Andexanet Alfa
/api/v1/drug/andexanet-alfaBoxed warning
THROMBOEMBOLIC RISKS, ISCHEMIC RISKS, CARDIAC ARREST, AND SUDDEN DEATHS Treatment with ANDEXXA has been associated with serious and life-threatening adverse events, including: ( 5.1 ) • Arterial and venous thromboembolic events • Ischemic events, including myocardial infarction and ischemic stroke • Cardiac arrest • Sudden deaths Monitor for thromboembolic events and initiate anticoagulation when medically appropriate. Monitor for symptoms and signs that precede cardiac arrest and provide treatment as needed. WARNING: THROMBOEMBOLIC RISKS, ISCHEMIC RISKS, CARDIAC ARREST, and SUDDEN DEATHS See full prescribing information for complete boxed warning Treatment with ANDEXXA has been associated with serious and life-threatening adverse events, including: ( 5.1 ) • Arterial and venous thromboembolic events • Ischemic events, including myocardial infarction and ischemic stroke • Cardiac arrest • Sudden deaths Monitor for thromboembolic events and initiate anticoagulation when medically appropriate. Monitor for symptoms and signs that precede cardiac arrest and provide treatment as needed.
Mechanism of action
Sourced from openFDACoagulation factor Xa (recombinant), inactivated-zhzo exerts its procoagulant effect by binding and sequestering the FXa inhibitors, rivaroxaban and apixaban. Another observed procoagulant effect of the ANDEXXA protein is its ability to bind to, and inhibit the activity of, Tissue Factor Pathway Inhibitor (TFPI).
Indications
Sourced from openFDA- ANDEXXA is indicated for patients treated with rivaroxaban or apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding. This indication is approved under accelerated approval based on the change from baseline in anti-FXa activity in healthy volunteers [see Clinical Studies (14) ] .
Contraindications
Sourced from openFDA- None. None.contraindicated
Dosage & administration
Sourced from openFDAFor intravenous (IV) use only. • Dose ANDEXXA based on the specific FXa inhibitor, dose of FXa inhibitor, and time since the patient's last dose of FXa inhibitor. ( 2 ) • Administer as an IV bolus, with a target rate of 30 mg/min, followed by continuous infusion for 120 minutes. ( 2.3 ) • There are two dosing regimens: Dose The safety and effectiveness of more than one dose have not been evaluated. ( 2.1 ) Initial IV Bolus Follow-On IV Infusion Low Dose 400 mg at a target rate of 30 mg/min 4 mg/min for 120 minutes High Dose 800 mg at a target rate of 30 mg/min 8 mg/min for 120 minutes 2.1 Dose For intravenous (IV) use only. There are two dosing regimens (see Table 1 ). The safety and efficacy of an additional dose have not been established. Table 1: ANDEXXA Dosing Regimens Dose The safety and effectiveness of more than one dose have not been evaluated. Initial IV Bolus Follow-On IV Infusion Total Number of 200 mg Vials Low Dose 400 mg at a target rate of 30 mg/min 4 mg/min for 120 minutes (480 mg) 5 (2 vials bolus + 3 vials infusion) High Dose 800 mg at a target rate of 30 mg/min 8 mg/min for 120 minutes (960 mg) 9 (4 vials bolus + 5 vials infusion) The recommended dosing of ANDEXXA is based on the specific FXa inhibitor, dose of FXa inhibitor, and time since the patient's last dose of FXa inhibitor (see Table 2 ).
Warnings & precautions
Sourced from openFDA• Arterial and venous thromboembolic events, ischemic events, and cardiac events, including sudden death, have occurred during treatment with ANDEXXA. Resume anticoagulant therapy as soon as medically appropriate following treatment with ANDEXXA . ( 5.1 ) • Unresponsiveness to unfractionated heparin has been reported following ANDEXXA administration. ( 5.2 ) • Re-elevation or incomplete reversal of anticoagulant activity can occur. ( 5.3 ) 5.1 Thromboembolic and Ischemic Risks The thromboembolic and ischemic risks were assessed in 419 bleeding -patients in the ANNEXA-4 study who received ANDEXXA and were treated with apixaban or rivaroxaban. There were 45/419 (10.7%) patients who experienced a thrombotic event. The median time to first event was 10 days, and 17 patients experienced the event within three days of treatment. Of the 419 patients who received ANDEXXA, 266 received at least one anticoagulation dose within 30 days after treatment as a prophylactic measure. Of these 266 patients, 14 patients (5.3%) had a thrombotic event after resumption [ see Adverse Reactions (6.1) ]. Monitor patients treated with ANDEXXA for signs and symptoms of arterial and venous thromboembolic events, ischemic events, and cardiac arrest. To reduce thromboembolic risk, resume anticoagulant therapy as soon as medically appropriate following treatment with ANDEXXA [ see Dosage and Administration (2.4) ].
Adverse reactions
Sourced from openFDAThe most common adverse reactions (≥ 5%) in bleeding patients receiving ANDEXXA were urinary tract infections and pneumonia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The most common adverse reactions (≥ 5%) in bleeding patients receiving ANDEXXA were urinary tract infections and pneumonia. In Study 3 (ANNEXA-4), four hundred and seventy-seven patients with acute major bleeding were enrolled and received ANDEXXA. Of these 477 patients, 419 patients were treated with apixaban (245/419; 58.5%) or rivaroxaban (174/419; 41.5%). Most patients had received apixaban or rivaroxaban as anticoagulation treatment for atrial fibrillation (348/419; 83%) or venous thromboembolism (65/419; 16%). In the majority of patients, ANDEXXA was used to reverse anticoagulant therapy following either an intracranial hemorrhage (289/419; 69%) or a gastrointestinal bleed (95/419; 23%), with the remaining patients (35/419; 8.4%) experiencing bleeding at other sites. Patients were assessed at a Day 30 follow-up visit following infusion with ANDEXXA. Deaths In the ANNEXA-4 study, of the 419 patients in the safety population who were treated with apixaban or rivaroxaban, there were 75 deaths (18%).
Use in specific populations
Sourced from openFDA8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of ANDEXXA in pregnant women to inform patients of associated risks. Animal reproductive and developmental studies have not been conducted with ANDEXXA. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Labor or Delivery The safety and effectiveness of ANDEXXA during labor and delivery have not been evaluated. 8.2 Lactation Risk Summary There is no information regarding the presence of ANDEXXA in human milk, the effects on the breastfed child, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ANDEXXA and any potential adverse effects on the breastfed child from ANDEXXA or from the underlying maternal condition. 8.4 Pediatric Use The safety and efficacy of ANDEXXA in the pediatric population have not been studied. 8.5 Geriatric Use Of the 419 patients in the ANNEXA-4 study of ANDEXXA, 381 (91%) were 65 years of age or older, and 278 (66%) were older than 75 years of age.
Pharmacokinetics
Sourced from openFDA- Metabolism
- A summary of the pharmacokinetic (PK) properties of ANDEXXA in healthy patients is shown in the table below (see Table 3 ). Table 3: Summary of PK Parameters with High and Low Doses Low Dose High Dose Data presented are geometric mean (Geometric Mean % Coefficient of Variation), [range].
FAERS reports
- 1Death12418%
- 2Cerebral Infarction547.7%
- 3Off Label Use527.4%
- 4Acute Myocardial Infarction365.1%
- 5Ischaemic Stroke365.1%
- 6Cerebral Haemorrhage334.7%
- 7Heparin Resistance334.7%
- 8Pulmonary Embolism334.7%
- 9Cerebrovascular Accident304.3%
- 10Myocardial Infarction304.3%
- 11Thrombosis273.9%
- 12Haemorrhage243.4%
- 13Subdural Haematoma192.7%
- 14Deep Vein Thrombosis182.6%
- 15Drug Interaction162.3%
Clinical trials
The 10 most recently updated of 18 ClinicalTrials.gov registrations naming Andexanet Alfa as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.
- A Study to Investigate Andexanet Dosing and the Interaction Between Andexanet and Subsequent Enoxaparin in Healthy ParticipantsActive not recruiting · Phase 1 · Interventional · 179 enrolled · AstraZenecaNCT07312851updated 2026-06-02
- Andexanet Alfa: Non-interventional Study in Stroke Units in Germany (DE)Completed · Observational · 141 enrolled · University Hospital, EssenNCT05127941updated 2026-05-06
- Retrospective Study on Characteristics and Outcomes in Hospitalised Patients Treated With OndexxyaCompleted · Observational · 217 enrolled · AstraZenecaNCT05898412updated 2026-04-17
- A Study of Andexanet Alfa in Patients Requiring Urgent Surgery or ProcedureWithdrawn · Phase 3 · Interventional · 0 enrolled · AstraZenecaNCT05926349updated 2024-10-26
- Trial of Andexanet Alfa in ICrH Patients Receiving an Oral FXa InhibitorCompleted · Phase 4 · Interventional · 530 enrolled · Alexion Pharmaceuticals, Inc.NCT03661528updated 2024-07-03
- Andexanet Alfa and 4F-PCC Use in Patients Hospitalised With an Anticoagulant-related Major BleedCompleted · Observational · 5,480 enrolled · AstraZenecaNCT05548777updated 2023-11-28
- A Healthy Volunteer PK/PD, Safety and Tolerability Study of Andexanet After Betrixaban DosingTerminated · Phase 2 · Interventional · 18 enrolled · Portola PharmaceuticalsNCT03330457updated 2023-08-08
- A Healthy Volunteer PK/PD, Safety and Tolerability Study of Second Generation Andexanet AlfaCompleted · Phase 1 · Interventional · 153 enrolled · Portola PharmaceuticalsNCT03083704updated 2023-08-08
- A Study in Older Subjects to Evaluate the Safety and Ability of Andexanet Alfa to Reverse the Anticoagulation Effect of ApixabanCompleted · Phase 3 · Interventional · 68 enrolled · Portola PharmaceuticalsNCT02207725updated 2023-08-08
- Phase 2 Healthy Volunteer Study to Evaluate the Ability of PRT064445 to Reverse the Effects of Several Blood Thinner Drugs on Laboratory Tests (Module 1 of 4)Completed · Phase 2 · Interventional · 54 enrolled · Portola PharmaceuticalsNCT01758432updated 2023-08-07
Frequently asked questions
- How does Andexanet Alfa work?
- Coagulation factor Xa (recombinant), inactivated-zhzo exerts its procoagulant effect by binding and sequestering the FXa inhibitors, rivaroxaban and apixaban. Another observed procoagulant effect of the ANDEXXA protein is its ability to bind to, and inhibit the activity of, Tissue Factor Pathway Inhibitor (TFPI).
- What is Andexanet Alfa used for?
- According to FDA labeling, Andexanet Alfa carries indications including: ANDEXXA is indicated for patients treated with rivaroxaban or apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding. This indication is approved under accelerated approval based on the change from baseline in anti-FXa activity in healthy volunteers [see Clinical Studies (14) ] .. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
- What class of drug is Andexanet Alfa?
- Andexanet Alfa is classified as Antidotes, Enzyme Activators, Increased Coagulation Activity, Reversed Anticoagulation Activity.
- What are the brand names for Andexanet Alfa?
- Andexanet Alfa is marketed under brand names including Andexxa.
- What are the contraindications for Andexanet Alfa?
- Andexanet Alfa labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.
andexanet-alfa is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.