From the Guidelines
To reverse the effects of Eliquis (apixaban), the primary option is the medication Andexxa (coagulation factor Xa, recombinant, inactivated-zhzo), which is specifically designed to reverse factor Xa inhibitors like Eliquis. The dosing of Andexxa depends on the dose of Eliquis and when it was last taken, as outlined in the 2020 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants 1. For patients on higher doses or who took Eliquis recently, a high dose of Andexxa is given as an IV bolus over 15-30 minutes, followed by a 2-hour infusion. The specific dosing recommendations are as follows:
- Administer low dose andexanet (400 mg IV bolus followed by 4 mg/min infusion for up to 120 minutes [480 mg]) if the last dose of rivaroxaban or apixaban was taken ≥8 hours prior, or if the last dose of rivaroxaban ≤10 mg was taken <8 hours prior, or if the last dose of apixaban ≤5 mg was taken <8 hours prior 1.
- Administer high dose andexanet (800 mg IV bolus followed by 8 mg/min infusion for up to 120 minutes [960 mg]) if the last dose of rivaroxaban >10 mg was taken <8 hours prior, or if the last dose of apixaban >5 mg was taken <8 hours prior, or if the timing of the last dose is unknown 1. In emergency situations where Andexxa isn't available, prothrombin complex concentrate (PCC) at 25-50 units/kg may be used as an alternative, though it's less effective, as noted in the 2023 WSES guidelines on the management of trauma in elderly and frail patients 1. Other supportive measures include discontinuing Eliquis immediately, delaying any planned procedures if possible, administering activated charcoal if the medication was taken within 2-4 hours, and providing blood products as needed. Reversal is typically only performed in life-threatening bleeding situations or before emergency surgery, as reversing anticoagulation increases the risk of blood clots that the Eliquis was originally prescribed to prevent, as highlighted in the ANNEXA-4 study 1. The efficacy and safety of Andexanet alfa for the reversal of apixaban and rivaroxaban have been demonstrated in clinical trials, including the ANNEXA-4 study, which showed that Andexanet alfa can effectively reverse the anticoagulant activity of these medications and achieve good or excellent hemostasis in the majority of patients 1. Overall, the use of Andexxa for the reversal of Eliquis is supported by the most recent and highest-quality evidence, including the 2020 ACC Expert Consensus Decision Pathway and the ANNEXA-4 study 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. In Study 1, healthy subjects 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). In Study 2, healthy subjects 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)
To reverse Eliquis (apixaban), administer ANDEXXA (andexanet alfa) as a 400 mg IV bolus followed by a 4 mg per minute continuous infusion for 120 minutes (total 480 mg) 2. To reverse rivaroxaban, administer ANDEXXA (andexanet alfa) as an 800 mg IV bolus followed by an 8 mg per minute continuous infusion for 120 minutes (total 960 mg) 2. Key points:
- Dose: 400 mg IV bolus + 4 mg/min infusion for apixaban, 800 mg IV bolus + 8 mg/min infusion for rivaroxaban
- Duration: 120 minutes
- Total dose: 480 mg for apixaban, 960 mg for rivaroxaban
From the Research
Reversal of Eliquis (Apixaban)
To reverse the effects of Eliquis (apixaban), several strategies can be employed:
- Administration of andexanet alfa, a specific reversal agent for Factor Xa inhibitors, which has been shown to completely reverse the anticoagulant activity of apixaban within minutes after administration without adverse effects 3.
- Use of activated charcoal, which can reduce apixaban exposure and facilitate its elimination when administered up to 6 hours after apixaban ingestion 4.
- Prothrombin complex concentrate (PCC) may also be used off-label for reversing Factor Xa inhibitors, including apixaban, in certain settings 5, 6.
- Ciraparantag, a universal reversal agent, is still in development and may offer an additional option for reversing apixaban in the future 5, 6.
Clinical Considerations
When managing patients on Eliquis who require reversal, it is essential to consider the following:
- The severity and location of bleeding, as well as the need for urgent surgery or invasive procedures 7.
- The timing of the last apixaban dose and the potential for ongoing anticoagulant effects 4.
- The availability and potential benefits and risks of different reversal strategies, including specific antidotes, activated charcoal, and PCC 5, 6, 3.