeding, Andexxa is administered as an IV bolus over 15-30 minutes, followed by a 2-hour infusion, with dosing based on the patient's last Eliquis dose and timing, as recommended by the 2023 ACC/AHA/ACCp/HRS guideline for the diagnosis and management of atrial fibrillation 1. The dosing of Andexanet alfa is determined by the last dose of apixaban and the timing of the dose, with a low-dose regimen consisting of a 400-mg bolus followed by a 4 mg/min infusion for up to 120 minutes, and a high-dose regimen consisting of an 800-mg bolus followed by an 8 mg/min infusion for up to 120 minutes, as outlined in the 2020 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants 1. In settings where Andexxa is unavailable, prothrombin complex concentrate (PCC) at 25-50 units/kg may be used as an alternative, though it's less specific, as suggested by the European guideline on management of major bleeding and coagulopathy following trauma: sixth edition 1. For non-emergency situations, simply stopping Eliquis is often sufficient since it has a relatively short half-life of 12 hours. Supportive measures like mechanical compression, surgical intervention, fluid replacement, and blood product transfusion may also be necessary depending on the bleeding severity. Activated charcoal can be considered if Eliquis was ingested within 2-6 hours to reduce absorption. It is essential to note that the use of Andexanet alfa may interfere with the anticoagulation effect of heparin, and coagulation parameters do not correlate with the drug's efficacy, as mentioned in the 2023 ACC/AHA/ACCp/HRS guideline for the diagnosis and management of atrial fibrillation 1. Additionally, the 2023 WSES guidelines on the management of trauma in elderly and frail patients recommend the administration of Andexanet alfa as an intravenous bolus of 400 mg over 15 min followed by a continuous infusion of 480 mg over 2 h (low dose) or 800 mg over 30 min followed by a continuous infusion of 960 mg over 2 h (high dose), according to the last dose of DOAC and the size of the dose, for patients with rivaroxaban-associated or apixaban-associated life-threatening and uncontrolled bleeding 1.
Some key points to consider when using Andexanet alfa for reversal of apixaban include:
- The dose and timing of the last apixaban dose
- The severity of the bleeding
- The availability of Andexanet alfa and alternative reversal agents
- The potential for interference with heparin anticoagulation
- The need for supportive measures to control bleeding.
Overall, the use of Andexanet alfa for reversal of apixaban is a complex process that requires careful consideration of the patient's individual circumstances and the potential risks and benefits of treatment, as outlined in the 2020 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants 1 and the European guideline on management of major bleeding and coagulopathy following trauma: sixth edition 1.
From the FDA Drug Label
In Study 1, healthy subjects (median age: 57 years; range: 50 to 73 years) received apixaban 5 mg twice daily for three and a half days to achieve steady-state. At three hours after the last apixaban dose (~ Cmax), ANDEXXA or placebo was administered Eight subjects received placebo, and 24 received ANDEXXA, administered as a 400 mg IV bolus followed by a 4 mg per minute continuous infusion for 120 minutes (total 480 mg).
The results of Study 1 are provided below (see Table 4).
Table 4 - A: Change in Anti-FXa Activity/Study 1 (apixaban)
Mean % (± SD) change from baseline at the nadir* -92.3(2.8)
The reversal strategy for apixaban (Eliquis) is andexanet alfa (IV) administered as a 400 mg IV bolus followed by a 4 mg per minute continuous infusion for 120 minutes (total 480 mg) 2. This regimen has been shown to significantly reduce anti-FXa activity, with a mean percent change from baseline at nadir of -92.3%.
From the Research
Reversal Strategy for Apixaban (Eliquis)
The reversal strategy for apixaban (Eliquis) involves the use of specific agents to reverse its anticoagulant effects in cases of life-threatening or uncontrolled bleeding.
- Andexanet alfa is a modified human factor Xa approved for anticoagulation reversal in patients with life-threatening bleeding treated with rivaroxaban or apixaban 3.
- Four-factor prothrombin complex concentrates (4F-PCCs) are also used for reversal of apixaban, although their mechanism and effectiveness are not as well understood as andexanet alfa 4, 5, 6.
Comparison of Reversal Agents
Studies have compared the clinical outcomes of patients who received andexanet alfa or 4F-PCC for reversal of apixaban or rivaroxaban in the setting of intracranial hemorrhage.
- One study found that the rate of effective hemostasis was similar between the 4F-PCC and andexanet alfa groups (66.7% vs 75%, p = 0.62) 5.
- Another study found that hemostatic efficacy occurred in 64.7% of patients receiving andexanet alfa and 54.8% of receiving 4F-PCC, with 30-day all-cause mortality being lower in the andexanet alfa group (30% vs 45.2%) 6.
Safety and Efficacy
The safety and efficacy of andexanet alfa and 4F-PCC for reversal of apixaban have been evaluated in several studies.