What is the reversal strategy for Apixaban (Eliquis)?

From the Guidelines

Eliquis (apixaban) can be reversed in emergency situations using Andexxa (andexanet alfa), which is specifically designed to reverse the anticoagulant effects of factor Xa inhibitors like Eliquis. The dosing of andexanet alfa depends on the timing since last intake of Eliquis: for patients who took Eliquis more than 8 hours prior, a low-dose regimen of Andexxa is typically used: 400mg IV bolus followed by a 480mg continuous infusion over 2 hours 1. For patients who took Eliquis less than 8 hours prior, a high-dose regimen of Andexxa is typically used: 800mg IV bolus followed by a 960mg continuous infusion over 2 hours 1. Andexxa works by binding to the anticoagulant and preventing it from inhibiting factor Xa, thus restoring normal blood clotting 2. In settings where Andexxa is unavailable, prothrombin complex concentrate (PCC) at 25-50 units/kg can be used as an alternative, though it's less specific and less effective 3. For non-life-threatening bleeding, supportive measures and temporarily discontinuing Eliquis may be sufficient. Reversal should only be performed in serious bleeding situations or emergency surgery, as reversing anticoagulation increases the risk of thrombotic events in patients who needed anticoagulation in the first place 4. Some key points to consider when using andexanet alfa include:

• The dose and timing of andexanet alfa administration depend on the specific factor Xa inhibitor being reversed and the timing of the last dose 5
• Andexanet alfa has been shown to be effective in reversing the anticoagulant effects of apixaban and rivaroxaban in clinical trials 1
• The use of andexanet alfa may be associated with a risk of thrombotic events, and its use should be carefully considered in patients with a history of thrombosis 2

From the FDA Drug Label

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. An agent to reverse the anti-factor Xa activity of apixaban is available

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

The results of Study 1 and Study 2 are provided below (see Table 4).

Mean % (± SD) change from baseline at the nadir* -92.3(2.8) -32.7(5.6)

Eliquis reversal can be achieved with andexanet alfa (ANDEXXA), which has been shown to significantly reduce anti-FXa activity in healthy subjects who received apixaban.

• The mean percent change from baseline in anti-FXa activity at its nadir was -92.3% in the ANDEXXA group compared to -32.7% in the placebo group.
• ANDEXXA is an agent that can reverse the anti-factor Xa activity of apixaban.
• The pharmacodynamic effect of apixaban can be expected to persist for at least 24 hours after the last dose. 6

From the Research

Eliquis Reversal Agents

Eliquis, also known as apixaban, is a factor Xa inhibitor used for anticoagulation. In cases of major bleeding, reversal agents may be necessary to counteract its effects.

• Andexanet alfa is a specific reversal agent for factor Xa inhibitors, including apixaban 7, 8, 9, 10.
• Four-factor prothrombin complex concentrates (4F-PCC) are also used as a non-specific reversal agent for factor Xa inhibitors, although their effectiveness may vary 7, 8, 11, 9.
• Studies have shown that andexanet alfa is associated with greater odds of achieving hemostatic effectiveness and decreased odds of mortality compared to 4F-PCC in patients with apixaban- or rivaroxaban-associated intracranial hemorrhage 7, 8.

Comparison of Reversal Agents

Comparative studies have evaluated the effectiveness of andexanet alfa and 4F-PCC in reversing apixaban and rivaroxaban.

• Andexanet alfa was found to be more effective in achieving hemostatic effectiveness and improving survival compared to 4F-PCC 7, 8.
• However, 4F-PCC may still be beneficial in managing major bleeding associated with oral Xa inhibitors, although the risk of thromboembolism should be considered 11.
• In vitro studies have also demonstrated that andexanet alfa is more effective in normalizing thrombin generation compared to 4F-PCC in the presence of apixaban or rivaroxaban 9.

Clinical Considerations

When considering reversal agents for Eliquis, clinicians should take into account the specific situation and the availability of reversal agents.

• Specific reversal agents, such as andexanet alfa, are preferred when available due to their efficacy and safety 10.
• Nonspecific prohemostatic agents, such as 4F-PCC, may be used in emergency situations when specific reversal agents are unavailable 10.
• Clinicians should also be aware of the potential risks and complications associated with reversal agents, including thromboembolism 11, 10.