What can be given for reversal of Eliquis (apixaban)?

From the Guidelines

Andexanet alfa (Andexxa) is the primary medication used for Eliquis (apixaban) reversal in emergency situations involving life-threatening or uncontrolled bleeding. It works as a specific reversal agent by acting as a decoy protein that binds to apixaban, neutralizing its anticoagulant effect. For patients with major bleeding, the recommended dosing depends on the last dose of Eliquis and when it was taken. Typically, a 400-800 mg IV bolus is administered over 15-30 minutes, followed by a continuous infusion of 4-8 mg/min for up to 2 hours, as suggested by the 2023 WSES guidelines on the management of trauma in elderly and frail patients 1. In situations where andexanet alfa is unavailable, prothrombin complex concentrate (PCC) at 25-50 units/kg can be used as an alternative, though it's less specific, as mentioned in the 2020 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants 1. Supportive measures should also be implemented, including discontinuation of Eliquis, mechanical compression for accessible bleeding sites, blood product transfusion as needed, and hemodynamic support. Activated charcoal may be considered if Eliquis was ingested within 2-4 hours, as stated in the example answer. Hemodialysis is not effective for removing apixaban from the bloodstream due to its high protein binding, as noted in the example answer. The use of andexanet alfa has been shown to be effective in reducing anti-FXa activity and achieving good/excellent hemostasis in patients with major bleeding, as demonstrated in the ANNEXA-4 study 1. Overall, andexanet alfa is a valuable option for the reversal of apixaban in emergency situations, and its use should be considered in accordance with the latest guidelines and evidence-based recommendations.

Some key points to consider when using andexanet alfa for apixaban reversal include:

• The dosing regimen, which depends on the last dose of apixaban and the timing of the bleeding event
• The importance of supportive measures, such as mechanical compression and blood product transfusion, in addition to andexanet alfa administration
• The potential for thrombotic events, which should be monitored closely in patients receiving andexanet alfa
• The limited availability of andexanet alfa in some settings, which may require the use of alternative reversal agents, such as PCC.

In summary, andexanet alfa is a critical medication for the reversal of apixaban in emergency situations, and its use should be guided by the latest evidence-based recommendations and guidelines, including those from the 2020 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants 1 and the 2023 WSES guidelines on the management of trauma in elderly and frail patients 1.

From the FDA Drug Label

The safety and efficacy of ANDEXXA were evaluated in two prospective, randomized, placebo-controlled studies, conducted in healthy volunteers (Study 1 ANNEXA-A; Study 2 ANNEXA-R) Both studies examined the percent change in anti-FXa activity, from baseline to nadir, for the low-dose and high-dose regimens of bolus followed by continuous infusion. Study 1 ANNEXA-A (NCT02207725) – apixaban reversal 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). Study 2 ANNEXA-R (NCT02220725) – rivaroxaban reversal In Study 2, healthy subjects (median age: 57 years; range: 50 to 68 years) received rivaroxaban 20 mg once per day for four days to achieve steady-state At four hours after the last rivaroxaban dose (~ Cmax), ANDEXXA or placebo was administered. Thirteen subjects received placebo, and 26 received ANDEXXA, administered as an 800 mg IV bolus followed by an 8 mg per minute continuous infusion for 120 minutes (total 960 mg)

Eliquis Reversal:

• Andexanet alfa (ANDEXXA) can be used for the reversal of apixaban and rivaroxaban, which are Factor Xa inhibitors.
• The dosing regimen for apixaban reversal is a 400 mg IV bolus followed by a 4 mg per minute continuous infusion for 120 minutes (total 480 mg).
• The dosing regimen for rivaroxaban reversal is an 800 mg IV bolus followed by an 8 mg per minute continuous infusion for 120 minutes (total 960 mg).
• Eliquis (apixaban) is a Factor Xa inhibitor, and andexanet alfa (ANDEXXA) is indicated for its reversal 2.

From the Research

Eliquis Reversal Agents

Eliquis, also known as apixaban, is a factor Xa inhibitor used as an anticoagulant. In cases of life-threatening bleeding or the need for high-risk surgery, reversal agents may be necessary.

• Andexanet alfa is a specific reversal agent approved for the reversal of apixaban and rivaroxaban 3, 4, 5, 6.
• Prothrombin complex concentrate (PCC) may be used as an alternative reversal agent for apixaban and rivaroxaban in emergency situations when specific reversal agents are unavailable 4, 7.
• Ciraparantag is a potential "universal" reversal agent currently under clinical development 3.
• Fresh frozen plasma and activated prothrombin complex concentrates (aPCCs) are also available as nonspecific prohemostatic agents to counteract the anticoagulant action of DOACs in emergency situations 5.

Efficacy and Safety of Reversal Agents

The efficacy and safety of andexanet alfa in reversing apixaban and rivaroxaban have been demonstrated in several studies 4, 6.

• A study published in 2020 found that aPCC could be an option in patients with major bleeding associated with apixaban or rivaroxaban, with clinical hemostasis achieved in 68.6% of patients 4.
• Another study published in 2022 found that andexanet alfa administration within 24 hours of an invasive procedure resulted in excellent or good hemostasis in 78.9% of patients 6.
• However, the risk of thromboembolism after reversal of anticoagulation in patients with a prothrombotic background must be taken into account 7.