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  • CLASSES

    Blood Coagulation Factors

    DEA CLASS

    Rx

    DESCRIPTION

    Heat-treated, lyophilized coagulation factor XIII concentrate made from pooled human plasma
    Approved for the prevention of bleeding episodes in patients with congenital factor XIII deficiency.
    Serious hypersensitivity reactions may occur

    COMMON BRAND NAMES

    Corifact

    HOW SUPPLIED

    Corifact Intravenous Inj Pwd F/Susp

    DOSAGE & INDICATIONS

    For routine bleeding prophylaxis in patients with congenital factor XIII deficiency.
    NOTE: Factor XIII concentrate has not been proven to have a direct benefit on the treatment of bleeding episodes.
    NOTE: Dosage is based on patient weight, laboratory values, and the patient's overall clinical condition.
    Intravenous dosage
    Adults, Adolescents, Children, Infants, and Neonates

    40 International Units/kg IV initially. Subsequent dosing should occur every 28 days to maintain a factor XIII activity level trough of approximately 5—20%. Dosage adjustments should be guided by a specific assay used to determine the most recent factor XIII activity level trough (e.g., Berichrom activity assay) and the patient's clinical condition. An example of dosage adjustments using the Berichrom activity assay is as follows: 1 trough level of < 5%, increase dosage by 5 units/kg; trough level of 5—20%, no change in dosage; 2 trough levels of > 20% or 1 trough level of > 25%, decrease dosage by 5 units/kg.

    MAXIMUM DOSAGE

    Specific maximum dosage information is not available. Individualize dosage based on body weight, laboratory values, and the clinical status of the patient.

    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

    Injectable Administration

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

    Intravenous Administration

    For intravenous use only.
    The units of factor XIII concentrate vary between cartons; check the vial to be used for actual factor XIII concentrate content.
    Factor XIII concentrate contains no preservative; use aseptic technique during preparation and administration.
     
    Reconstitution
    The factor XIII vial and diluent vial must be at room temperature prior to reconstitution.
    Remove flip caps of the factor XIII concentrate vial and diluent vial, swab with alcohol, and allow time to dry.
    Open the Mix2Vial transfer set supplied by the manufacturer by peeling away the lid, but keep the transfer set in the clear package.
    Tightly hold the diluent vial on a flat surface and push the plastic spike at the blue end of the Mix2Vial transfer set through the center of the diluent vial, and then carefully remove the clear package from the Mix2Vial (do not pull the transfer set).
    Invert the diluent vial with Mix2Vial transfer set attached and push the plastic spike of the transparent adapter through the center stopper of the factor XIII concentrate vial; the diluent will automatically transfer to the factor XIII concentrate vial.
    Gently swirl the vial to ensure that the product is completely dissolved. Do not shake.
    After reconstitution, the solution should be colorless to slightly yellow and opalescent. Do not use if the product contains particulates.
    Unscrew the diluent vial from the factor XIII concentrate vial. Withdraw appropriate volume into an empty, sterile syringe for administration.
    If the same patient is to receive more than one vial, the contents of multiple vials may be pooled; however, a separate, unused Mix2Vial transfer set must be used for each vial.
    Storage: After reconstitution, the product must be used within 4 hours; do not refrigerate or freeze. Discard any unused portion.
     
    Intravenous injection:
    Administer via a separate infusion line; do not mix with any other intravenous solution or medical product.
    Administer at room temperature by slow intravenous injection at a rate not exceeding 4 mL/min.
    Record the batch number in the patient's medical record.

    STORAGE

    Corifact:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Do not freeze reconstituted product
    - Do not refrigerate reconstituted product
    - May be stored at room temperature not exceeding 77 degrees F for up to 6 months
    - Protect from light
    - Reconstituted product must be used within 4 hours
    - Store in original container
    - Store unreconstituted product in refrigerator (36 to 46 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Factor XIII concentrate is contraindicated for use by patients with known anaphylactic or severe systemic reactions to human plasma-derived products or to any component of the product. Signs and symptoms of hypersensitivity reactions may include urticaria, chest tightness, rash, wheezing, hypotension, and anaphylaxis during or after factor XIII concentrate receipt. Immediately discontinue Factor XIII concentrate administration and initiate appropriate treatment if a hypersensitivity reaction occurs.
     
    The safety and efficacy of Factor XIII has not been established in geriatric patients due to an insufficient number of patients studied.

    Thromboembolic disease

    Thrombotic events have been reported in postmarketing surveillance of Factor XIII concentrate. Monitor patients with known risk factors for thrombotic events, such as patients with thromboembolic disease and pregnant women.

    Infection

    Factor XIII concentrate is derived from human plasma and, therefore, may contain infectious agents such as viruses, and, theoretically, the Creutzfeldt-Jakob disease agent. There is also the possibility that other unknown infectious agents may be present in the product. The risk of infection has been minimized with screening of potential plasma donors, testing for the presence of viruses/infectious agents, and inactivating/removing certain viruses. Human plasma used in the production of Factor XIII concentrate is purified by a combination of precipitation/adsorption, ion exchange chromatography, and heat-treatment procedures. Discuss the risks and benefits of the product with the patient before treatment initiation. Consider vaccination against hepatitis A and B virus for patients who will regularly receive Factor XIII concentrate. Report any infection thought to have been possibly transmitted by Factor XIII concentrate to the CSL Behring Pharmacovigilance Department at 1—866—915—6958 or to the FDA at 1—800—FDA—1088 or www.fda.gov/medwatch.

    Labor, obstetric delivery, pregnancy

    Factor XIII concentrate is classified as FDA pregnancy category C. Thromboembolic events have been reported during post-marketing use of factor XIII concentrate. Because pregnant women are at an increased risk of thromboembolic events, factor XIII should only be administered to a pregnant woman if clearly needed. Factor XIII concentrate has not been studied during labor and obstetric delivery.

    Breast-feeding

    It is not known whether factor XIII concentrate is excreted in human milk. 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.

    Factor XIII inhibitors

    Inhibitory antibodies to factor XIII have been detected in patients receiving factor XIII concentrate. If plasma factor XIII activity concentrations are not achieved or if breakthrough bleeding occurs while on therapy, factor XIII inhibitors may have developed. Prescribers should perform an assay that measures factor XIII antibody concentration.

    ADVERSE REACTIONS

    Severe

    epistaxis / Delayed / 2.0
    anaphylactoid reactions / Rapid / Incidence not known
    thromboembolism / Delayed / Incidence not known
    thrombosis / Delayed / Incidence not known

    Moderate

    erythema / Early / 1.0
    hematoma / Early / 2.0
    elevated hepatic enzymes / Delayed / 1.0
    dyspnea / Early / Incidence not known
    antibody formation / Delayed / Incidence not known

    Mild

    pruritus / Rapid / 1.0
    fever / Early / 2.0
    chills / Rapid / 1.0
    rash / Early / 2.0
    diarrhea / Early / 2.0
    vomiting / Early / 2.0
    abdominal pain / Early / 2.0
    infection / Delayed / 2.0
    headache / Early / 2.0
    arthralgia / Delayed / 2.0
    nausea / Early / Incidence not known

    DRUG INTERACTIONS

    Factor VIIa, Recombinant: (Major) The risk of potential interaction between factor VIIa, recombinant and coagulation factor concentrates has not been adequately evaluated. Simultaneous use of factor VIIa, recombinant and factor XIII concentrate should be avoided due to the potential for thrombosis.

    PREGNANCY AND LACTATION

    Pregnancy

    It is not known whether factor XIII concentrate is excreted in human milk. 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

    Factor XIII is an endogenous plasma glycoprotein that circulates in the blood and is found in platelets, macrophages, and monocytes. Factor XIII is a proenzyme that becomes activated in the presence of calcium to Factor XIIIa. During the coagulation cascade, Factor XIIIa promotes cross-linking of fibrin and is essential in the protection of the clot against fibrinolysis and degradation by plasmin.

    PHARMACOKINETICS

    Factor XIII concentrate is administered intravenously. Pharmacokinetic parameters were determined based on data from 14 patients ranging in age from 5—42 years (9 adults, 2 adolescents, and 3 children). Each patient received 40 units/kg IV every 28 days for a total of 3 doses. The doses were administered at a rate of approximately 250 units/min. After the third dose, the mean increase in Factor XIII activity levels was 83% (range 48—114%) over baseline. The mean half-life was 6.6 +/- 2.29 days and time to peak plasma concentration (Tmax) was achieved in 1.7 +/- 1.44 hours. An increase in Factor XIII plasma concentrations was seen for approximately 28 days.