Reversal agent
Andexanet alfa (Andexxa)
Also called Andexxa
Watch the explainer
Heparin vs Warfarin: aPTT vs INR, HIT, Bridging, Antidotes and DOAC Reversal
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 |
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
- Bleeding, Reversal, HIT and DICReversing anticoagulants in major bleeding: Apixaban, rivaroxaban: 4F-PCC 50 units/kg (or 2,000 units fixed): Andexanet off US market Dec 2025; NCS/SCCM 2026 prefers PCC
- Blood Products and TransfusionAnticoagulant reversal: Apixaban, rivaroxaban: 4F-PCC, off-label (ACC 2020: 2,000 units): Andexanet withdrawn in the US, Dec 2025
- Neuro: ICP and StrokeHemorrhagic stroke (ICH): Dabigatran: idarucizumab. Factor Xa inhibitors: 4F-PCC (older answer: andexanet, off US market 2025)
- Subarachnoid HemorrhagePreventing rebleeding: BP, reversal, securing: Nicardipine, clevidipine and labetalol titrate fast (doses on the drip cards); nitroprusside and nitroglycerin dilate cerebral vessels and can raise ICP. Reverse anticoagulants at once (Class 1): 4F-PCC plus IV vitamin K for warfarin, idarucizumab for dabigatran, 4F-PCC for factor Xa inhibitors (NCS/SCCM 2026; andexanet left the US market in December
- Trauma: Primary and Secondary SurveyOlder adults and pregnancy: After 65, vital signs mislead: beta-blockers and pacemakers fix the heart rate, and chronic hypertension makes a normal-looking pressure relative hypotension. SBP below 90 identifies only 4–5% of seriously injured older adults, so the 2021 national field triage guideline uses SBP below 110 or heart rate above SBP. An EAST multicenter study (Ho 2025) supports head and ce
Practice Bleeding, Reversal, HIT and DIC questions free34 exam-style questions with rationales on the topic where Andexanet alfa comes up most. No account or download needed.
Other reversal agent drugs
Practice free in your browser3,800+ exam-style questions with rationales. No account, no ads. Also free on the App Store and Google Play.
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.