From the Guidelines
Andexanet alfa (Andexxa) is the recommended reversal agent for Eliquis (apixaban), administered as a bolus followed by a 2-hour infusion, with dosing based on the timing and amount of the last Eliquis dose, as supported by the most recent study 1. For patients with life-threatening bleeding or requiring emergency surgery while on Eliquis, the dosing of andexanet alfa depends on the timing since last intake:
- For patients who took Eliquis within the last 8 hours or with unknown timing, a high dose is recommended (800 mg bolus followed by 960 mg infusion) 1.
- For those who took Eliquis more than 8 hours prior, a low dose is used (400 mg bolus followed by 480 mg infusion) 1. If Andexanet alfa is unavailable, prothrombin complex concentrate (PCC) at 25-50 units/kg can be used as an alternative, as suggested by previous studies 1. Additional supportive measures include:
- Activated charcoal if Eliquis was ingested within 2-4 hours
- Discontinuation of Eliquis
- Local hemostatic measures Andexanet alfa works by acting as a decoy protein that binds to Eliquis, preventing it from inhibiting factor Xa and thus restoring normal coagulation, with reversal effects beginning within minutes but are temporary, lasting about 1-2 hours after completion of the infusion, as reported in 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) Study 1 ANNEXA-A (NCT02207725) – apixaban reversal Study 2 ANNEXA-R (NCT02220725) – rivaroxaban reversal In Study 1 and Study 2, the percent change from baseline in anti-FXa activity at its nadir was statistically significant (p < 0. 0001) in favor of the ANDEXXA groups compared to placebo in both Studies 1 and 2.
The FDA drug label does not answer the question about reversal for Eliquis.
From the Research
Reversal Agents for Eliquis (Apixaban)
- Andexanet alfa and four-factor prothrombin complex concentrate (4F-PCC) are two reversal agents used for apixaban-associated bleeding 2, 3, 4, 5.
- Andexanet alfa is a specific antidote for factor Xa inhibitors, including apixaban, and has been shown to be effective in achieving hemostatic efficacy in patients with intracranial hemorrhage (ICH) 3, 4.
- 4F-PCC is a non-specific reversal agent that has been used off-label for apixaban-associated bleeding, but its effectiveness and safety are still being investigated 2, 3, 4, 5.
Efficacy of Reversal Agents
- Studies have shown that andexanet alfa is associated with higher rates of hemostatic efficacy and lower mortality compared to 4F-PCC in patients with apixaban-associated ICH 3, 4.
- However, one study found that the rates of effective hemostasis were similar between 4F-PCC and andexanet alfa groups 5.
- The choice of reversal agent may depend on the specific clinical scenario and the availability of the agents.
Safety of Reversal Agents
- Thrombotic events have been reported with both andexanet alfa and 4F-PCC, but the risk appears to be higher with 4F-PCC 3, 4.
- Heparin resistance and pump thrombosis have been reported with sequential use of PCC and andexanet alfa for apixaban reversal during acute type A aortic dissection repair 6.
- Further studies are needed to fully understand the safety and efficacy of these reversal agents.