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  • CLASSES

    Blood Coagulation Factors

    DEA CLASS

    Rx

    DESCRIPTION

    Antihemophilic factor for the treatment of bleeding episodes in adults with acquired hemophilia A
    Genetically engineered in baby hamster kidney (BHK) cell line
    Porcine factor VIII antibodies can develop

    COMMON BRAND NAMES

    OBIZUR

    HOW SUPPLIED

    OBIZUR Intravenous Inj Pwd F/Sol

    DOSAGE & INDICATIONS

    For the treatment of bleeding episodes in adults with acquired hemophilia A.
    NOTE: The FDA has granted orphan drug status to antihemophilic factor, porcine sequence, recombinant for this indication.
    Intravenous dosage
    Adults

    Initially, 200 units/kg IV. The dose, frequency, 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. Doses may be administered every 4 to 12 hours based on clinical response and measured factor VIII concentration. For minor and moderate bleeding (e.g., superficial muscle without neurovascular compromise, and joint), the circulating factor VIII concentration required is 50% to 100% of normal. For major bleeding (e.g., moderate to severe intramuscular bleeding, retroperitoneal, gastrointestinal, intracranial), the circulating factor VIII concentration required is 100% to 200% of normal to treat an acute bleed and 50% to 100% of normal after the acute bleed is controlled, if needed. Plasma concentration of factor VIII should not exceed 200% of normal or 200 units/dL. Safety and efficacy has not been established in patients with a baseline anti-porcine factor VIII inhibitor titer of more than 20 Bethesda Units (BU).

    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 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 clinical condition.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    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 units. Potency values are determined by a 1-stage clotting assay.
    Each single-use vial nominally contains 500 units per vial. The exact recombinant porcine factor VIII potency in units is stated on each vial.
    Plasma factor VIII concentrations can be monitored using a 1-stage clotting assay.[58255]

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. The solution should be clear and colorless. Do not administer if particulate matter or discoloration are observed.

    Intravenous Administration

    Reconstitution
    Use aseptic technique throughout the entire reconstitution process.
    Allow vial of antihemophilic factor porcine sequence and prefilled diluent syringe (provided) to reach room temperature.
    Peel back the cover of the vial adapter package, taking care not to touch the Luer-lock (tip) in the center of the vial adapter. Do not remove the vial adapter from the plastic package.
    Place the vial adapter package on a clean surface with the Luer-lock pointing up.
    Snap off the tamper-resistant cap of the prefilled syringe.
    While firmly holding the vial adapter package, connect the prefilled syringe to the vial adapter by pushing the syringe tip down onto the Luer-lock in the center of the vial adapter. Turn clockwise until the syringe is secured. Do not over tighten.
    Remove plastic package.
    Place the antihemophilic factor porcine sequence vial on a clean, flat, hard surface. Place the vial adapter over the vial and firmly push the filter spike of the vial adapter through the center of the antihemophilic factor porcine sequence vial's rubber circle until the clear plastic cap snaps onto the vial.
    Push the plunger down to slowly inject all the diluent from the syringe into the vial.
    Gently swirl, in a circular motion, the antihemophilic factor porcine sequence vial without removing the syringe until all of the powder is fully dissolved.
    With 1 hand, hold the vial and adapter, and with the other hand firmly grasp the barrel of the prefilled syringe and in a counterclockwise motion, unscrew the syringe from the vial adapter.
    Storage: Use the reconstituted solution within 3 hours after reconstitution when stored at room temperature.[58255]
     
    Intermittent IV infusion
    Once all vials have been reconstituted, attach a large syringe to the vial adapter by gently pushing the syringe tip down onto the Luer-lock in the center of the vial adapter, turning clockwise until it is securely in place.
    Invert the vial; push the air in the syringe into the vial and withdraw the reconstituted solution into the syringe.
    Unscrew the large syringe counterclockwise from the vial adapter, and repeat this process for all reconstituted vials until the total volume to be administered is reached.
    Do not administer in the same tubing with other medications.
    Administer intravenously at a rate of 1 to 2 mL/minute.[58255]

    STORAGE

    OBIZUR:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Do not freeze
    - Protect from light
    - Reconstituted product should be used within 3 hours
    - Refrigerate (between 36 and 46 degrees F)
    - Store in original container

    CONTRAINDICATIONS / PRECAUTIONS

    Hamster protein hypersensitivity

    Antihemophilic factor, porcine sequence, recombinant is contraindicated in patients who have had life-threatening hypersensitivity reactions to antihemophilic factor, porcine sequence, recombinant or its components, including trace amounts of hamster proteins (hamster protein hypersensitivity).

    Factor VIII inhibitors

    Factor VIII inhibitors may develop in patients receiving antihemophilic factor, porcine sequence, recombinant. All patients should be monitored for the development of porcine 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, porcine sequence. If such antibodies are suspected and there is a lack of clinical response, other therapeutic options should be considered. In a clinical study, patients were considered to have developed porcine factor VIII inhibitors if the titer was >= 0.6 Bethesda Units (BU)/mL. The safety and efficacy of antihemophilic factor, porcine sequence, recombinant has not been established in patients with a baseline antiporcine factor VIII inhibitor titer of > 20 BU/mL. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. The incidence of antibody positivity may be influenced by various factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease; therefore, comparison of incidence of antibodies to recombinant factor VIII porcine sequence with the incidence of antibodies to other products may be misleading.

    Pregnancy

    Antihemophilic factor, porcine sequence, recombinant is classified as FDA pregnancy category C. It is not known whether antihemophilic factor, porcine sequence can cause fetal harm when administered to a pregnant woman. Antihemophilic factor porcine sequence should be administered to a pregnant woman only if clearly needed.

    Breast-feeding

    According to the manufacturer, it is not known whether antihemophilic factor, porcine sequence, recombinant is excreted in breast milk. Because many drugs are excreted in breast milk, caution should be used if administering antihemophilic factor porcine sequence to a breast-feeding woman. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    ADVERSE REACTIONS

    Severe

    anaphylactoid reactions / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known

    Moderate

    antibody formation / Delayed / 5.0
    hypotension / Rapid / Incidence not known
    dyspnea / Early / Incidence not known
    wheezing / Rapid / Incidence not known

    Mild

    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 recombinant antihemophilic factor, porcine sequence, and use caution if administered concomitantly.

    PREGNANCY AND LACTATION

    Pregnancy

    Antihemophilic factor, porcine sequence, recombinant is classified as FDA pregnancy category C. It is not known whether antihemophilic factor, porcine sequence can cause fetal harm when administered to a pregnant woman. Antihemophilic factor porcine sequence should be administered to a pregnant woman only if clearly needed.

    According to the manufacturer, it is not known whether antihemophilic factor, porcine sequence, recombinant is excreted in breast milk. Because many drugs are excreted in breast milk, caution should be used if administering antihemophilic factor porcine sequence to a breast-feeding woman. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Patients with acquired hemophilia A have normal factor VIII genes but develop autoantibodies (i.e., inhibitors) against endogenous factor VIII. The autoantibodies neutralize circulating human factor VIII, resulting in a deficiency of this procoagulant protein. Patients with acquired hemophilia A have a prolonged clotting time, measured by aPTT, a conventional in vitro test for biological activity of factor VIII. Administration of recombinant antihemophilic factor, porcine sequence temporarily replaces the inhibited factor VIII needed for effective hemostasis and normalizes the aPTT over the effective dosing period. However, factor VIII activity, not aPTT, should not be used as a measure of efficacy during treatment.

    PHARMACOKINETICS

    Antihemophilic factor, porcine sequence, recombinant is administered intravenously. Pharmacokinetics were studied in 3 patients with hemophilia A and a history of human factor VIII inhibitors receiving a single antihemophilic factor, porcine sequence, recombinant dose of 100 units/kg. Utilizing the one-stage clotting assay, the mean (standard deviation) for Cmax was 176 (88) units/dl, Tmax was 0.6 (0.03) hours, and half-life was 10.63 (0.77) hours.