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  • CLASSES

    Blood Coagulation Factors

    DEA CLASS

    Rx

    DESCRIPTION

    Clotting factor responsible for increasing the rate of cleavage of factor X by activated factor IX
    For prevention and management of bleeding in patients with hemophilia A; some products also approved in patients with von Willebrand's disease
    Many products available that differ based on purity and source of factor VIII

    COMMON BRAND NAMES

    Advate, Adynovate, AFSTYLA, Alphanate, Helixate FS, Hemofil M, Humate-P, Koate, Koate-DVI, Kogenate FS, Kovaltry, Monoclate-P, Novoeight, Nuwiq, Recombinate, Wilate vonWillebrand, XYNTHA, XYNTHA Solofuse

    HOW SUPPLIED

    Advate/Adynovate/AFSTYLA/Alphanate/Helixate FS/Hemofil M/Humate-P/Koate/Koate-DVI/Kogenate FS/Kovaltry/Monoclate-P/Novoeight/Nuwiq/Recombinate/Wilate vonWillebrand/XYNTHA/XYNTHA Solofuse Intravenous Inj Pwd F/Sol
    Nuwiq Intravenous Pwd

    DOSAGE & INDICATIONS

    For the prevention and control of hemorrhage in patients with hemophilia A (classical hemophilia).
    NOTE: Humate, Kogenate, and ReFacto have been designated by the FDA as orphan drugs for the prophylaxis and management of hemorrhage or hemarthrosis in patients with hemophilia A.

    NOTE: Guidelines for the treatment of acute bleeding and prevention of bleeding during surgery vary. For all indications, the dose of antihemophilic factor should be individualized taking into consideration the seriousness of the bleed or procedure, the clinical status of the patient, and the factor VIII activity concentration.
    For minor bleeding including early muscle bleed, early hemarthrosis, and oral bleeds.
    Intravenous dosage (Advate, Hemofil M, Monarc-M, Recombinate, ReFacto)
    Adults, Adolescents, Children, and Infants

    10 to 20 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 20% to 40% of normal is administered. If bleeding or pain continues, the dose can be repeated every 12 to 24 hours for 1 to 3 days.

    Intravenous dosage (Alphanate)
    Adults, Adolescents, Children, and Infants

    10 to 15 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 20% to 30% of normal is administered; most minor bleeds can be treated with 1 dose.

    Intravenous dosage (Helixate FS, Kogenate FS)
    Adults, Adolescents, Children, and Infants

    10 to 20 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 20% to 40% of normal is administered. If bleeding or pain continues, the dose can be repeated.

    Intravenous dosage (Humate-P)
    Adults, Adolescents, Children, and Infants

    15 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 30% of normal is given; most minor bleeds can be treated with 1 dose. If needed, half of the loading dose may be given 1 to 2 times per day for 1 to 2 days.

    Intravenous dosage (Koate)
    Adults

    15 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 30% of normal; repeat dose every 12 hours until bleeding stops and healing is achieved, typically 1 to 2 days.

    Children and Adolescents

    15 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 30% of normal; repeat dose every 12 hours until bleeding stops and healing is achieved, typically 1 to 2 days.

    Intravenous dosage (Koate-DVI)
    Adults, Adolescents, Children, and Infants

    10 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 20% of normal is administered; the dose may be repeated if there is evidence of continued bleeding.

    Intravenous dosage (Monoclate-P)
    Adults, Adolescents, Children, and Infants

    15 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 30% of normal is given. One dose is usually all that is needed.

    Intravenous dosage (Xyntha)
    Adults

    10 to 20 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 20% to 40% of normal; the dose may be repeated every 12 to 24 hours until resolved and for at least 1 day depending on the severity of the bleeding episode.

    Infants, Children, and Adolescents

    10 to 20 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 20% to 40% of normal; the dose may be repeated every 12 to 24 hours until resolved and for at least 1 day depending on the severity of the bleeding episode.

    Intravenous dosage (Novoeight)
    Adults, Adolescents, Children, Infants

    10 to 20 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 20% to 40% of normal; the dose may be repeated every 12 to 24 hours for at least 1 day and until bleeding is resolved.

    Intravenous dosage (Nuwiq)
    Adults

    10 to 20 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 20% to 40% of normal; repeat the dose every 12 to 24 hours for at least 1 day and until the bleeding episode is resolved.

    Children and Adolescents 2 years and older

    10 to 20 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 20% to 40% of normal; repeat the dose every 12 to 24 hours for at least 1 day and until the bleeding episode is resolved.

    Intravenous dosage (Adynovate)
    Adults

    10 to 20 International Units/kg/dose IV to achieve a target FVIII activity concentration of 20% to 40% of normal; repeat the dose every 12 to 24 hours until bleeding is resolved.

    Children and Adolescents

    10 to 20 International Units/kg/dose IV to achieve a target FVIII activity concentration of 20% to 40% of normal; repeat the dose every 12 to 24 hours until bleeding is resolved.

    Intravenous dosage (Kovaltry)
    Adults, Adolescents, Children, and Infants

    10 to 20 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 20% to 40% of normal; repeat dose every 12 to 24 hours for at least 1 day, until bleeding episode as indicated by pain is resolved or healing is achieved.

    Intravenous dosage (Afstyla)
    Adults, Adolescents, Children, and Infants

    10 to 20 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 20% to 40% of normal; repeat dose every 12 to 24 hours until bleeding episode, as indicated by pain, is resolved or healing achieved.

    For moderate bleeding including advanced muscle bleed, extensive hemarthrosis, hematoma, and mild head trauma.
    Intravenous dosage (Advate, Hemofil M, Monarc-M, Recombinate, ReFacto)
    Adults, Adolescents, Children, and Infants

    15 to 30 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 30% to 60% of normal; repeat every 12 to 24 hours for 3 days or more until bleeding resolves (as indicated by relief of pain or resolution of disability).

    Intravenous dosage (Alphanate)
    Adults, Adolescents, Children, and Infants

    10 to 15 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 20% to 30% of normal. Additional doses may be administered if bleeding recurs.

    Intravenous dosage (Helixate FS/Kogenate FS)
    Adults, Adolescents, Children, and Infants

    15 to 30 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 30% to 60% of normal. An additional dose can be administered after 12 to 24 hours, if needed.

    Intravenous dosage (Humate-P)
    Adults, Adolescents, Children, and Infants

    25 International Units/kg/dose IV to achieve a FVIII activity concentration of approximately 50% of normal, followed by 15 International Units/kg/dose IV every 8 to 12 hours for the first 1 to 2 days to maintain a FVIII activity concentration of about 30% of normal; then continue the same dose 1 to 2 times per day for up to 7 days or until adequate wound healing.

    Intravenous dosage (Koate)
    Adults

    25 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 50% of normal; repeat dose every 12 hours until healing is achieved, typically 2 to 7 days.

    Children and Adolescents

    25 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 50% of normal; repeat dose every 12 hours until healing is achieved, typically 2 to 7 days.

    Intravenous dosage (Koate-DVI, Monoclate-P)
    Adults, Adolescents, Children, and Infants

    15 to 25 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 30% to 50% of normal. If additional treatment is necessary, 10 to 15 International Units/kg/dose IV may be given every 8 to 12 hours.

    Intravenous dosage (Xyntha)
    Adults

    15 to 30 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 30% to 60% of normal; repeat every 12 to 24 hours for 3 to 4 days or until local hemostasis is achieved.

    Infants, Children, and Adolescents

    15 to 30 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 30% to 60% of normal; repeat every 12 to 24 hours for 3 to 4 days or until local hemostasis is achieved.

    Intravenous dosage (Novoeight)
    Adults, Adolescents, Children, and Infants

    15 to 30 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 30% to 60% of normal; repeat every 12 to 24 hours for approximately 3 to 4 days or until pain and acute disability are resolved.

    Intravenous dosage (Nuwiq)
    Adults

    15 to 30 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 30% to 60% of normal; repeat every 12 to 24 hours for 3 to 4 days or until bleeding is resolved.

    Children and Adolescents 2 years and older

    15 to 30 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 30% to 60% of normal; repeat every 12 to 24 hours for 3 to 4 days or until bleeding is resolved.

    Intravenous dosage (Adynovate)
    Adults

    15 to 30 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 30% to 60% of normal; repeat every 12 to 24 hours until bleeding is resolved.

    Children and Adolescents

    15 to 30 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 30% to 60% of normal; repeat every 12 to 24 hours until bleeding is resolved.

    Intravenous dosage (Kovaltry)
    Adults, Adolescents, Children, and Infants

    15 to 30 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 30% to 60% of normal; repeat dose every 12 to 24 hours for 3 to 4 days or more until pain and acute disability are resolved.

    Intravenous dosage (Afstyla)
    Adults, Adolescents, Children, and Infants

    15 to 30 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 30% to 60% of normal; repeat dose every 12 to 24 hours for 3 to 4 days or more until pain and acute disability resolved.

    For life- or limb-threatening bleeding including surgical bleeding, gastrointestinal bleeding, neck, tongue or pharyngeal hematoma with potential for airway compromise, intracranial, intraabdominal, or intrathoracic bleeding, or fractures.
    Intravenous dosage (Advate, Hemofil M, Monarc-M, Recombinate, ReFacto)
    Adults, Adolescents, Children, and Infants

    30 to 50 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 60% to 100% of normal; repeat every 8 to 24 hours until bleeding resolves.

    Intravenous dosage (Alphanate)
    Adults, Adolescents, Children, and Infants

    15 to 25 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 30% to 50% of normal. Doses are generally required twice daily for several days.

    Intravenous dosage (Koate)
    Adults

    40 to 50 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 80% to 100% of normal; repeat dose every 12 hours for at least 3 to 5 days. Then, 25 International Units/kg/dose IV every 12 hours until healing is achieved for up to 10 days. Intracranial hemorrhage may require prophylaxis therapy for up to 6 months.

    Children and Adolescents

    40 to 50 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 80% to 100% of normal; repeat dose every 12 hours for at least 3 to 5 days. Then, 25 International Units/kg/dose IV every 12 hours until healing is achieved for up to 10 days. Intracranial hemorrhage may require prophylaxis therapy for up to 6 months.

    Intravenous dosage (Helixate FS, Kogenate FS, Koate-DVI, Monoclate-P)
    Adults, Adolescents, Children, and Infants

    40 to 50 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 80% to 100% of normal. Repeated doses of 20 to 25 International Units/kg/dose IV to achieve a FVIII activity concentration of 40% to 50% of normal should be administered every 8 to 12 hours.

    Intravenous dosage (Humate-P)
    Adults, Adolescents, Children, and Infants

    40 to 50 International Units/kg/dose IV followed by 20 to 25 International Units/kg/dose IV every 8 hours to maintain FVIII activity concentrations of 80% to 100% of normal for 7 days; then continue the same dose 1 to 2 times per day to maintain the FVIII activity concentration at 30% to 50% of normal for 7 days or until adequate healing.

    Intravenous dosage (Xyntha)
    Adults

    30 to 50 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 60% to 100% of normal; repeat every 8 to 24 hours until bleeding is resolved.

    Infants, Children, and Adolescents

    30 to 50 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 60% to 100% of normal; repeat every 8 to 24 hours until bleeding is resolved.

    Intravenous dosage (Novoeight)
    Adults, Adolescents, Children, and Infants

    30 to 50 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 60% to 100% of normal; repeat every 8 to 24 hours until bleeding is resolved (approximately 7 to 10 days).

    Intravenous dosage (Nuwiq)
    Adults

    30 to 50 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 60% to 100% of normal; repeat every 8 to 24 hours until bleeding is resolved.

    Children and Adolescents 2 years and older

    30 to 50 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 60% to 100% of normal; repeat every 8 to 24 hours until bleeding is resolved.

    Intravenous dosage (Adynovate)
    Adults

    30 to 50 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 60% to 100% of normal; repeat every 8 to 24 hours until bleeding is resolved.

    Children and Adolescents

    30 to 50 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 60% to 100% of normal; repeat every 8 to 24 hours until bleeding is resolved.

    Intravenous dosage (Kovaltry)
    Adults, Adolescents, Children, and Infants

    30 to 50 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 60% to 100% of normal; repeat dose every 8 to 24 hours until bleeding is resolved.

    Intravenous dosage (Afstyla)
    Adults, Adolescents, Children, and Infants

    30 to 50 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 60% to 100% of normal; repeat dose every 8 to 24 hours until bleeding episode is resolved.

    Continuous infusion dosage†
    Adults, Adolescents, Children, and Infants

    50 International Units/kg IV loading dose to achieve a peak post-infusion FVIII activity concentration of 80% to 100% of normal; then 2 International Units/kg/hour continuous IV infusion adjusted based upon the plasma FVIII activity concentrations has been used. For the first 7 days or until bleeding resolves, the goal is a FVIII activity concentration of 80% to 100%. Once bleeding resolves, the rate of the infusion may be decreased to maintain FVIII activity concentrations of 30% to 50% depending upon the clinical status of the patient. A higher rate of infusion of 4 to 5 International Units/kg/hour has also been suggested.

    For bleeding in patients with hemophilia A and factor VIII inhibitor titers less than 10 Bethesda Units and with low anamnestic responses.
    Intravenous dosage (monoclonal antibody-purified or recombinant AHF)
    Adults, Adolescents, Children, and Infants

    The actual dose of recombinant AHF appropriate to treat hemorrhages in patients with low concentrations of inhibitors has not been established. In general, higher doses than those normally required for a particular bleed episode are needed. Doses should be based upon the clinical situation and the inhibitor status of the patient. Initial doses of 50 to 100 International Units/kg IV may be required. Close monitoring of FVIII activity concentrations is needed. Repeat doses as needed until desired FVIII activity concentration is reached, then doses continue every 8 to 12 hours to maintain the FVIII activity in the therapeutic range.

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

    For minor surgical procedures, including tooth extraction, 30 to 50 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 60% to 100% of normal within 1 hour of the procedure. Additional doses every 12 to 24 hours can be given to control bleeding. For dental procedures, adjunctive therapy may be considered. For major surgery, 40 to 60 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 80% to 120% of normal. Doses may be repeated every 8 to 24 hours depending on the desired concentration of Factor VIII and state of wound healing.

    Intravenous dosage (Adynovate)
    Adults

    For minor surgical procedures, including tooth extractions, 30 to 50 International Units/kg/dose IV to achieve a peak post-infusion factor VIII activity concentration of 60% to 100% of normal; repeat every 24 hours as necessary until bleeding is resolved. For major surgery, administer 40 to 60 International Units/kg/dose IV to achieve a peak post-infusion factor VIII activity concentration of 80% to 120% of normal (pre- and post-operative); repeat every 8 to 24 hours until adequate wound healing is achieved and to maintain FVIII activity concentration 80% to 120% of normal.

    Children and Adolescents 12 to 17 years

    For minor surgical procedures, including tooth extractions, 30 to 50 International Units/kg/dose IV to achieve a peak post-infusion factor VIII activity concentration of 60% to 100% of normal; repeat every 24 hours as necessary until bleeding is resolved. For major surgery, administer 40 to 60 International Units/kg/dose IV to achieve a peak post-infusion factor VIII activity concentration of 80% to 120% of normal (pre- and post-operative); repeat every 8 to 24 hours until adequate wound healing is achieved and to maintain FVIII activity concentration 80% to 120% of normal.

    Children 1 to 11 years

    For minor surgical procedures, including tooth extractions, 30 to 50 International Units/kg/dose IV to achieve a peak post-infusion factor VIII activity concentration of 60% to 100% of normal; repeat every 24 hours as necessary until bleeding is resolved. For major surgery, administer 40 to 60 International Units/kg/dose IV to achieve a peak post-infusion factor VIII activity concentration of 80% to 120% of normal (pre- and post-operative); repeat every 6 to 24 hours until adequate wound healing is achieved and to maintain FVIII activity concentration 80% to 120% of normal.

    Intravenous dosage (Afstyla)
    Adults, Adolescents, Children, and Infants

    For minor surgical procedures, including tooth extractions, 15 to 30 International Units/kg/dose IV to achieve a peak post-infusion factor VIII activity concentration of 30% to 60% of normal; repeat every 24 hours for at least 1 day or until healing is achieved. For major surgery, administer 40 to 50 International Units/kg/dose IV to achieve a peak post-infusion factor VIII activity concentration of 80% to 100% of normal; repeat every 8 to 24 hours until adequate wound healing is achieved, then 15 to 30 International Units/kg/dose IV to maintain FVIII activity concentration of 30% to 60% of normal for another 7 days.

    Intravenous dosage (Alphanate)
    Adults, Adolescents, Children, and Infants

    For tooth extraction, 25 International Units/kg/dose IV for a peak post-infusion FVIII activity concentration of 50% of normal is given immediately prior to the procedure; additional doses can be administered if bleeding occurs. For other surgical procedures, including major surgery, 25 to 40 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 50% to 80% of normal; the FVIII activity concentration should be maintained at 30% of normal or higher for approximately 2 weeks.

    Intravenous dosage (Helixate FS, Kogenate FS)
    Adults, Adolescents, Children, and Infants

    For minor surgical procedures, including tooth extraction, 15 to 30 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 30% to 60% of normal. The dose may be repeated in 12 to 24 hours if necessary. For major surgical procedures, 50 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 100% of normal. The dose may be repeated every 6 to 12 hours initially for 10 to 14 days until healing is complete.

    Intravenous dosage (Hemofil-M, Monarc-M, Recombinate)
    Adults, Adolescents, Children, and Infants

    For minor surgical procedures, including tooth extraction, a single infusion of 30 to 40 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 60% to 80% of normal within 1 hour of the procedure is sufficient in approximately 70% of cases; administer in combination with an oral antifibrinolytic agent. For major surgery, 40 to 50 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 80% to 100% of normal. The dose can be repeated every 8 to 24 hours until the threat for bleeding is resolved.

    Intravenous dosage (Humate-P)
    Adults, Adolescents, Children, and Infants

    For tooth extraction, 25 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of approximately 50% of normal, followed by 15 International Units/kg/dose IV every 8 to 12 hours for the first 1 to 2 days to maintain a FVIII activity concentration of about 30%; then continue maintenance dose 1 to 2 times per day for up to 7 days or until adequate wound healing. For major surgery, 40 to 50 International Units/kg/dose IV followed by 20 to 25 International Units/kg/dose IV every 8 hours to maintain FVIII activity concentration of 80% to 100% for 7 days; then continue the dose 1 to 2 times per day to maintain the FVIII activity concentration at 30% to 50% for 7 days or until adequate healing.

    Intravenous dosage (Koate)
    Adults

    40 to 50 International Units/kg/dose IV once to achieve a target factor VIII activity concentration of 80% to 100% of normal prior to surgery. After surgery, 30 to 50 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 50% to 100% of normal; repeat dose every 12 hours for 7 to 10 days or until healing is achieved.

    Children and Adolescents

    40 to 50 International Units/kg/dose IV once to achieve a target factor VIII activity concentration of 80% to 100% of normal prior to surgery. After surgery, 30 to 50 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 50% to 100% of normal; repeat dose every 12 hours for 7 to 10 days or until healing is achieved.

    Intravenous dosage (Koate-DVI)
    Adults, Adolescents, Children, and Infants

    For major surgical procedures, 50 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 100% of normal; repeat every 6 to 12 hours initially for a total of 10 to 14 days until healing is complete. The intensity of the replacement therapy required depends on the type of surgery and postoperative regimen employed. For minor surgical procedures, less intensive treatment schedules may provide adequate hemostasis.

    Intravenous dosage (Kovaltry)
    Adults, Adolescents, Children, and Infants

    For minor surgery (e.g., uncomplicated tooth extraction), 15 to 30 International Units/kg/dose to achieve a peak post-infusion factor VIII concentration of 30% to 60% of normal (pre- and post-operative); repeat dose as needed every 24 hours until healing is achieved. For major surgery (e.g., intracranial, intra-abdominal, intrathoracic, or joint replacement surgery), 40 to 50 International Units/kg/dose to achieve a peak post-infusion factor VIII concentration of 80% to 100% of normal (pre- and post-operative); repeat dose every 8 to 24 hours until wound healing is achieved, then continue therapy for at least another 7 days to maintain factor VIII activity of 30% to 60% of normal.

    Intravenous dosage (Monoclate-P)
    Adults, Adolescents, Children, and Infants

    For minor surgical procedures, 15 to 25 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 30% to 50% of normal; if additional doses are necessary, 10 to 15 International Units/kg/dose IV every 8 to 12 hours can be administered. For major surgery, 40 to 50 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 80% to 100% should be given 1 hour prior to surgery. A second dose, one-half of the priming dose, should be given 5 hours after the first dose. FVIII concentrations should be maintained at a daily minimum of at least 30% for a period of 10 to 14 days postoperatively.

    Intravenous dosage (Novoeight)
    Adults, Adolescents, Children, and Infants

    For minor surgical procedures, including tooth extraction, 15 to 30 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 30% to 60% of normal; repeat dose every 24 hours for at least 1 day and until healing is achieved. For major surgery, 40 to 50 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 80% to 100% of normal; repeat dose every 8 to 24 hours until adequate wound healing is achieved, and then continue therapy for at least 7 days to maintain a FVIII activity concentration of 30% to 60% of normal.

    Intravenous dosage (Nuwiq)
    Adults

    For minor surgical procedures, including tooth extractions, 15 to 30 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 30% to 60% of normal; repeat every 24 hours for at least 1 day or until healing is achieved. For major surgery, administer 40 to 50 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 80% to 100% of normal; repeat every 8 to 24 hours until adequate wound healing is achieved. Once wound healing is achieved, 15 to 30 International Units/kg/dose IV to maintain FVIII activity concentration of 30% to 60% of normal for another 7 days.

    Children and Adolescents 2 years and older

    For minor surgical procedures, including tooth extractions, 15 to 30 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 30% to 60% of normal; repeat every 24 hours for at least 1 day or until healing is achieved. For major surgery, 40 to 50 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 80% to 100% of normal; repeat every 8 to 24 hours until adequate wound healing is achieved. Once wound healing is achieved, 15 to 30 International Units/kg/dose IV to maintain FVIII activity concentration of 30% to 60% of normal for another 7 days.

    Intravenous dosage (ReFacto)
    Adults, Adolescents, Children, and Infants

    For minor surgical procedures, 15 to 30 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 30% to 60% of normal; repeat every 12 to 24 hours for 3 days. For tooth extractions, 1 dose plus an oral antifibrinolytic therapy within 1 hour of the procedure may be sufficient. For major surgery, 30 to 50 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 60% to 100% of normal; repeat every 8 to 24 hours until hemostasis is achieved.

    Intravenous dosage (Xyntha)
    Adults

    For minor surgical procedures, 15 to 30 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 30% to 60% of normal; repeat every 12 to 24 hours for 3 to 4 days or until local hemostasis is achieved. For tooth extractions, 1 dose plus an oral antifibrinolytic therapy within 1 hour of the procedure may be sufficient. For major surgery, 30 to 50 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 60% to 100% of normal; repeat every 8 to 24 hours until hemostasis is achieved.

    Infants, Children, and Adolescents

    For minor surgical procedures, 15 to 30 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 30% to 60% of normal; repeat every 12 to 24 hours for 3 to 4 days or until local hemostasis is achieved. For tooth extractions, 1 dose plus an oral antifibrinolytic therapy within 1 hour of the procedure may be sufficient. For major surgery, administer 30 to 50 International Units/kg/dose IV to achieve a peak post-infusion FVIII activity concentration of 60% to 100% of normal; repeat every 8 to 24 hours until hemostasis is achieved.

    For routine bleeding prophylaxis to reduce the frequency of bleeding episodes in patients with hemophilia A.
    Intravenous dosage (Kogenate FS)
    Adults and Adolescents 17 years and older

    25 International Units/kg IV/dose 3 times per week.

    Infants, Children, and Adolescents 16 years and younger

    25 International Units/kg/dose IV every other day. A total of 65 boys less than 30 months of age with severe hemophilia A and no pre-existing joint damage were observed for up to 5.5 years in a multicenter, open-label, prospective, randomized, controlled clinical study. Patients were randomly assigned to prophylaxis (25 International Units/kg IV every other day) or enhanced episodic therapy (at least 3 doses totaling a minimum of 80 International Units/kg at the time of joint damage). The primary outcome was incidence of bone or cartilage damage detected by MRI. At 6 years of age, 93% of boys in the prophylaxis group and 55% of those in the episodic-therapy group were defined as having normal index-joint structure on MRI (p = 0.006). The relative risk of MRI-detected joint damage with episodic therapy as compared with prophylaxis was 6.1 (95% confidence interval, 1.5 to 24.4). The mean annual numbers of joint and total hemorrhages were higher at study conclusion in the episodic-therapy group than in the prophylaxis group (p < 0.001 for both comparisons).

    Intravenous dosage (Novoeight)
    Adults, Adolescents, and Children 12 years and older

     20 to 50 International Units/kg/dose IV 3 times weekly or 20 to 40 International Units/kg/dose IV every other day.

    Infants and Children younger than 12 years

    25 to 60 International Units/kg/dose IV 3 times weekly or 25 to 50 International Units/kg/dose IV every other day.

    Intravenous dosage (Nuwiq)
    Adults, Adolescents, and Children 12 years and older

    30 to 40 International Units/kg/dose IV every other day.

    Children 2 to 11 years

    30 to 50 International Units/kg/dose IV every other day or 3 times weekly.

    Intravenous dosage (Advate)
    Adults, Adolescents, Children, and Infants

    20 to 40 International Units/kg/dose IV 3 to 4 times weekly or 20 to 40 International Units/kg/dose IV every 3 days to maintain factor VIII trough concentrations 1% or more of normal. Adjust the dose based on clinical response.

    Intravenous dosage (Adynovate)
    Adults

    40 to 50 International Units/kg/dose IV 2 times weekly. Adjust dose based on clinical response.

    Children and Adolescents 12 to 17 years

    40 to 50 International Units/kg/dose IV 2 times weekly. Adjust dose based on clinical response.

    Children 1 to 11 years

    55 to 70 International Units/kg/dose IV 2 times weekly. Adjust dose based on clinical response.

    Intravenous dosage (Kovaltry)
    Adults, Adolescents, and Children older than 12 years

    20 to 40 International Units/kg/dose IV 2 or 3 times weekly. Carefully monitor clinical effects and adjust dosage based on clinical response.

    Infants and Children 12 years and younger

    25 to 50 International Units/kg/dose IV 2 times weekly, 3 times weekly, or every other day.

    Intravenous dosage (Afstyla)
    Adults, Adolescents, and Children 12 years and older

    20 to 50 International Units/kg/dose IV 2 to 3 times weekly. Carefully monitor clinical effects and adjust dosage based on clinical response.

    Infants and Children less than 12 years

    30 to 50 International Units/kg/dose IV 2 to 3 times weekly. Carefully monitor clinical effects and adjust dosage and/or frequency as needed.

    For the management of hemorrhage or hemarthrosis in patients with von Willebrand's disease (vWD).
    NOTE: Humate-P has been designated by the FDA as orphan drugs for this indication.
    For major hemorrhage in patients with mild vWD type I (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma or traumatic hemorrhage).
    Intravenous dosage (Humate-P)
    Adults, Adolescents, Children, and Infants

    40 to 60 International Units vWF:RCo/kg/dose (17 to 24 International Units/kg Humate-P) IV loading dose then 40 to 50 International Units vWF:RCo/kg/dose (17 to 20 International Units/kg Humate-P) IV every 8 to 12 hours for 3 days to keep the nadir concentration of vWF:RCo more than 50%. Continue same dose daily for up to a total of 7 days.

    Intravenous dosage (Wilate)
    Adults, Adolescents, Children, and Infants

    40 to 60 International Units vWF:RCo/kg/dose IV loading dose then 20 to 40 International Units vWF:RCo/kg/dose IV every 12 to 24 hours to keep the nadir concentration of vWF:RCo more than 50%. Therapy may need to be continued for 5 to 7 days.

    For minor hemorrhage in patients with moderate to severe vWD type I, type II, and type III (e.g., epistaxis, oral bleeding, or menorrhagia).
    Intravenous dosage (Humate-P)
    Adults, Adolescents, Children, and Infants

    40 to 50 International Units vWF:RCo/kg/dose (17 to 20 International Units/kg Humate-P) IV for 1 to 2 doses.

    Intravenous dosage (Wilate)
    Adults, Adolescents, Children, and Infants

    20 to 40 International Units vWF:RCo/kg/dose IV loading dose then 20 to 30 International Units vWF:RCo/kg/dose IV every 12 to 24 hours for up to 3 days to keep the nadir concentration of vWF:RCo more than 30%.

    For major hemorrhage in patients with moderate to severe vWD type I (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma, hemarthrosis, or traumatic hemorrhage).
    Intravenous dosage (Humate-P)
    Adults, Adolescents, Children, and Infants

    50 to 75 International Units vWF:RCo/kg/dose (20 to 30 International Units/kg Humate-P) IV loading dose then 40 to 60 International Units vWF:RCo/kg/dose (17 to 24 International Units/kg Humate-P) IV every 8 to 12 hours for 3 days to keep the nadir concentration of vWF:RCo more than 50%. Continue this dose daily for a total of up to 7 days. FVIII concentrations should be monitored and maintained as appropriate (60 to 100%) depending upon the severity of the bleed.

    Intravenous dosage (Wilate)
    Adults, Adolescents, Children, and Infants

    40 to 60 International Units vWF:RCo/kg/dose IV loading dose then 20 to 40 International Units vWF:RCo/kg/dose IV every 12 to 24 hours to keep the nadir concentration of vWF:RCo more than 50%. Therapy may need to be continued for 5 to 7 days.

    For major hemorrhage in patients with vWD type II and III (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma, hemarthrosis, or traumatic hemorrhage).
    Intravenous dosage (Humate-P)
    Adults, Adolescents, Children, and Infants

    60 to 80 International Units vWF:RCo/kg/dose (24 to 32 International Units/kg Humate-P) IV loading dose then 40 to 60 International Units vWF:RCo/kg/dose (17 to 24 International Units/kg Humate-P) IV every 8 to 12 hours for 3 days to keep the nadir concentration of vWF:RCo more than 50%. Continue this dose daily for a total of up to 7 days. FVIII concentrations should be monitored and maintained as appropriate (60 to 100%) depending upon the severity of the bleed.

    Intravenous dosage (Wilate)
    Adults, Adolescents, Infants, and Children

    40 to 60 International Units vWF:RCo/kg/dose IV loading dose then 20 to 40 International Units vWF:RCo/kg/dose IV every 12 to 24 hours to keep the nadir concentration of vWF:RCo more than 50%. Therapy may need to be continued for 5 to 7 days.

    For surgical bleeding prophylaxis during major or minor procedures in patients with vWD in whom desmopressin is either ineffective or contraindicated.
    NOTE: Alphanate and Humate-P have been designated by the FDA as orphan drugs for this indication.
    Intravenous dosage (Alphanate)

    NOTE: Alphanate is not indicated for patients with severe (type 3) vWD undergoing major surgery.

    Adults

    Prior to the procedure, give 60 International Units vWF:RCo/kg IV; during clinical trials, this initial infusion was administered 60 minutes prior to the procedure. Subsequent maintenance infusions of 40 to 60 International Units vWF:RCo/kg/dose IV can be administered every 8 to 12 hours as clinically indicated for 1 to 3 days for minor procedures or 3 to 7 days for major procedures. The FVIII:C target peak plasma concentrations are 40 to 50 International Units/dL for minor surgeries and 100 International Units/dL for major procedures. The VWF:RCo and FVIII:C target trough plasma concentration is more than 50 International Units/dL; do not to exceed 150 International Units/dL. Continue treatment until healing is complete. The amount of vWF:RCo and Factor VIII contained in each vial of Alphanate is indicated on the vial's label. The ratio of vWF:RCo to Factor VIII varies by lot; re-evaluate the dosage whenever lot selection is changed.

    Infants, Children, and Adolescents

    Prior to the procedure, give 75 International Units vWF:RCo/kg IV; during clinical trials, this initial infusion was administered 60 minutes prior to the procedure. Subsequent infusions of 50 to 75 International Units vWF:RCo/kg/dose IV can be administered every 8 to 12 hours as clinically indicated for 1 to 3 days for minor procedures or 3 to 7 days for major procedures. The FVIII:C target peak plasma concentrations are 40 to 50 International Units/dL for minor surgeries and 100 International Units/dL for major procedures. The VWF:RCo and FVIII:C target trough plasma concentration is more than 50 International Units/dL; do not to exceed 150 International Units/dL. Continue treatment until healing is complete. The amount of vWF:RCo and Factor VIII contained in each vial of Alphanate is indicated on the vial's label. The ratio of vWF:RCo to Factor VIII varies by lot; re-evaluate the dosage whenever lot selection is changed.

    Intravenous dosage (Humate-P)
    Adults, Adolescents, Children, and Infants

    For emergency surgery, give a loading dose of 50 to 60 International Units/kg IV, and monitor the patient's trough coagulation factor concentrations. For all planned surgeries, calculate a loading dose to give 1 to 2 hours before surgery using the patient's individual in vivo recovery (IVR). To determine the IVR prior to procedure, if possible, measure the baseline plasma VWF:RCo; infuse 60 International Units VWF:RCo/kg IV at time 0, and measure plasma VWF:RCo at time 30 minutes. The IVR is calculated by using the formula: IVR = (Plasma VWF:RCo30 min - Plasma VWF:RCobaseline) / 60 International Units kg. If the IVR is unavailable, assume an IVR of 2 International Units/dL per International Units/kg. The loading dose is calculated using the formula: Loading dose = [(Target VWF:RCo - Baseline VWF:RCo) x Weight] / IVR. For minor surgery: The VWF:RCo target peak plasma concentration is 50 to 60 International Units/dL, and the FVIII:C target peak plasma concentration is 40 to 50 International Units/dL. After achievement of the FVIII:C target concentration, the initial maintenance dose is half of the loading dose. The VWF:RCo target trough plasma concentration is 30 International Units/dL or more for the first 3 days after surgery, and the FVIII:C target trough plasma concentration after day 3 is more than 30 International Units/dL. The minimum treatment duration is 48 hours. For major surgery: The VWF:RCo target peak plasma concentration is 100 International Units/dL and the FVIII:C target peak plasma concentration is 80 to 100 International Units/dL. After achievement of the FVIII:C target concentration, the initial maintenance dose is half of the loading dose. The VWF:RCo and FVIII:C target trough plasma concentrations are greater than 50 International Units/dL for the first 3 days after surgery and greater than 30 International Units/dL after day 3. The minimum treatment duration is 72 hours. For oral surgery: For removal of less than 3 non-molar teeth with no bony involvement, the minimum treatment duration is 8 to 12 hours with at least 1 maintenance dose after surgery based on individual pharmacokinetic values. Removal of more than 1 impacted wisdom tooth is considered major surgery, especially in patients with type 2A or type 3 vWD. Removal of more than 2 teeth is considered major surgery in all patients. Maintenance dose: Frequency is usually every 8 to 12 hours and is determined based on individual pharmacokinetic-derived half-lives. If pharmacokinetic data are unavailable, give Humate-P every 8 hours; monitor trough coagulation factor concentrations to determine any needed adjustments. Monitor trough VWF:RCo and FVIII:C concentrations at least once daily. Consider administration interval and/or dose adjustment for insufficient hemostatic levels or trough concentrations that are outside of the recommended range. Because the ratio of VWF:RCo to FVIII:C activity in Humate-P is 2.4 to 1, any additional dosing will increase VWF:RCo proportionally more than FVIII:C. Assuming an incremental IVR of 2 International Units VWF:RCo/dL per International Units/kg infused, additional dosing to increase FVIII:C in plasma will also increase plasma VWF:RCo by approximately 5 International Units/dL for each International Units/kg of FVIII administered. Do not exceed a trough concentration of 100 International Units/dL for either coagulation factor.

    Intravenous dosage (Wilate)
    Adults, Adolescents, Children, and Infants

    Calculate a loading dose to give within 3 hours before surgery using the patient's individual in vivo recovery (IVR). To determine the IVR prior to procedure, if possible, measure the baseline plasma VWF:RCo; infuse 60 International Units VWF:RCo/kg IV at time 0, and measure plasma VWF:RCo at time 30 minutes. The IVR is calculated by using the formula: IVR = (Plasma VWF:RCo30 min - Plasma VWF:RCobaseline) / 60 International Units kg. If the actual IVR exceeds 2.5, use 2.5 to calculate the loading dose to avoid under dosing. If the IVR is unavailable, assume an IVR of 2 International Units/dL per International Units/kg. The loading dose is calculated using the formula: Loading dose = [(Target VWF:RCo - Baseline VWF:RCo) x Weight] / IVR. Alternately, the following regimens by surgery type provide a dosing range that is expected to provide the desired peak VWF:RCo concentrations. For minor surgery (including tooth extractions): 30 to 60 International Units/kg IV loading dose given within 3 hours before surgery followed by a maintenance dose of 15 to 30 International Units/kg, or one-half the loading dose, every 12 to 24 hours until wound healing is achieved, up to 3 days. The target VWF:RCo peak plasma concentration is 50% of normal with a trough concentration of more than 30% of normal during maintenance doses. For major surgery: 40 to 60 International Units/kg IV loading dose given within 3 hours before surgery followed by a maintenance dose of 20 to 40 International Units/kg, or one-half the loading dose, every 12 to 24 hours until wound healing is achieved, up to at least 6 days. At least 2 doses should be administered within the first 24 hours after surgery. The target VWF:RCo peak plasma concentration is 100% of normal with a trough concentration of more than 50% of normal during maintenance doses. If possible, measure appropriate laboratory tests daily after surgery to ensure adequate VWF:RCo and factor VIII activity concentrations are maintained. To decrease the risk of perioperative thrombosis, factor VIII activity concentrations should not exceed 250% of normal.

    Intravenous dosage (Humate-P general dosing)
    Adults, Adolescents, Children, and Infants

    In general, 40 to 80 International Units vWF:RCo/kg/dose (17 to 33 International Units/kg Humate-P) IV are given every 8 to 12 hours. Doses are repeated as needed based on appropriate clinical and laboratory parameters. Expected levels of vWF:RCo are based on expected in vivo recovery of 2 International Units/dL rise per International Units/kg vWF:RCo administered. The administration of 1 International Units/kg of Factor VIII can be expected to lead to a rise in circulating vWF:RCo of approximately 5 International Units/dL.

    MAXIMUM DOSAGE

    Specific maximum dosage information is not available. Individualize dosage based on the location and severity of the bleed or type of procedure, the clinical status of the patient, the factor VIII activity concentration, and the presence of FVIII inhibitors.

    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

    For storage information, see the specific information within the How Supplied section.

    Injectable Administration
    Intravenous Administration

    Administer under the direct supervision of a physician experienced in the treatment of hemophilia.
    Use only plastic syringes to prepare and administer antihemophilic factor.
    Monitor patients for allergic and infusion-related reactions. Stop infusions for severe reactions. For less severe infusion-related reactions, reduce the rate of administration or temporarily stop the injection to allow symptoms to resolve.
    Coagulation parameters do not necessarily correlate with or predict the effectiveness of treatment. These parameters should be used to adjust treatment schedules, if necessary.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
     
    Reconstitution of human plasma-derived or recombinant antihemophilic factor products
    Consult individual prescribing information for each product as reconstitution procedures and stability information may differ.
    Allow vials to reach room temperature prior to reconstitution. Do not use artificial methods of warming.
    Do not refrigerate after reconstitution.
     
    Direct IV injection or infusion
    May infuse using a controlled infusion device.
    Determine pulse rate before and during administration. If a significant increase in pulse rate occurs, slow or halt the infusion and allow pulse to return to baseline.
    Advate, Adynovate: Administer IV as bolus infusion over a period of 5 minutes or less (maximum infusion rate 10 mL/minute).
    Afstyla, Alphanate, Hemofil M, or Monarc-M: Administer IV at a rate not to exceed 10 mL/minute.
    Humate-P: Administer IV at a rate no faster than 4 mL/minute.
    Helixate FS, Kogenate FS: Administer IV over 1 to 15 minutes; adapt the rate to the individual patient's response.
    Koate: Administer IV at a rate not to exceed 10 mL/minute; adapt the rate to the individual patient's response.
    Koate-DVI: Administer IV over 5 to 10 minutes.
    Kovaltry: Administer IV over 1 to 15 minutes; adapt the rate to the individual's response.
    Monoclate-P: Administer IV at a rate of approximately 2 mL/minute.
    Novoeight: Administer IV over 2 to 5 minutes.
    Nuwiq: Administer IV at a rate no faster than 4 mL/minute; determine rate by the patient's comfort level.
    Recombinate: Administer IV at a rate up to 5 mL/minute; determine rate by the patient's comfort level.
    ReFacto, Xyntha: Administer IV over several minutes; determine rate by the patient's comfort level.
    Wilate: Administer IV at a rate of 2 to 4 mL/minute.
     
    Continuous intravenous infusion:
    NOTE: Antihemophilic Factor, AHF, Factor VIII is not FDA-approved for continuous intravenous infusion.
    Infuse using a controlled infusion device.
    The following factor VIII agents have been shown to maintain activity more than 80% above baseline in a polypropylene container at 20 to 23 degrees C for at least 24 hours: Hemofil M, Humate-P, Monoclate-P, and Recombinate.
    Many of the high-purity or recombinant factor formulations have demonstrated stability when administered via continuous infusion for at least 1 to 3 days. The factors should be reconstituted as directed by the manufacturer and not further diluted as they may not be stable if further diluted. One study indicates that when FVIII (Kogenate) was infused through polyethylene tubing, a decrease in activity was apparent for the first 5 mL most likely due to adsorption of the concentrate to the tubing. In contrast, a decrease in activity was not apparent when infused through polyvinyl chloride tubing.

    STORAGE

    Advate:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Do not refrigerate reconstituted product
    - May be stored at temperatures up to 86 degrees F for up to 6 months
    - Product stored at controlled room temperature should not be returned to a refrigerator
    - Store unreconstituted product in refrigerator (36 to 46 degrees F)
    Adynovate :
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Do not freeze
    - Do not refrigerate reconstituted product
    - May be stored at temperatures up to 86 degrees F for up to 3 months
    - Protect from light
    - Reconstituted product should be used within 3 hours
    - Refrigerate (between 36 and 46 degrees F)
    - See package insert for detailed storage information
    - Store in original container
    AFSTYLA:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Do not freeze
    - May store unreconstituted product at room temperature (up to 77 degrees F) for up to 3 months
    - Product stored at controlled room temperature should not be returned to a refrigerator
    - Protect from light
    - Reconstituted product may be stored in refrigerator (36 to 46 degrees F) or at room temperature (up to 77 degrees F)
    - Reconstituted product must be used within 4 hours
    - Refrigerate (between 36 and 46 degrees F)
    - Store in original container
    Alphanate:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Do not freeze
    - Reconstituted product should be used within 3 hours
    - Store below 77 degrees F
    Helixate FS:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Protect from light
    - Reconstituted product should be used within 3 hours
    - Store between 36 to 46 degrees F
    - Store in carton until time of use
    Hemofil M:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Do not freeze
    - Store in refrigerator (36 to 46 degrees F) or at room temperature, not to exceed 86 degrees F
    Humate-P:
    - Do not freeze
    - Reconstituted product should be used within 3 hours
    - Store at room temperature (up to 77 degrees F)
    Koate:
    - Discard unused portion. Do not store for later use.
    - Do not freeze
    - May be stored at room temperature not exceeding 77 degrees F for up to 6 months
    - Protect from light
    - Reconstituted product should be used within 3 hours
    - Store between 36 to 46 degrees F
    - Store in original container
    Koate-DVI:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Refrigerate (between 36 and 46 degrees F)
    - Unreconstituted product may be stored at room temperature not exceeding 77 degrees F for up to 6 months
    Kogenate FS:
    - Do not freeze
    - May be stored at a temperature not exceeding 77 degrees F after first use
    - Product stored at controlled room temperature should not be returned to a refrigerator
    - Protect from light
    - Reconstituted product should be used within 3 hours
    - Refrigerate (between 36 and 46 degrees F)
    - Store in carton until time of use
    Kovaltry :
    - Avoid prolonged exposure to light
    - Do not freeze
    - Store in carton until time of use
    - Store unreconstituted product in refrigerator (36 to 46 degrees F)
    - Unreconstituted product may be stored at temperatures up to 77 degrees F for a single period of up to 12 months
    Monarc-M:
    - Protect from freezing
    - Store in refrigerator (36 to 46 degrees F) or at room temperature, not to exceed 86 degrees F
    Monoclate-P:
    - May be stored at room temperature not exceeding 77 degrees F for up to 6 months
    - Protect from freezing
    - Reconstituted product should be used within 3 hours
    - Refrigerate (between 36 and 46 degrees F)
    Novoeight:
    - Do not freeze
    - May be stored at room temperature not exceeding 86 degrees F for up to 12 months
    - Product is stable until the expiration date on the label if refrigerated (36 to 46 degrees F)
    - Product stored at controlled room temperature should not be returned to a refrigerator
    - Protect from light
    - Reconstituted product must be used within 4 hours
    - See package insert for detailed storage information
    - Store in original container
    Nuwiq:
    - Discard unused portion. Do not store for later use.
    - Do not freeze
    - May be stored at room temperature not exceeding 77 degrees F for up to 3 months
    - Product stored at controlled room temperature should not be returned to a refrigerator
    - Protect from light
    - Reconstituted product should be used within 3 hours
    - Store in original container
    - Store unreconstituted product in refrigerator (36 to 46 degrees F)
    Recombinate:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Do not refrigerate reconstituted product
    - Protect from light
    - Reconstituted product should be used within 3 hours
    - Store in original package until time of use
    - Store in refrigerator (36 to 46 degrees F) or at room temperature, not to exceed 86 degrees F
    ReFacto:
    - May be stored at room temperature not exceeding 77 degrees F for up to 3 months
    - Protect from freezing
    - Protect from light
    - Store unreconstituted product between 36 and 77 degrees F
    Wilate vonWillebrand:
    - Do not freeze
    - May be stored at room temperature not exceeding 77 degrees F for up to 6 months
    - Product stored at controlled room temperature should not be returned to a refrigerator
    - Protect from light
    - Store in original container
    - Store product in refrigerator (36 to 46 degrees F) for up to 36 months from date of manufacture
    XYNTHA:
    - Do not freeze
    - May be stored at room temperature not exceeding 77 degrees F for up to 3 months
    - Protect from light
    - Store product in refrigerator (36 to 46 degrees F) for up to 36 months from date of manufacture
    XYNTHA Solofuse:
    - Do not freeze
    - May store unreconstituted product at room temperature (up to 77 degrees F) for up to 3 months
    - Protect from light
    - Refrigerate (between 36 and 46 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    In hemophilic patients, the development of inhibitors (i.e., antibody formation) to factor VIII can occur. These antibodies are reported to be present in 5—15% of patients with severe hemophilia and a few with mild hemophilia. Patients with inhibitors present may or may not respond to treatment with AHF. These patients can have bleeding problems that are difficult to control and require careful monitoring and, possibly, other treatments, especially when surgery is required. In addition, patients with type 3, severe von Willebrand Disease may develop alloantibodies to von Willebrand factor after replacement therapy. The risk of developing these antibodies is unknown.

    Pregnancy

    There are no data in women or animals during pregnancy, and its ability to cause fetal harm or affect the reproductive capacity is unknown. Antihemophilic factor (AHF) should be used during pregnancy only if clearly needed.

    Breast-feeding

    There are no data describing the excretion of antihemophilic factor (AHF) in breast milk, the effect on the breastfed infant, or the effect on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for AHF and any potential adverse effects on the breastfed infant from AHF or the mother's underlying condition.

    Thromboembolic disease

    Thrombosis and thromboembolism have been reported in patients with von Willebrand Disease receiving antihemophilic factor/von Willebrand factor complex replacement therapy, especially in patients with known risk factors for thromboembolic disease (e.g., pregnancy, certain thrombophilias). Early reports indicate that the incidence may be higher in females. High concentrations of endogenous Factor VIII have also been associated with thrombosis, although a causal relationship has not yet been established. Caution is advised when administering antihemophilic factor to patients with risk factors for thrombosis and/or thromboembolic disease; antithrombotic measures should be considered.

    Hepatitis, infection, viral infection

    As with other products derived from or purified with human blood components, the possibility of contamination with hepatitis and other viral or bacterial infections exists in patients receiving plasma-derived antihemophilic factor products (i.e., Alphanate, Hemofil M, Humate-P, Koate-HP, Koate-DVI, Monarc-M, Monoclate-P, and Wilate). Screening plasma donors for prior exposure to certain viruses, testing for the presence of viruses, and inactivating and/or reducing viruses has reduced the risk of transmission of infectious agents. The manufacturing processes are designed to reduce the risk of transmitting viral infection; however, none of the processes are completely effective. There is also the possibility that unknown infectious agents may be present in these products. It is recommended that all patients with hemophilia receive vaccination against hepatitis A and B at birth or at diagnosis of hemophilia.

    Anemia

    Certain brands of antihemophilic factor, specifically Alphanate, Humate-P, Koate-HP, contain small amounts of isoagglutinins for blood groups A and B. Caution and frequent monitoring (hematocrit and Coombs' test) is advised when giving large or frequently repeated doses to patients with blood groups A, B, and AB due to the possibility of developing anemia and intravascular hemolysis.

    Bovine protein hypersensitivity, hamster protein hypersensitivity, latex hypersensitivity, mannitol hypersensitivity, murine protein hypersensitivity, polysorbate 80 hypersensitivity

    Antihemophilic factor, AHF, factor VIII is contraindicated in patients who have had life-threatening hypersensitivity reactions to any constituents of the product. Monoclonal antibody-purified and recombinant antihemophilic factor products contain varying amounts of animal protein and should be used with caution in patients with bovine protein hypersensitivity, hamster protein hypersensitivity, and murine protein hypersensitivity. Hemofil M and Monoclate-P contain trace amounts of murine proteins from the purification process. Recombinate contains trace amounts of bovine, hamster, and mouse proteins. Helixate FS, Kogenate FS, ReFacto, Advate, Adynovate, and Kovaltry contain trace amounts of hamster and mouse proteins. Afstyla, Novoeight, and Xyntha contain trace amounts of hamster proteins. Advate, Adynovate, and Monoclate-P contain mannitol and are contraindicated in patients who have a mannitol hypersensitivity. Advate, Adynovate, Afstyla, Helixate FS, Koate-DVI, Kogenate FS, Kovaltry, Novoeight, Recombinate, and Xyntha contain polysorbate 80 and are contraindicated in patients with a polysorbate 80 hypersensitivity. Use Recombinate with caution in patients with a latex hypersensitivity; certain components used in the packaging contain natural rubber latex.

    Porcine protein hypersensitivity

    Hyate:C should be used cautiously in patients with porcine protein hypersensitivity. Patients with porcine AHF titers > 20 Bethesda units are unlikely to benefit from treatment with Hyate:C.

    Human immunodeficiency virus (HIV) infection

    Hemophilia A patients with human immunodeficiency virus (HIV) infection or who are HIV seropositive may benefit from treatment with ultra-pure, antihemophilic factor (AHF) products (i.e., monoclonal antibody purified or recombinant products). Studies have shown improved immune function in hemophilia A patients receiving high purity factor VIII products.

    Cardiac disease

    Once clotting has been normalized by treatment with antihemophilic factor, AHF, factor VIII, hemophilic patients with cardiovascular risk factors or cardiac disease may be at the same risk to develop cardiovascular events as non-hemophilic patients.

    ADVERSE REACTIONS

    Severe

    anaphylactic shock / Rapid / 0-1.0
    anaphylactoid reactions / Rapid / 0-1.0
    angioedema / Rapid / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    pulmonary embolism / Delayed / Incidence not known
    thromboembolism / Delayed / Incidence not known
    thrombosis / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    bradycardia / Rapid / Incidence not known
    cyanosis / Early / Incidence not known
    bronchospasm / Rapid / Incidence not known

    Moderate

    antibody formation / Delayed / 0.5-30.0
    dyspnea / Early / 2.8-2.8
    orthostatic hypotension / Delayed / 2.6-2.6
    peripheral vasodilation / Rapid / 2.3-2.3
    phlebitis / Rapid / 1.5-1.5
    elevated hepatic enzymes / Delayed / 1.4-1.4
    peripheral edema / Delayed / 1.4-1.4
    hyperbilirubinemia / Delayed / 0.5-0.5
    angina / Early / 0.5-0.5
    hypotension / Rapid / 0.5-0.5
    sinus tachycardia / Rapid / 0.5-0.5
    erythema / Early / 0.4-0.4
    edema / Delayed / Incidence not known
    hemolysis / Early / Incidence not known
    bleeding / Early / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    palpitations / Early / Incidence not known
    wheezing / Rapid / Incidence not known

    Mild

    headache / Early / 0.8-26.0
    arthralgia / Delayed / 12.0-25.0
    cough / Delayed / 0.5-19.0
    pharyngitis / Delayed / 17.0-17.0
    nausea / Early / 0.5-13.0
    vomiting / Early / 1.5-12.0
    infection / Delayed / 0.5-9.0
    diarrhea / Early / 5.0-8.0
    nasal congestion / Early / 8.0-8.0
    asthenia / Delayed / 1.4-7.0
    injection site reaction / Rapid / 0.4-6.6
    rhinorrhea / Early / 5.0-5.0
    dizziness / Early / 0.5-2.2
    dysgeusia / Early / 0.8-1.4
    flushing / Rapid / 1.0-1.0
    drowsiness / Early / 0.9-0.9
    anorexia / Delayed / 0.9-0.9
    hyperhidrosis / Delayed / 0.5-0.5
    tremor / Early / 0.5-0.5
    abdominal pain / Early / 0.5-0.5
    myalgia / Early / 0.5-0.5
    pallor / Early / 0.5-0.5
    chills / Rapid / 0.4
    urticaria / Rapid / 0.5
    pruritus / Rapid / 0.4
    fever / Early / 0.4
    rash (unspecified) / Early / 0.4
    paresthesias / Delayed / 0.4
    fatigue / Early / 0.5
    epistaxis / Delayed / 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 antihemophilic factor, AHF, factor VIII should be avoided due to the potential for thrombosis.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no data in women or animals during pregnancy, and its ability to cause fetal harm or affect the reproductive capacity is unknown. Antihemophilic factor (AHF) should be used during pregnancy only if clearly needed.

    There are no data describing the excretion of antihemophilic factor (AHF) in breast milk, the effect on the breastfed infant, or the effect on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for AHF and any potential adverse effects on the breastfed infant from AHF or the mother's underlying condition.

    MECHANISM OF ACTION

    Factor VIII (FVIII) acts in the coagulation cascade to accelerate the cleavage of factor X by activated factor IX. FVIII dramatically increases the maximal velocity of the reaction. Low concentrations of FVIII (0.2 ng/mL of plasma) are required for normal hemostasis. A severe decrease (> 80%) or lack of the factor lead to the bleeding disorder known as hemophilia A or classical hemophilia. FVIII circulates in a noncovalent complex with von Willebrand factor (vWF). The complex with vWF increases the synthesis of FVIII, protects FVIII from proteolysis, and concentrates FVIII at the site of active bleeding. FVIII can not become part of the "tenase" complex (the calcium-dependent complex of activated FVIII (FVIIIa), factor IXa and phospholipid) until it is released from vWF since vWF inhibits the binding of FVIII to phospholipid. The release of FVIII from vWF requires cleavage of the FVIII light chain by thrombin or factor Xa. This results in activation of FVIII and binding of FVIIIa to phospholipid surfaces of damaged cells and activated platelets. FVIIIa is unstable and rapidly loses its activity. FVIIIa undergoes subunit disassociation and is inactivated via proteolytic cleavage by activated protein C.
     
    The increase in FVIII:C activity produced by AHF differs by product. One unit of recombinant AHF per kg body weight increases FVIII:C activity approximately 2 units/dL. Each unit per kg body weight porcine AHF increases FVIII:C approximately 1.5 units/dL. One unit per kg body weight of Humate-P(R) increases the FVIII:C activity level 2 units/dL and increases vWF:RCof activity 3.5—4 units/dL. The increase in FVIII:C activity following one unit per kg body weight of other plasma derived AHF products is 2—2.5 units/dL.

    PHARMACOKINETICS

    Antihemophilic factor, AHF, factor VIII is administered intravenously. Factor VIII products are labeled in terms of AHF potency (FVIII:C activity) as International Units. Antihemophilic factor/von Willebrand factor complex products also include the activity of von Willebrand factor expressed as von Willebrand factor:Ristocetin Cofactor (vWF:RCo) and labeled as International Units. These units are referenced to a World Health Organization international standard where 1 International Unit indicates the amount of factor VIII or vWF:RCo present in 1 mL of fresh-pooled plasma.
     
    The distribution of AHF is limited to the plasma. The half-life of plasma-derived AHF and recombinant AHF are similar and is approximately 15 hours (range 8 to 17.5 hours). The mean in vivo recovery (IVR) of AHF products is 1.9 to 2.74 International Units/dL per International Units/kg and indicates the increase in factor concentration achieved after infusion of a given amount of factor product. Porcine AHF (i.e., Hyate:C) has a half-life of approximately 7 hours (range 2 to 9 hours). The half-life of all AHF products is reduced in patients with factor VIII inhibitors.
     
    The half-life of vWF:RCo in patients receiving antihemophilic factor/von Willebrand factor complex is 7.67 to 15.8 hours. The in vivo recovery (IVR) of vWF:RCo is 1.9 to 3.3 International Units/dL per International Units/kg.

    Intravenous Route

    After IV administration, AHF is quickly cleared from the plasma. The peak effect of activity occurs 1 to 2 hours after IV administration.