Coagulation Factor Xa Recombinant, Inactivated-zhzo

Andexanet alfa is used for patients treated with rivaroxaban and apixaban when reversal of anticoagulation is needed because of life-threatening or uncontrolled bleeding.

Andexanet alfa is available under the following different brands and other names: coagulation factor Xa recombinant inactivated-zhzo and AndexXa.

Dosages of Andexanet Alfa:

Dosage Forms and Strengths

• 100mg/single-use vial

Dosage Considerations – Should be Given as Follows: 

Factor Xa Reversal

• Indicated for patients treated with rivaroxaban and apixaban, when reversal of anticoagulation is needed because of life-threatening or uncontrolled bleeding
• There are 2 dosage regimens (low dose or high dose) to choose from
• The safety and efficacy of an additional dose has not been established
• Safety and efficacy not established in pediatric patients

Low or high dose regimens 

• Low dose
  • Initial IV bolus: 400 mg intravenously (IV); target infusion rate of 30 mg/minute
  • Follow-on IV infusion: 4 mg/minute IV for up to 120 minutes

• High dose
  • Initial IV bolus: 800 mg IV; target infusion rate of 30 mg/minute
  • Follow-on IV infusion: 8 mg/minute IV for up to 120 minutes

Dose based on rivaroxaban or apixaban dose

• Use low dose described above
  • Rivaroxaban dose up to 10 mg (any timing from the last dose)
  • Apixaban dose up to 5 mg (any timing from the last dose)
  • Rivaroxaban greater than 10 mg or dose unknown (8 hours or more from the last dose)
  • Apixaban greater than 5 mg or dose unknown 8 hours or more from the last dose)

• Use high dose described above
  • Rivaroxaban greater than 10 mg or dose unknown (less than 8 hours from the last dose or unknown)
  • Apixaban greater than 5 mg or dose unknown (less than 8 hours from the last dose or unknown)

Dosing Considerations

Accelerated approval

• Approved under accelerated approval based on the change from baseline in anti-FXa activity in healthy volunteers
• An improvement in hemostasis has not been established
• Continued approval for this indication may be contingent upon the results of studies to demonstrate an improvement in hemostasis in patients

Limitation of use

• Has not been shown effective for, and is not indicated for, treatment of bleeding related to any FXa inhibitors other than apixaban and rivaroxaban

Restarting antithrombotic therapy

• Patients treated with FXa inhibitor therapy have underlying disease states that predispose them to thromboembolic events, thus reversing FXa inhibitor therapy exposes patients to the thrombotic risk of their underlying disease
• To reduce the risk of thrombosis, resume anticoagulant therapy as soon as medically appropriate after dose
   

Common side effects of andexanet alfa include:

• Infusion-related reactions
• Thromboembolic events
  • Deep vein thrombosis (DVT)
  • Ischemic stroke
  • Heart attack (acute myocardial infarction)
  • Pulmonary embolism (PE)
  • Cardiogenic shock
  • Sudden death
  • Congestive heart failure
  • Acute respiratory failure
  • Cardiac arrest
  • Cardiac thrombus
  • Embolic stroke
  • Iliac artery thrombosis
  • Nonsustained ventricular tachycardia
  • Deaths due to bleeding less than 30 days post-dose
  • Intracranial bleeding
  • Gastrointestinal bleeding
  • Other bleeding types

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Andexanet alfa has no listed severe interactions with other drugs.
• Andexanet alfa has no listed serious interactions with other drugs.
• Andexanet alfa has no listed moderate interactions with other drugs.
• Andexanet alfa has no listed mild interactions with other drugs.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings

• This medication contains andexanet alfa. Do not take <brand name drug name> if you are allergic to andexanet alfa or any ingredients contained in this drug.
• Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Black Box Warnings

• Serious and life-threatening adverse effects
• Monitor for thromboembolic events and initiate anticoagulation when medically appropriate
• Monitor for symptoms and signs that precede cardiac arrest and provide treatment as needed
• Treatment has been associated with the following serious and life-threatening adverse events, including
  • Arterial and venous thromboembolic events
  • Ischemic events, including myocardial infarction and ischemic stroke
  • Cardiac arrest
  • Sudden deaths

Contraindications

• None

Effects of Drug Abuse

• No information is available

Short-Term Effects

• See "What Are Side Effects Associated with Using Andexanet Alfa?”

Long-Term Effects

• See "What Are Side Effects Associated with Using Andexanet Alfa?”

Cautions

• Arterial and venous thromboembolic events, ischemic events, and cardiac events, including sudden death, were observed within 30 days after administration
• Reelevation or incomplete reversal of anti-FXa activity
• Compared with baseline, the ANNEXA-4 clinical trial observed a rapid and substantial decrease in anti-FXa activity corresponding to the IV bolus that was sustained through the end of the continuous infusion
• Following the infusion, there was an increase in anti-FXa activity, which peaked 4 hours after infusion
• After this peak, the antiFXa activity decreased at a rate similar to the clearance of the FXa inhibitors
• Approximately 50% of patients experience a greater than 90% decrease from baseline anti-FXa activity after administration

Pregnancy and Lactation

• Data are not available regarding use of andexanet alfa in pregnant women to inform patients of associated risks. The safety of andexanet alfa during labor and delivery has not been evaluated. Animal reproductive and development studies have not been conducted with andexanet alfa.
• Data are not available regarding the presence of andexanet alfa in human milk, the effects on breastfed children, or the effects on milk production. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for andexanet alfa and any potential adverse effects on the breastfed child or from the underlying maternal condition.