How to reverse apixaban (Eliquis)?

From the Guidelines

Reversing Eliquis (apixaban) is best achieved with Andexxa (andexanet alfa), a specific reversal agent that binds to the drug and reduces its anticoagulant effects, as demonstrated in the most recent study 1. To reverse Eliquis, the following steps can be taken:

• Administer Andexxa (andexanet alfa) as an intravenous bolus, followed by a 2-h infusion, according to the type of FXa inhibitor and timing of the last FXa inhibitor dose, as outlined in the ANNEXA-4 study 1.
• For apixaban, a 400 mg bolus is administered followed by a 480 mg infusion (4 mg/min), as specified in the study 1.
• In emergency situations where Andexxa is unavailable, prothrombin complex concentrate (PCC) at doses of 25-50 units/kg may be administered as an alternative, although this is not the preferred method.
• For non-life-threatening bleeding, discontinuation of Eliquis and supportive measures like local pressure, surgical hemostasis, fluid replacement, and blood product transfusion may be sufficient.
• Since Eliquis has a relatively short half-life of 12 hours, its effects will naturally diminish over time once the medication is stopped.
• Activated charcoal may be useful if the drug was recently ingested (within 2-6 hours), but hemodialysis is not effective for removing Eliquis from the bloodstream due to its high protein binding. The use of Andexxa (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, which is the most recent and highest quality study on this topic.

From the FDA Drug Label

An agent to reverse the anti-factor Xa activity of apixaban is available The pharmacodynamic effect of apixaban tablets can be expected to persist for at least 24 hours after the last dose, i.e., for about two drug half-lives. Prothrombin complex concentrate (PCC), activated prothrombin complex concentrate or recombinant factor VIIa may be considered, but have not been evaluated in clinical studies When PCCs are used, monitoring for the anticoagulation effect of apixaban using a clotting test (PT, INR, or aPTT) or anti-factor Xa (FXa) activity is not useful and is not recommended. Activated oral charcoal reduces absorption of apixaban, thereby lowering apixaban plasma concentration Hemodialysis does not appear to have a substantial impact on apixaban exposure Protamine sulfate and vitamin K are not expected to affect the anticoagulant activity of apixaban. There is no experience with antifibrinolytic agents (tranexamic acid, aminocaproic acid) in individuals receiving apixaban There is no experience with systemic hemostatics (desmopressin and aprotinin) in individuals receiving apixaban and they are not expected to be effective as a reversal agent.

To reverse Eliquis (apixaban), an agent to reverse the anti-factor Xa activity is available.

• Andexanet alfa is specifically approved for this purpose, as seen in the studies 2.
• Alternatively, prothrombin complex concentrate (PCC), activated prothrombin complex concentrate, or recombinant factor VIIa may be considered, but their effectiveness has not been evaluated in clinical studies.
• Activated oral charcoal can reduce absorption of apixaban. It is essential to note that the effectiveness of these reversal methods may vary, and the choice of method should be made on a case-by-case basis, considering the individual patient's situation and the severity of the bleeding. Always consult the latest clinical guidelines and seek expert advice when managing anticoagulant reversal.

From the Research

Reversal of Eliquis (Apixaban)

Eliquis, also known as apixaban, is a direct oral anticoagulant (DOAC) that works by inhibiting factor Xa. Reversing its effects can be crucial in emergency situations, such as major bleeding or the need for urgent surgery.

• The available evidence suggests that there are specific reversal agents for DOACs, including andexanet alfa for factor Xa inhibitors like apixaban 3.
• Andexanet alfa has been shown to be effective in reversing the anticoagulant effects of apixaban and rivaroxaban in patients with intracranial hemorrhage 4.
• Prothrombin complex concentrate (PCC) may also be used as a nonspecific reversal agent for apixaban, although its effectiveness may vary 5.
• Guidelines recommend the use of specific reversal agents, such as andexanet alfa, for DOAC reversal in severe bleeding situations, but also suggest that PCC may be used off-label when specific reversal agents are unavailable 6.

Considerations for Reversal

When considering reversal of apixaban, it is essential to weigh the benefits and risks of supporting hemostasis versus post-reversal thrombosis.

• The decision to reverse anticoagulation should be made on a case-by-case basis, taking into account the severity of bleeding, the need for urgent surgery, and the patient's individual risk factors 7.
• Clinicians should be aware of the available reversal agents, their mechanisms of action, and their potential side effects, as well as the importance of monitoring for post-reversal complications 3.