How to reverse International Normalized Ratio (INR) on Eliquis (apixaban)?

From the Guidelines

Reversal of Eliquis (apixaban) is achieved with Andexanet alfa, a recombinant modified human factor Xa protein that binds and sequesters the factor Xa inhibitors.

Key Points

• Andexanet alfa is specifically licensed for the reversal of apixaban or rivaroxaban in patients with major bleeding 1.
• The dosing of Andexanet alfa is based on the patient's last dose of apixaban or rivaroxaban, with a low-dose regimen of 400-mg bolus at a target rate of 30 mg/min followed by 4 mg/min for up to 120 min, and a high-dose regimen of 800-mg bolus at a target rate of 30 mg/min followed by 8 mg/min for up to 120 min 1.
• Andexanet alfa has a rapid onset of action, within 2 minutes, and a duration of action of 2 hours 1.
• Monitoring of coagulation parameters is not recommended after Andexanet alfa administration, as current commercial anti-Xa activity assays are unsuitable for measuring factor Xa activities after Andexanet alfa use 1.
• Andexanet alfa may interfere with the anticoagulation effect of heparin, and its use should be cautious in patients with thromboembolic events in the previous 3 months 1.

Clinical Considerations

• The decision to reverse apixaban should be based on the patient's individual risk of bleeding and thromboembolism, and should be made in consultation with a multidisciplinary team 1.
• In patients with atrial fibrillation, the use of Andexanet alfa for reversal of apixaban should be considered in the context of the patient's overall management plan, including the use of other anticoagulants and antiarrhythmic medications 1.

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

To reverse International Normalized Ratio (INR) on Eliquis (apixaban), an agent to reverse the anti-factor Xa activity of apixaban is available. Prothrombin complex concentrate (PCC), activated prothrombin complex concentrate, or recombinant factor VIIa may be considered, but their use has not been evaluated in clinical studies.

• 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 when PCCs are used.
• Protamine sulfate and vitamin K are not expected to affect the anticoagulant activity of apixaban. 2

From the Research

Reversal of Apixaban Anticoagulation

To reverse International Normalized Ratio (INR) on Eliquis (apixaban), the following options can be considered:

• Four-factor prothrombin complex concentrates (PCCs) may reverse the effect of apixaban, as shown in a study where both Cofact and Beriplex reversed apixaban's steady-state effects on several coagulation assessments 3.
• Andexanet alfa has been approved for apixaban reversal in patients with life-threatening bleeding, but its use is not indicated in cases without evidence of bleeding 4.
• Discontinuation of apixaban and administration of vitamin K may also be effective in managing elevated INR, as seen in a case report where vitamin K and changing antimicrobial therapy from cefazolin to daptomycin successfully managed laboratory abnormalities and bleeding concerns 5.

Monitoring INR Reversal

Point-of-care INR coagulometers (POC) can be used to guide reversal of oral anticoagulation at the bedside, hastening management of acute subdural hemorrhage 6.

• POC can provide rapid INR measurements, allowing for timely adjustment of prothrombin complex concentrate (PCC) dosing.
• The use of POC can reduce the time required for INR reversal and may also reduce the calculated PCC dose needed.

Important Considerations

• INR monitoring is not recommended for monitoring anticoagulant activity of direct oral anticoagulants (DOACs) like apixaban 4.
• Plasma concentration of DOACs has been found to correlate with INR, suggesting that high INR values may be secondary to high serum concentrations of apixaban 4.
• Further studies are necessary to address questions about the safety of DOACs in patients with end-stage renal disease and to establish appropriate management guidelines for elevated INR values associated with DOACs 4.