Reversal agent

Andexanet alfa (Andexxa)

Also called Andexxa

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Indications

Life-threatening or uncontrolled bleeding on apixaban or rivaroxaban (US accelerated approval 2018; US sales ended December 22, 2025)
Factor Xa inhibitor-associated intracranial hemorrhage, its main use in trials (ANNEXA-4, ANNEXA-I)
Still sold outside the US as Ondexxya (EU conditional approval, UK, Japan)
Edoxaban or enoxaparin bleeding (off-label; not shown effective)

Dosing

Where	Dose
Reversal and antidotes	Andexanet alfa: Off the US market since December 2025 (thrombosis in ANNEXA-I); for apixaban or rivaroxaban bleeding give 4F-PCC 50 units/kg

On the quick cards

Direct oral anticoagulants (-xaban, dabigatran)NCLEX Drug Classes: AF stroke prevention, DVT and PE

Mechanism of action

Andexanet alfa is a decoy: recombinant human factor Xa whose catalytic serine is replaced by alanine and whose Gla domain is removed. Its intact active-site pocket binds apixaban and rivaroxaban 1:1 with high affinity, sequestering them so the patient's own factor Xa can make thrombin again; 1:1 binding is why the doses are so large. Without the Gla domain it cannot join the prothrombinase complex, and it has no enzyme activity. It also binds and inhibits tissue factor pathway inhibitor (TFPI) and binds heparin–antithrombin complexes, raising thrombin generation and causing heparin resistance.

Pharmacology

Hematologic: anti-factor Xa activity falls 92–97% within 2 min of the bolus (label)
Hematologic: rebound: anti-Xa activity returns to placebo levels about 2 h after the infusion ends (label), as andexanet falls while the longer-lived inhibitor remains
Hematologic: TFPI inhibition keeps tissue factor-driven thrombin generation above placebo for at least 22 h; TFPI recovers by about 96 h (label)
Cardiovascular: thrombotic events (stroke, DVT, MI, PE) in 10.7% of ANNEXA-4 patients, at a median of 10 days (label)

Pharmacokinetics

Onset	Within 2 min of the bolus
Duration	Only as long as the infusion runs, plus about 2 h (label)
Half-life	About 3 h (2.7–3.3 h; label)
Distribution	Vss 3.0–4.4 L, about plasma volume (label)
Metabolism	Presumably proteolysis like other proteins; not characterized in the label
Clearance	3.1–4.4 L/h (label)
Routes	IV bolus at 30 mg/min, then a 2-h infusion
Monitoring	Commercial anti-Xa assays read falsely high after andexanet, so judge reversal clinically (label)

Chemistry

Recombinant modified human factor Xa (coagulation factor Xa, recombinant, inactivated-zhzo) made in CHO cells: a glycoprotein of about 41 kDa (label)
Two chains joined by one disulfide bond: a 105-amino acid light chain without the Gla domain and a 254-amino acid heavy chain with alanine at the catalytic serine
Lyophilized 200 mg vial; 20 mL sterile water gives 10 mg/mL; tris buffer, L-arginine, sucrose, mannitol and polysorbate 80; pH 7.8 (label)

Adverse effects and cautions

In the one-pagers

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Sources

FDA label: Andexxa (2025)
FDA safety communication: Andexxa (2025)
Connolly 2024 (ANNEXA-I, NEJM)

For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow the order, the label and your institution's protocols.