AndexXa

For intravenous use only.

Dose

There are two dosing regimens (see Table 1). The safety and efficacy of an additional dose has not been established.

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).

Reconstitution

Upon reconstitution, the parenteral drug product should be inspected visually for particulate matter and discoloration prior to administration.

• The reconstituted solution contains coagulation factor Xa (recombinant), inactivated-zhzo at a concentration of 10 mg/mL.
• Reconstituted Andexxa in vials is stable at room temperature for up to 8 hours, or may be stored for up to 24 hours at 2°C to 8°C.
• Reconstituted Andexxa in IV bags is stable at room temperature for up to 8 hours, or may be stored for up to 16 hours at 2°C to 8°C.

IV Bolus Preparation

• Reconstitute each 100 mg vial of Andexxa (Figure A) using a 10-mL syringe and 20-gauge (or higher) needle. Slowly inject 10 mL Sterile Water for Injection (SWFI), USP, directing the solution onto the inside wall of the vial to minimize foaming (Figure A).

  (Figure A)

• To reduce the total reconstitution time needed during preparation, reconstitute all required vials in succession.
• To ensure dissolution of the cake or powder, gently swirl each vial until complete dissolution of powder occurs. Do not shake; shaking could lead to foaming (Figure B). Typical dissolution time for each vial is approximately 3 to 5 minutes. If dissolution is incomplete, discard the vial and do not use the product.

  (Figure B)

• Use 60-mL or larger syringe with a 20-gauge (or higher) needle to withdraw the reconstituted Andexxa solution from each of the vials until the required dosing volume is achieved. Note the total volume withdrawn into the syringe.
• Transfer the Andexxa solution from the syringe into an empty polyolefin or polyvinyl chloride IV bag with a volume of 250 mL or less (Figure C).

  (Figure C)

• Discard the syringe and needle.
• Discard the vials, including any unused portion.

Continuous IV Infusion Preparation

• Follow the same procedure outlined above for IV bolus preparation. Reconstitute the number of vials needed based on the dose requirements. More than one 40 to 60-mL syringe, or an equivalent 100-mL syringe, may be used for transfer of reconstituted solution to the IV bag.
• Infusion will require a 0.2 or 0.22 micron in-line polyethersulfone or equivalent low protein-binding filter.

Administration

• Administer Andexxa intravenously, using a 0.2 or 0.22 micron in-line polyethersulfone or equivalent low protein-binding filter.
• Start the bolus at a target rate of approximately 30 mg/minute.
• Within 2 minutes following the bolus dose, administer the continuous IV infusion for up to 120 minutes.

Restarting Antithrombotic Therapy

Patients treated with FXa inhibitor therapy have underlying disease states that predispose them to thromboembolic events. 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 following treatment with Andexxa.

Andexxa (coagulation factor Xa (recombinant), inactivated-zhzo) is a sterile, white to off-white lyophilized powder available in single-use vials, containing 100 mg of coagulation factor Xa formulated with the inactive ingredients tromethamine (Tris), L-arginine hydrochloride, sucrose (2% w/v), mannitol (5% w/v), and polysorbate 80 (0.01% w/v) at pH 7.8. After reconstitution of the lyophilized powder with sterile Water for Injection for intravenous (IV) administration, the product is a clear, colorless to slightly yellow solution. Andexxa contains no preservatives.

The active ingredient in Andexxa is a genetically modified variant of human Factor Xa. The active site serine was substituted with alanine, rendering the molecule unable to cleave and activate prothrombin. The gamma-carboxyglutamic acid (Gla) domain was removed to eliminate the protein's ability to assemble into the prothrombinase complex, thus removing the potential anti-coagulant effects.

No additives of human or animal origin are used in the manufacture of Andexxa. The recombinant protein is produced in a genetically engineered Chinese Hamster Ovary (CHO) cell expression system and has a molecular weight of approximately 41 kDa. The manufacturing process incorporates two validated virus clearance steps.

Andexxa is part of the drug class:

• Blood coagulation factors

Use Andexxa (andexanet alfa) as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given into a vein for a period of time.

What do I do if I miss a dose?

• This medicine is given on an as needed basis.

Andexxa is a protein that reverses the effects of certain anticoagulant medications that are used to treat or prevent blood clots. Reversing anticoagulant medicine is necessary if you have uncontrolled or life-threatening bleeding as a result of how that medicine works.

Andexxa is used to treat uncontrolled bleeding in people who take the anticoagulants rivaroxaban (Xarelto) and apixaban (Eliquis).

Andexxa was approved by the US Food and Drug Administration (FDA) on an "accelerated" basis. In clinical studies, healthy volunteers responded to Andexxa, but further studies are needed.

Andexxa may also be used for purposes not listed in this medication guide.

You should not be treated with Andexxa if you have had an allergic reaction to clotting factor medicine.

In an emergency, you may not be able to tell caregivers about your health conditions. Make sure any doctor caring for you afterward knows you received Andexxa.

In an emergency, you may not be able to tell caregivers if you are pregnant or breast feeding. Make sure any doctor caring for your pregnancy or your baby knows you received this medicine.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Other drugs may affect Andexxa, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

Applies to coagulation factor Xa: intravenous powder for injection

General

The most common adverse reactions (5% or greater) were urinary tract infections and pneumonia.[Ref]

Other

Very common (10% or more): Infusion-related reactions (18%), death prior to day 30 follow-up (14%)

Common (1% to 10%): Sudden death

Frequency not reported: Feeling hot[Ref]

In the ongoing ANNEXA-4 study, there were 25 deaths (14%) prior to the day 30 follow-up visit. The percentage of patients, by bleeding type, who died prior to the day 30 follow-up was: 14% for intracranial bleeding, 10% for gastrointestinal bleeding, and 19% for other bleeding types.[Ref]

Immunologic

Very common (10% or more): Antibodies against this drug (up to 17%)[Ref]

Cardiovascular

Common (1% to 10%): Deep vein thrombosis, acute myocardial infarction, cardiogenic shock, congestive heart failure

Uncommon (0.1% to 1%): Cardiac arrest, cardiac thrombus, iliac artery thrombosis, non-sustained ventricular tachycardia

Frequency not reported: Flushing[Ref]

Respiratory

Common (1% to 10%): Pulmonary embolism, acute respiratory failure

Frequency not reported: Cough, dyspnea, pneumonia[Ref]

Genitourinary

Frequency not reported: Urinary tract infection[Ref]

Dermatologic

Frequency not reported: Mild hives[Ref]

Nervous system

Common (1% to 10%): Ischemic stroke

Uncommon (0.1% to 1%): Embolic stroke

Frequency not reported: Dysgeusia[Ref]

The manufacturer makes no recommendation regarding use during pregnancy.

US FDA pregnancy category: Not assigned

Risk Summary: Insufficient data exists in pregnant women to inform patients of associated risks.

Animal studies have not been reported. There are no controlled data in human pregnancy.

Safety and effectiveness during labor and delivery have not been evaluated.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

General

Factor Xa (recombinant), inactivated-zhzo is available in the following dosage form(s) and strength(s):

Factor Xa (recombinant), inactivated-zhzo is available as a lyophilized powder in single-use vials of 100 mg of coagulation factor Xa (recombinant), inactivated-zhzo. 1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

For intravenous use only after reconstitution.1

• Dose factor Xa (recombinant), inactivated-zhzo based on the specific FXa inhibitor, dose of FXa inhibitor, and time since the patient's last dose of FXa inhibitor. 1

• Administer as an intravenous (IV) bolus, with a target rate of 30 mg/min, followed by continuous infusion for up to 120 minutes.1

• There are two dosing regimens:1

The safety and effectiveness of more than one dose have not been evaluated.

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Inform patients that reversing FXa inhibitor therapy increases the risk of thromboembolic events. Arterial and venous thromboembolic events, ischemic events, cardiac events, and sudden death were observed within 30 days following factor Xa (recombinant), inactivated-zhzo administration.1

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of coagulation factor Xa (recombinant), inactivated-zhzo injection in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of coagulation factor Xa (recombinant), inactivated-zhzo injection in the elderly. However, elderly patients are more sensitive to the effects of this medicine than younger adults.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

A doctor or other trained health professional will give you this medicine in a medical facility. It is given through a needle placed into one of your veins.

Coagulation factor Xa is given as an infusion into a vein. A healthcare provider will give you this injection.

This medicine must be given slowly, and the infusion can take at least 2 hours to complete.

Once your bleeding has been controlled, you may need to begin using anticoagulant medication again to prevent future blood clots. Follow your doctor's instructions very carefully.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Because you will receive coagulation factor Xa in a clinical setting, you are not likely to miss a dose.