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  • CLASSES

    Blood Coagulation Factors

    DEA CLASS

    Rx

    DESCRIPTION

    Fully recombinant, fusion protein with factor IX linked to albumin
    For the control and prevention of bleeding, management of surgical bleeding, and prophylaxis of bleeding episodes in patients with hemophilia B
    Linking to recombinant albumin extends the half-life of factor IX

    COMMON BRAND NAMES

    IDELVION

    HOW SUPPLIED

    IDELVION Intravenous Inj Pwd F/Sol

    DOSAGE & INDICATIONS

    For the prevention and control of hemorrhage in patients with hemophilia B (congential factor IX deficiency or Christmas disease).
    Intravenous dosage
    Adults, Adolescents, Children, Infants, and Neonates

    Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition. Generally, 1 International Unit/kg increases the circulating level of factor IX by 1.3 International Units/dL in patients 12 years and older and by 1 International Units/dL in patients less than 12 years. Dose adjustments may be necessary in pediatric patients; young children may need higher and/or more frequent dosing than calculated dosages. Carefully monitor clinical effects and adjust dosage and/or frequency as needed. Specific neonatal dosing is not provided in the FDA-approved product labeling. For minor or moderate bleeding (e.g., uncomplicated hemarthrosis, muscle bleeding (except iliopsoas), oral bleeding), the circulating factor IX activity required is 30 to 60%. A single infusion should be sufficient; repeat dose as needed every 48 to 72 hours until bleeding stops and healing is achieved. For major bleeding (e.g., life or limb threatening hemorrhage, deep muscle bleeding, including iliopsoas, intracranial, retropharyngeal), the circulating factor IX activity required is 60 to 100%. Repeat dose every 48 to 72 hours for 7 to 14 days, until bleeding stops and healing is achieved; administer maintenance dose weekly. The following formulas may be used to estimate the required dose or the in vivo peak increase in factor IX concentration: Dose (International Units) = Body weight (kg) x Desired factor IX Rise (International Units/dL or % of normal) x (Reciprocal of Recovery [International Units/dL per International Units/kg]) or Estimated Increment of factor IX (International Units/dL or % of normal) = Dose (International Units) x Recovery (International Units/dL per International Unit/kg)/Body Weight (kg).

    For the perioperative management of surgical bleeding in patients with hemophilia B.
    Intravenous dosage
    Adults, Adolescents, Children, Infants, and Neonates

    Dose and duration of treatment depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition. Generally, 1 International Unit/kg increases the circulating level of factor IX by 1.3 International Units/dL in patients 12 years and older and by 1 International Units/dL in patients less than 12 years. Dose adjustments may be necessary in pediatric patients; young children may need higher and/or more frequent dosing than calculated dosages. Carefully monitor clinical effects and adjust dosage and/or frequency as needed. Specific neonatal dosing is not provided in the FDA-approved product labeling. For minor surgery (e.g., uncomplicated tooth extraction), the circulating factor IX activity required is 50 to 80%. A single infusion should be sufficient; repeat dose as needed every 48 to 72 hours until healing is achieved. For major surgery (e.g., intracranial, pharyngeal, retropharyngeal, retroperitoneal), the circulating factor IX activity required is 60 to 100% (initial concentration). Repeat dose every 48 to 72 hours for 7 to 14 days or until bleeding stops and healing is achieved; administer maintenance dose 1 to 2 times per week. The following formulas may be used to estimate the required dose or the in vivo peak increase in factor IX concentration: Dose (International Units) = Body weight (kg) x Desired factor IX Rise (International Units/dL or % of normal) x (Reciprocal of Recovery [International Units/dL per International Units/kg]) or Estimated Increment of factor IX (International Units/dL or % of normal) = Dose (International Units) x Recovery (International Units/dL per International Unit/kg)/Body Weight (kg).

    For routine bleeding prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia B.
    Intravenous dosage
    Adults, Adolescents, and Children 12 years and older

    25 to 40 International Units/kg IV every 7 days. Patients who are well-controlled on this regimen may be switched to 50 to 75 International Units/kg IV every 14 days. Dose adjustments may be necessary in pediatric patients; young children may need higher and/or more frequent dosing than calculated dosages. Carefully monitor clinical effects and adjust dosage and/or frequency as needed.

    Neonates, Infants, and Children less than 12 years

    40 to 55 International Units/kg IV every 7 days. Dose adjustments may be necessary in pediatric patients; young children may need higher and/or more frequent dosing than calculated dosages. Carefully monitor clinical effects and adjust dosage and/or frequency as needed. Specific neonatal dosing is not provided in the FDA-approved product labeling.

    MAXIMUM DOSAGE

    Adults

    Individualize dosage based on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition.

    Geriatric

    Individualize dosage based on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition.

    Adolescents

    Individualize dosage based on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition.

    Children

    Individualize dosage based on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition.

    Infants

    Individualize dosage based on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition.

    Neonates

    Individualize dosage based on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Factor IX is expressed in International Units. Factor IX albumin fusion protein potency is assigned using an in vitro, activated partial thromboplastin time (aPTT)-based, one-stage clotting assay calibrated against the World Health Organization (WHO) International Standard for factor IX concentrates.
    The actual potency per vial of Factor IX is stated on each vial.
    To ensure the desired factor IX activity concentration has been achieved, monitoring of factor IX activity by the one-stage clotting assay is recommended. Factor IX activity measurements in the clinical laboratory may be affected by the type of aPTT reagent or reference standard used.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Reconstitution:
    Use aseptic technique and a flat work surface throughout the entire reconstitution process.
    Allow vials of factor IX albumin fusion protein and diluent (provided) to reach room temperature.
    Remove flip caps from factor IX albumin fusion protein and diluent vials. Sterilize stoppers with provided alcohol swab, and allow to dry.
    Open the Mix2Vial package by peeling away the lid, but do not remove the device from the package.
    Place diluent vial on a flat surface, and hold the vial tightly. Grip the Mix2Vial transfer set together with the clear package and push the plastic spike at the blue end of the Mix2Vial transfer set firmly through the center of the stopper of the diluent vial.
    Remove the clear package from the Mix2Vial transfer set, but do not remove the Mix2Vial transfer set or touch the exposed end of the device.
    Invert the diluent vial with the Mix2Vial transfer set attached, and push the plastic spike of the transparent adapter firmly through the center of the stopper of the factor IX albumin fusion protein vial. The diluent will automatically transfer.
    With the diluent and medication vial still attached, gently swirl the vial to ensure the powder is fully dissolved. Do not shake the vial. The reconstituted solution should be clear or yellow to colorless solution. Do not use the reconstituted solution if it contains particulate matter or is discolored.
    With one hand, grasp the factor IX albumin fusion protein side of the Mix2Vial transfer set, and with the other hand, grasp the blue diluent side of the Mix2Vial transfer set. Unscrew the 2 pieces.
    Draw air into an empty, sterile syringe. While the factor IX albumin fusion protein vial is upright, screw the syringe to the Mix2Vial transfer set and inject air into the vial.
    While keeping the syringe plunger pressed, invert the system upside down and draw the concentrate into the syringe by pulling the plunger back slowly.
    Disconnect the filled syringe by unscrewing it from the Mix2Vial transfer set.
    If the dose requires more than one vial, use a separate, unused Mix2Vial transfer set and diluent vial for each factor IX albumin fusion protein vial. The contents of multiple vials may be pooled into 1 syringe.
    Storage: Use immediately or within 4 hours of reconstitution. Store reconstituted solution at room temperature. Do not refrigerate.
    Intermittent IV infusion:
    Attach the syringe to a sterile infusion set.
    Do not mix or administer in the same tubing or container with other medications.
    Administer via intravenous bolus infusion at a rate of administration determined by the patient's comfort level, and no faster than 10 mL/minute.

    STORAGE

    IDELVION:
    - Do not freeze
    - Protect from light
    - Store between 36 to 77 degrees F
    - Store in original container

    CONTRAINDICATIONS / PRECAUTIONS

    Hamster protein hypersensitivity

    Factor IX albumin fusion protein is contraindicated in patients who have had life-threatening hypersensitivity reactions to factor IX albumin fusion protein or its components, including hamster proteins (hamster protein hypersensitivity). Factor IX albumin fusion protein contains trace amounts of Chinese hamster ovary (CHO) proteins. Patients treated with this product may develop hypersensitivity to these non-human mammalian proteins.

    Pregnancy

    There are no data with the use of factor IX albumin fusion protein in pregnant women to inform a drug-associated risk. Animal studies have not been conducted. It is not known whether factor IX albumin fusion protein can cause fetal harm or affect reproduction capacity when given during pregnancy. Factor IX albumin fusion protein should be administered to a pregnant woman only if clearly needed.

    Breast-feeding

    There are no data on the presence of factor IX albumin fusion protein in human milk, the effects on breast-fed infants, or the effects on milk production. Consider the benefits of breast-feeding along with the mother's clinical need for factor IX albumin fusion protein and any potential adverse effects on the breast-fed infant from factor IX albumin fusion protein or the underlying maternal condition.

    Factor IX inhibitors

    Factor IX inhibitors (neutralizing antibodies) may develop in patients receiving factor IX albumin fusion protein, recombinant. Patients with factor IX inhibitors may be at increased risk of hypersensitivity-type reactions, including anaphylaxis, especially during early phases of treatment. These patients may also be at increased risk for anaphylaxis upon subsequent challenge with factor IX albumin fusion protein. Patients experiencing allergic reactions should be evaluated for the presence of inhibitors. The presence of inhibitors should also be suspected if the expected factor IX activity concentrations in plasma are not attained, or if bleeding is not controlled with the recommended dose of factor IX albumin fusion protein.

    Thromboembolic disease

    Use factor IX albumin fusion protein with caution in patients with thromboembolic disease. The use of factor IX products has been associated with the development of thromboembolic complications (e.g., pulmonary embolism, venous thrombosis, and arterial thrombosis). Monitor for early signs of thromboembolism and consumptive coagulopathy when administering factor IX albumin fusion protein to patients with liver disease, fibrinolysis, perioperative status, or risk factors for thromboembolic events or disseminated intravascular coagulation.

    ADVERSE REACTIONS

    Severe

    nephrotic syndrome / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known

    Moderate

    antibody formation / Delayed / Incidence not known
    hypotension / Rapid / Incidence not known
    wheezing / Rapid / Incidence not known
    dyspnea / Early / Incidence not known

    Mild

    headache / Early / 1.8-1.8
    rash (unspecified) / Early / 0.9-0.9
    dizziness / Early / 0.9-0.9
    urticaria / Rapid / Incidence not known

    DRUG INTERACTIONS

    Aminocaproic Acid: (Major) In general, aminocaproic acid should not be administered simultaneously with factor IX complex, factor IX concentrates, factor IX Fc fusion protein, recombinant, and factor IX albumin fusion protein, recombinant due to the increased risk of thrombosis. Some hematologists recommend separating administration of aminocaproic acid from these clotting factor complexes by 8 hours. Aminocaproic acid has been used concurrently with human factor IX complexes or anti-inhibitor coagulant complex perioperatively in hemophiliac patients. The risk of developing thrombosis, however, is increased. In rare instances, thrombosis leading to acute myocardial infarction or gangrene has been reported in patients with hemophilia receiving combination therapy with factor IX concentrate and aminocaproic acid. Concomitant administration of aminocaproic acid with purer formulations of factor IX may also result in an increased risk of thrombosis.
    Factor VIIa, Recombinant: (Major) The risk of a potential interaction between factor VIIa, recombinant, and factor IX replacement products has not been adequately evaluated. Simultaneous use of these products should be avoided due to the potential for increased risk of thrombosis.
    Tranexamic Acid: (Major) Tranexamic acid should not be administered concomitantly with factor IX complex, Factor IX Fc fusion protein, recombinant, or Factor IX concentrates, due to the increased risk of thrombosis.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no data with the use of factor IX albumin fusion protein in pregnant women to inform a drug-associated risk. Animal studies have not been conducted. It is not known whether factor IX albumin fusion protein can cause fetal harm or affect reproduction capacity when given during pregnancy. Factor IX albumin fusion protein should be administered to a pregnant woman only if clearly needed.

    There are no data on the presence of factor IX albumin fusion protein in human milk, the effects on breast-fed infants, or the effects on milk production. Consider the benefits of breast-feeding along with the mother's clinical need for factor IX albumin fusion protein and any potential adverse effects on the breast-fed infant from factor IX albumin fusion protein or the underlying maternal condition.

    MECHANISM OF ACTION

    Factor IX is a vitamin K-dependent clotting factor that is synthesized in the liver. In patients with hemophilia B there is a deficiency in functional coagulation factor IX leading to a prolonged clotting time in the activated partial thromboplastin time (aPTT) assay. Factor IX albumin fusion protein is a fully recombinant, fusion protein that increases plasma levels of factor IX and can temporarily correct the coagulation defect needed for effective hemostasis. Factor IX albumin fusion protein is comprised of genetically fused recombinant coagulation factor IX and recombinant albumin. Fusion with recombinant albumin extends the half-life of factor IX.

    PHARMACOKINETICS

    Recombinant factor IX albumin fusion protein is administered intravenously. Pharmacokinetic (PK) parameters were based on plasma factor IX activity measured by the one-stage clotting assay. PK parameters following single or repeat dosing for up to 30 weeks were similar. Mean PK data from an analysis of 7 subjects administered a single 25 International Units/kg IV injection describe a half-life (t1/2) of 118 hours, Cmax of 41.1 International Units/dL, AUC0-inf of 4658 hours x International Units/dL, body weight-adjusted clearance (CL) of 0.57 mL/kg/hour, time to 1% factor IX activity of 22 days, time to 3% factor IX activity of 14 days, time to 5% factor IX activity of 10 days, and incremental recovery (IR) of 1.65 International Units/dL per International Units/kg. Mean PK data following a 50 International Units/kg IV injection (n = 47) describe a t1/2 of 104 hours, Cmax of 66.6 International Units/dL, AUC0-inf of 7482 hours x International Units/dL, CL of 0.73 mL/kg/hour, time to 1% factor IX activity of 23 days, time to 3% factor IX activity of 17 days, time to 5% factor IX activity of 13 days, and IR of 1.3 International Units/dL per International Units/kg. Mean PK data from an analysis of 8 subjects administered a single 75 International Units/kg IV injection describe a t1/2 of 104 hours, Cmax of 82 International Units/dL, AUC0-inf of 9345 hours x International Units/dL, CL of 0.84 mL/kg/hour, time to 1% factor IX activity of 25 days, time to 3% factor IX activity of 18 days, time to 5% factor IX activity of 15 days, and IR of 1.08 International Units/dL per International Units/kg.