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  • CLASSES

    Blood Coagulation Factors

    DEA CLASS

    Rx

    DESCRIPTION

    Recombinant, fusion protein with antihemophilic factor linked to the Fc protein fragment of human IgG1
    Used for the control and prevention of bleeding, management of surgical bleeding, and prophylaxis of bleeding episodes in patients with hemophilia A
    Linking to the Fc protein prolongs factor circulation and allows for extended time between prophylactic infusions

    COMMON BRAND NAMES

    ELOCTATE

    HOW SUPPLIED

    Antihemophilic Factor VIII (Recombinant), Fc Fusion Protein/ELOCTATE Intravenous Inj Pwd F/Sol

    DOSAGE & INDICATIONS

    For the management of hemophilia A (congenital Factor VIII deficiency).
    For the control and prevention of bleeding.
    Intravenous dosage
    Adults, Adolescents, Children, Infants, and Neonates

    Dose and duration of treatment depend on the severity of the factor VIII deficiency, the location and extent of bleeding, and the patient’s clinical condition. For minor or moderate bleeding (e.g., joint, superficial muscle (except iliopsoas) without neurovascular compromise, deep laceration and renal, superficial soft tissue, mucous membranes), the circulating factor VIII activity required is 40 to 60%. The dose is 20 to 30 International Units/kg/dose IV every 24 to 48 hours or every 12 to 24 hours for patients less than 6 years of age; continue until bleeding is resolved. For major bleeding (e.g., life- or limb-threatening hemorrhage, iliopsoas and deep muscle with neurovascular injury, retroperitoneal, intracranial, or gastrointestinal), the circulating factor VIII activity required is 80 to 100%. The dose is 40 to 50 International Units/kg/dose IV every 12 to 24 hours or every 8 to 24 hours for patients less than 6 years of age; continue until bleeding is resolved (approximately 7 to 10 days).

    Intravenous dosage
    Adults, Adolescents, Children, Infants, and Neonates

    Generally, 1 International Unit/kg increases the circulating level of factor VIII by 2 International Units/dL. Dose adjustments may be necessary in pediatric patients less than 6 years of age; 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. The following formulas may be used to estimate the required dose or the desired in vivo peak increase in factor VIII concentration: Dose (International Units) = Body Weight (kg) x Desired factor VIII Rise (International Units/dL or % of normal) x 0.5 (International Units/kg per International Units/dL) or Estimated Increment of factor VIII (International Units/dL or % of normal) = [Total Dose (International Units)/Body Weight (kg)] x 2 (International Units/dL per International Units/kg).

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

    Dose and duration of treatment depend on the severity of the factor VIII deficiency, the location and extent of bleeding, and the patient's clinical condition. For minor surgery (e.g., uncomplicated dental extraction), the circulating factor VIII activity required is 50 to 80%. The dose is 25 to 40 International Units/kg/dose IV every 24 hours or every 12 to 24 hours for patients less than 6 years of age; continue for at least 1 day until wound healing is achieved. For major surgery (e.g., intracranial, intra-abdominal, or joint replacement surgery), the circulating factor VIII activity required is 80 to 120%. The preoperative dose is 40 to 60 International Units/kg/dose IV. Postoperatively, 40 to 50 International Units/kg/dose IV after after 8 to 24 hours or after 6 to 24 hours for patients less than 6 years of age. Repeat every 24 hours until adequate wound healing and then continue for at least 7 days to maintain a factor VIII activity within the target range.

    For routine bleeding prophylaxis to prevent or reduce the frequency of bleeding episodes.
    Intravenous dosage
    Adults, Adolescents, and Children 6 years and older

    Initially, 50 International Units/kg/dose IV every 4 days. Adjust dose based on individual response. The typical dosing range is 25 to 65 International Units/kg/dose IV every 3 to 5 days.

    Neonates, Infants, and Children less than 6 years

    Initially, 50 International Units/kg/dose IV twice weekly. Adjust dose based on individual response. The typical dosing range is 25 to 65 International Units/kg/dose IV every 3 to 5 days, but more frequent and higher doses up to 80 International Units/kg may be needed.

    MAXIMUM DOSAGE

    Adults

    Specific maximum dosage information is not available. Individualize dosage based on the severity of the factor VIII deficiency, the location and extent of bleeding, and the patient’s age and clinical condition.

    Geriatric

    Specific maximum dosage information is not available. Individualize dosage based on the severity of the factor VIII deficiency, the location and extent of bleeding, and the patient’s age and clinical condition.

    Adolescents

    Specific maximum dosage information is not available. Individualize dosage based on the severity of the factor VIII deficiency, the location and extent of bleeding, and the patient’s age and clinical condition.

    Children

    Specific maximum dosage information is not available. Individualize dosage based on the severity of the factor VIII deficiency, the location and extent of bleeding, and the patient’s age and clinical condition.

    Infants

    Specific maximum dosage information is not available. Individualize dosage based on the severity of the factor VIII deficiency, the location and extent of bleeding, and the patient’s age and clinical condition.

    Neonates

    Specific maximum dosage information is not available. Individualize dosage based on the severity of the factor VIII deficiency, the location and extent of bleeding, and the patient’s age and 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 VIII activity is expressed in International Units. Antihemophilic factor Fc fusion protein potency is assigned using a chromogenic substrate assay.
    The actual potency per vial of factor VIII is stated on each vial.
    Plasma factor VIII concentrations can be monitored using either a chromogenic substrate assay or a one stage clotting assay.

    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 vial of antihemophilic factor Fc fusion protein and pre-filled diluent syringe (provided) to reach room temperature.
    Peel back the lid from the vial adapter package. Do not remove the vial adapter from the package or touch the inside of the adapter package.
    Place the vial adapter over the vial. Place the adapter spike directly above the center of the rubber stopper and push the adapter straight down until the spike punctures the center of the vial stopper and is fully inserted. Discard package cover.
    Hold the plunger rod at the circular disk and place the tip of the plunger rod into the end of the syringe. Turn clockwise until it is securely attached. Only use the provided diluent syringe.
    Hold diluent syringe with 1 hand by the ridged part directly under cap with cap pointing up. Do not use if the cap has been removed or is not securely attached. Grasp the cap with the other hand and bend it at a 90° angle until it snaps off. Do not touch the glass tip of the syringe or the inside of the cap.
    Insert the tip of the syringe into the adapter opening and turn the syringe clockwise until it is securely attached to the adapter. Slowly depress the plunger rod to inject all of the diluent into the vial. The plunger rod may rise slightly after this process.
    With the syringe still connected to the adapter, gently swirl the vial until the product is completely dissolved. The final solution should be clear to slightly opalescent and colorless. Do not shake. Do not use the reconstituted solution if it contains visible particles or is cloudy.
    Completely depress the plunger rod. Turn the vial upside-down and slowly pull on the plunger rod to draw the solution into the syringe. Be careful not to pull the plunger rod completely out of the syringe.
    Gently unscrew the syringe from the vial adapter and dispose of the vial with the adapter still attached. Do not touch the syringe tip or the inside of the cap.
    If combining 2 or more vials, leave the vial adapter attached to the vial. Do not detach the diluent syringe or the large luer lock syringe until ready to attach the large luer lock syringe to the next vial (with vial adapter attached). Remove the diluent syringe from the vial adapter by turning it counterclockwise until it is completely detached. Attach a separate, large luer lock syringe by turning clockwise until it is securely in place. Slowly pull on the plunger rod to draw the solution into the syringe. Repeat this pooling procedure with each vial necessary to obtain the required dose.
    Use the reconstituted solution as soon as possible, but no later than 3 hours after reconstitution. Protect from direct sunlight. Do not refrigerate after reconstitution.
     
    Intermittent IV infusion:
    Attach the syringe to the connector end of the infusion set tubing by turning clockwise until it is securely in place. Depress the plunger until all air is removed from the syringe and solution has reached the end of the infusion set tubing. Do not push solution through the needle. Remove the protective needle cover from the infusion set tubing.
    Do not 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 per minute.

    STORAGE

    ELOCTATE:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Do not freeze
    - May be stored at temperatures up to 86 degrees F for up to 6 months
    - Prior to dispensing, store in refrigerator (36 to 46 degrees F)
    - Protect from direct sunlight
    - Protect from light
    - Reconstituted product should be used within 3 hours
    - Store in original package until time of use

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Antihemophilic factor, Fc fusion protein, recombinant is contraindicated in patients who have had life-threatening hypersensitivity reactions to antihemophilic factor, Fc fusion protein, recombinant.

    Factor VIII inhibitors

    Factor VIII inhibitors may develop in patients receiving antihemophilic factor, Fc fusion protein, recombinant. All patients should be monitored for the development of factor VIII inhibitors utilizing appropriate clinical observations and laboratory tests. The presence of inhibitors should be suspected if the expected factor VIII activity concentrations in plasma are not attained or if bleeding is not controlled with the recommended dose of antihemophilic factor, Fc fusion protein.

    Pregnancy

    There are no data regarding antihemophilic factor, Fc fusion protein use in pregnant women to inform a drug-associated risk. Animal reproductive and developmental toxicity studies have not been conducted. In a placental transfer study, antihemophilc factor, Fc fusion protein was detected in murine fetal blood at approximately 1% of the maternal blood concentrations, 3 to 4 hours following a dose of 260 to 650 times the clinical human dose. Antihemophilic factor Fc fusion protein should be administered during pregnancy only if clearly needed. If administered, advise the patient that the risks to the mother and fetus are unknown.

    Breast-feeding

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

    ADVERSE REACTIONS

    Severe

    bradycardia / Rapid / 0.4-0.4
    angioedema / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known

    Moderate

    chest pain (unspecified) / Early / 0.4-0.4
    hypertension / Early / 0.4-0.4
    hypotension / Rapid / 0.4-0.4
    dyspnea / Early / Incidence not known
    wheezing / Rapid / Incidence not known
    antibody formation / Delayed / Incidence not known

    Mild

    rash / Early / 0.9-0.9
    myalgia / Early / 0.9-0.9
    malaise / Early / 0.9-0.9
    arthralgia / Delayed / 0.9-0.9
    headache / Early / 0.9-0.9
    dizziness / Early / 0.4-0.4
    dysgeusia / Early / 0.4-0.4
    abdominal pain / Early / 0.4-0.4
    cough / Delayed / 0.4-0.4
    injection site reaction / Rapid / 0.4-0.4
    pruritus / Rapid / Incidence not known
    urticaria / Rapid / Incidence not known

    DRUG INTERACTIONS

    Emicizumab: (Moderate) There is a possibility for hypercoagulability with concomitant use of emicizumab and antihemophilic factor VIII (recombinant) based on preclinical experiments.
    Factor VIIa, Recombinant: (Major) The risk of potential interaction between factor VIIa, recombinant and coagulation factor concentrates has not been adequately evaluated. Simultaneous administration of factor VIIa with prothrombin complex concentrates is not recommended due to the increased risk for thrombosis. Likewise, it would be prudent to consider the potential for thromboembolic complications with coadministration of factor VIIa, recombinant and antihemophilic factor, Fc fusion protein, and use caution if administer concomitantly.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no data regarding antihemophilic factor, Fc fusion protein use in pregnant women to inform a drug-associated risk. Animal reproductive and developmental toxicity studies have not been conducted. In a placental transfer study, antihemophilc factor, Fc fusion protein was detected in murine fetal blood at approximately 1% of the maternal blood concentrations, 3 to 4 hours following a dose of 260 to 650 times the clinical human dose. Antihemophilic factor Fc fusion protein should be administered during pregnancy only if clearly needed. If administered, advise the patient that the risks to the mother and fetus are unknown.

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

    MECHANISM OF ACTION

    In patients with hemophilia A, there is a deficiency of functional coagulation factor VIII leading to a prolonged clotting time in the activated partial thromboplastin time (aPTT) assay. Administration of recombinant antihemophilic factor Fc fusion protein normalizes the aPTT over the effective dosing period. Antihemophilic factor Fc fusion protein is a fully recombinant, fusion protein that temporarily replaces the missing coagulation factor VIII needed for effective hemostasis. Antihemophilic factor Fc fusion protein contains the Fc region of human IgG1, which binds to the neonatal Fc receptor (FcRn). FcRn is part of a naturally occurring pathway that delays lysosomal degradation of immunoglobulins by cycling them back into circulation and prolonging their plasma half-life.

    PHARMACOKINETICS

    Recombinant antihemophilic factor Fc fusion protein is administered intravenously. Pharmacokinetic (PK) data from an analysis of 28 subjects administered a single 10 minute intravenous infusion of 50 International Units/kg describe a half-life of 19.7 hours, Cmax of 109 International Units/dL, AUC/Dose of 54.1 International Units x hour/dL per International Units/kg, time to 1% factor VIII activity of 5.1 days, and incremental recovery of 2.26 International Units/dL per International Units/kg. The PK parameters were based on plasma factor VIII activity measured by the one-stage clotting assay. The PK parameters at week 14, after repeated dosing, were comparable to the PK parameters obtained after the first dose, indicating a prolonged circulating half-life.