Antihemophilic Factor, AHF, Factor VIII

Indications/Dosage

Labeled

bleeding prophylaxis
hemophilia A
hemorrhage
surgical bleeding
von Willebrand's disease

Off-Label

† Off-label indication

For the on-demand treatment and control of hemorrhage in patients with hemophilia A (classical hemophilia)

NOTE: Kogenate FS and Xyntha have been designated by the FDA as orphan drugs for this indication.

NOTE: Factor VIII concentration may be expressed as % or International Units/dL.

for minor bleeding including early muscle bleed, early hemarthrosis, and oral bleeds

Intravenous dosage (Advate)

Adults

10 to 20 International Units/kg/dose to achieve a target factor VIII activity concentration of 20% to 40% of normal; repeat the dose every 12 to 24 hours until bleeding is resolved (approximately 1 to 3 days). Alternately, use the following formula: Dose (International Units) = Body weight (kg) x Desired Factor VIII Rise (International Units/dL or % of normal) x 0.5 (International Unit/kg per International Unit/dL). Adjust dose based on clinical response.[56320]

Children and Adolescents 6 to 17 years

Infants and Children younger than 6 years

10 to 20 International Units/kg/dose to achieve a target factor VIII activity concentration of 20% to 40% of normal; repeat the dose every 8 to 24 hours until bleeding is resolved (approximately 1 to 3 days). Alternately, use the following formula: Dose (International Units) = Body weight (kg) x Desired Factor VIII Rise (International Units/dL or % of normal) x 0.5 (International Unit/kg per International Unit/dL). Adjust dose based on clinical response.[56320]

Intravenous dosage (Adynovate)

Adults

10 to 20 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 20% to 40% of normal; repeat the dose every 12 to 24 hours until bleeding is resolved.[60296]

Children and Adolescents

10 to 20 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 20% to 40% of normal; repeat the dose every 12 to 24 hours until bleeding is resolved.[60296]

Intravenous dosage (Afstyla)

Adults

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.[60830]

Infants, Children, and Adolescents

Intravenous dosage (Alphanate)

Adults

10 to 15 International Units/kg/dose IV to achieve a peak postinfusion factor VIII activity concentration of 20% to 30% of normal; most minor bleeds can be treated with 1 dose.

Infants, Children, and Adolescents

10 to 15 International Units/kg/dose IV to achieve a peak postinfusion factor VIII activity concentration of 20% to 30% of normal; most minor bleeds can be treated with 1 dose.

Intravenous dosage (Esperoct)

Adults

40 International Units/kg/dose IV; 1 dose should be sufficient. Alternately, to achieve a specific target factor VIII activity concentration, use the following formula: Dose (International Units) = Body Weight (kg) x Desired Factor VIII Increase (International Units/dL or % of normal) x 0.5. Base dose on individual clinical response.[63978]

Children and Adolescents 12 to 17 years

Children 1 to 11 years

65 International Units/kg/dose IV; 1 dose should be sufficient. Alternately, to achieve a specific target factor VIII activity concentration, use the following formula: Dose (International Units) = Body Weight (kg) x Desired Factor VIII Increase (International Units/dL or % of normal) x 0.5. Base dose on individual clinical response.[63978]

Intravenous dosage (Helixate FS, Kogenate FS)

Adults

10 to 20 International Units/kg/dose IV to achieve a peak postinfusion factor VIII activity concentration of 20% to 40% of normal; repeat the dose if bleeding or pain continues.

Infants, Children, and Adolescents

10 to 20 International Units/kg/dose IV to achieve a peak postinfusion factor VIII activity concentration of 20% to 40% of normal; repeat the dose if bleeding or pain continues.

Intravenous dosage (Hemofil M)

Adults

Dose IV to achieve a target factor VIII activity concentration of 20% to 40% of normal; repeat the dose every 12 to 24 hours for 1 to 3 days until bleeding is resolved and healing is achieved. Use the following formula: Dose (International Units) = Body weight (kg) x Desired Factor VIII Rise (International Units/dL or % of normal) x 0.5 (International Unit/kg per International Unit/dL). Adjust dose based on clinical response.[56332]

Infants, Children, and Adolescents

Intravenous dosage (Humate-P)

Adults

15 International Units/kg/dose IV to achieve a peak postinfusion factor VIII activity concentration of 30% of normal; most minor bleeds can be treated with 1 dose. If needed, half of the dose may be given 1 to 2 times daily for 1 to 2 days.

Infants, Children, and Adolescents

Intravenous dosage (Jivi)

Adults

10 to 20 International Units/kg/dose [Max: 6,000 International Units/dose (round to vial size)] IV to achieve a target factor VIII activity concentration of 20% to 40% of normal; repeat the dose every 24 to 48 hours until bleeding is resolved.[63486]

Children and Adolescents 12 to 17 years

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.[61730]

Children and Adolescents

Intravenous dosage (Koate-DVI)

Adults

10 International Units/kg/dose IV to achieve a peak postinfusion factor VIII activity concentration of 20% of normal; repeat the dose if there is evidence of continued bleeding.

Infants, Children, and Adolescents

10 International Units/kg/dose IV to achieve a peak postinfusion factor VIII activity concentration of 20% of normal; repeat the dose if there is evidence of continued bleeding.

Intravenous dosage (Kovaltry)

Adults

10 to 20 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 20% to 40% of normal; repeat the dose every 12 to 24 hours for at least 1 day, until bleeding episode as indicated by pain is resolved, or healing is achieved.[60650]

Infants, Children, and Adolescents

Intravenous dosage (Monoclate-P)

Adults

15 International Units/kg/dose IV to achieve a peak postinfusion factor VIII activity concentration of 30% of normal; most minor bleeds can be treated with 1 dose.

Infants, Children, and Adolescents

15 International Units/kg/dose IV to achieve a peak postinfusion factor VIII activity concentration of 30% of normal; most minor bleeds can be treated with 1 dose.

Intravenous dosage (Novoeight)

Adults

10 to 20 International Units/kg/dose IV to achieve a peak postinfusion factor VIII activity concentration of 20% to 40% of normal; repeat the dose every 12 to 24 hours for at least 1 day and until bleeding is resolved.[56302]

Infants, Children, and Adolescents

Intravenous dosage (Nuwiq)

Adults

Children and Adolescents 2 to 17 years

Intravenous dosage (Recombinate)

Adults

Infants, Children, and Adolescents

Intravenous dosage (Wilate)

Adults

30 to 40 International Units/kg IV every 12 to 24 hours for at least 1 day until bleeding has resolved. Alternately, use the following formula: Dose (International Units) = Body weight (kg) x Desired Factor VIII Rise (International Units/dL or % of normal) x 0.5 (International Unit/kg per International Unit/dL). Adjust dose based on clinical response.[56305]

Adolescents

Intravenous dosage (Xyntha)

Adults

10 to 20 International Units/kg/dose IV to achieve a peak postinfusion factor VIII activity concentration of 20% to 40% of normal; repeat the dose every 12 to 24 hours until resolved and for at least 1 day depending on the severity of the bleeding episode.[49402]

Infants, Children, and Adolescents

for moderate bleeding including advanced muscle bleed, extensive hemarthrosis, hematoma, and mild head trauma

Intravenous dosage (Advate)

Adults

15 to 30 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 30% to 60% of normal; repeat the dose every 12 to 24 hours until bleeding is resolved (approximately 3 days or more). Alternately, use the following formula to estimate the dose: Dose (International Units) = Body weight (kg) x Desired Factor VIII Rise (International Units/dL or % of normal) x 0.5 (International Unit/kg per International Unit/dL). Adjust dose based on clinical response.[56320]

Children and Adolescents 6 to 17 years

Infants and Children younger than 6 years

15 to 30 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 30% to 60% of normal; repeat the dose every 8 to 24 hours until bleeding is resolved (approximately 3 days or more). Alternately, use the following formula to estimate the dose: Dose (International Units) = Body weight (kg) x Desired Factor VIII Rise (International Units/dL or % of normal) x 0.5 (International Unit/kg per International Unit/dL). Adjust dose based on clinical response.[56320]

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 the dose every 12 to 24 hours until bleeding is resolved.[60296]

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 the dose every 12 to 24 hours until bleeding is resolved.[60296]

Intravenous dosage (Afstyla)

Adults

15 to 30 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 30% to 60% of normal; repeat the dose every 12 to 24 hours for 3 to 4 days or more until pain and acute disability resolved.[60830]

Infants, Children, and Adolescents

Intravenous dosage (Alphanate)

Adults

10 to 15 International Units/kg/dose IV to achieve a peak postinfusion factor VIII activity concentration of 20% to 30% of normal; repeat the dose if bleeding recurs.

Infants, Children, and Adolescents

10 to 15 International Units/kg/dose IV to achieve a peak postinfusion factor VIII activity concentration of 20% to 30% of normal; repeat the dose if bleeding recurs.

Intravenous dosage (Esperoct)

Adults

40 International Units/kg/dose IV; may give an additional dose after 24 hours. Alternately, to achieve a specific target factor VIII activity concentration, use the following formula: Dose (International Units) = Body Weight (kg) x Desired Factor VIII Increase (International Units/dL or % of normal) x 0.5. Base dose on individual clinical response.[63978]

Children and Adolescents 12 to 17 years

Children 1 to 11 years

65 International Units/kg/dose IV; may give an additional dose after 24 hours. Alternately, to achieve a specific target factor VIII activity concentration, use the following formula: Dose (International Units) = Body Weight (kg) x Desired Factor VIII Increase (International Units/dL or % of normal) x 0.5. Base dose on individual clinical response.[63978]

Intravenous dosage (Helixate FS, Kogenate FS)

Adults

15 to 30 International Units/kg/dose IV to achieve a peak postinfusion factor VIII activity concentration of 30% to 60% of normal; repeat the dose after 12 to 24 hours, if needed.

Infants, Children, and Adolescents

15 to 30 International Units/kg/dose IV to achieve a peak postinfusion factor VIII activity concentration of 30% to 60% of normal; repeat the dose after 12 to 24 hours, if needed.

Intravenous dosage (Hemofil M)

Adults

Dose IV to achieve a target factor VIII activity concentration of 30% to 60% of normal; repeat the dose every 12 to 24 hours for 3 days or more until pain and disability are resolved. Use the following formula: Dose (International Units) = Body weight (kg) x Desired Factor VIII Rise (International Units/dL or % of normal) x 0.5 (International Unit/kg per International Unit/dL). Adjust dose based on clinical response.[56332]

Infants, Children, and Adolescents

Intravenous dosage (Humate-P)

Adults

25 International Units/kg/dose IV to achieve a factor VIII 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 factor VIII activity concentration of about 30% of normal; then continue the same dose 1 to 2 times daily for up to 7 days or until adequate wound healing.

Infants, Children, and Adolescents

Intravenous dosage (Jivi)

Adults

15 to 30 International Units/kg/dose IV [Max: 6,000 International Units/dose (round to vial size)] to achieve a target factor VIII activity concentration of 30% to 60% of normal; repeat the dose every 24 to 48 hours until bleeding episode is resolved.[63486]

Children and Adolescents 12 to 17 years

15 to 30 International Units/kg/dose [Max: 6,000 International Units/dose (round to vial size)] IV to achieve a target factor VIII activity concentration of 30% to 60% of normal; repeat the dose every 24 to 48 hours until bleeding episode is resolved.[63486]

Intravenous dosage (Koate)

Adults

25 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 50% of normal; repeat the dose every 12 hours until healing is achieved, typically 2 to 7 days.[61730]

Children and Adolescents

25 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 50% of normal; repeat the dose every 12 hours until healing is achieved, typically 2 to 7 days.[61730]

Intravenous dosage (Koate-DVI, Monoclate-P)

Adults

15 to 25 International Units/kg/dose IV to achieve a peak postinfusion factor VIII 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.

Infants, Children, and Adolescents

Intravenous dosage (Kovaltry)

Adults

Infants, Children, and Adolescents

Intravenous dosage (Novoeight)

Adults

15 to 30 International Units/kg/dose IV to achieve a peak postinfusion factor VIII activity concentration of 30% to 60% of normal; repeat the dose every 12 to 24 hours for approximately 3 to 4 days or until pain and acute disability are resolved.[56302]

Infants, Children, and Adolescents

Intravenous dosage (Nuwiq)

Adults

15 to 30 International Units/kg/dose IV to achieve a peak postinfusion factor VIII activity concentration of 30% to 60% of normal; repeat the dose every 12 to 24 hours for 3 to 4 days or until bleeding is resolved.[60156]

Children and Adolescents 2 to 17 years

Intravenous dosage (Recombinate)

Adults

Infants, Children, and Adolescents

Intravenous dosage (Wilate)

Adults

30 to 40 International Units/kg IV every 12 to 24 hours for at least 3 to 4 days until bleeding has resolved. Alternately, use the following formula: Dose (International Units) = Body weight (kg) x Desired Factor VIII Rise (International Units/dL or % of normal) x 0.5 (International Unit/kg per International Unit/dL). Adjust dose based on clinical response.[56305]

Adolescents

Intravenous dosage (Xyntha)

Adults

Infants, Children, and Adolescents

for life- or limb-threatening, gastrointestinal, intracranial, intraabdominal, or intrathoracic bleeding; neck, tongue, or pharyngeal hematoma with potential for airway compromise; fractures

Intravenous dosage (Advate)

Adults

30 to 50 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 60% to 100% of normal; repeat the dose every 8 to 24 hours until bleeding is resolved. Alternately, use the following formula: Dose (International Units) = Body weight (kg) x Desired Factor VIII Rise (International Units/dL or % of normal) x 0.5 (International Unit/kg per International Unit/dL). Adjust dose based on clinical response.[56320]

Children and Adolescents 6 to 17 years

Infants and Children younger than 6 years

30 to 50 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 60% to 100% of normal; repeat the dose every 6 to 12 hours until bleeding is resolved. Alternately, use the following formula: Dose (International Units) = Body weight (kg) x Desired Factor VIII Rise (International Units/dL or % of normal) x 0.5 (International Unit/kg per International Unit/dL). Adjust dose based on clinical response.[56320]

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 the dose every 8 to 24 hours until bleeding is resolved.[60296]

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 the dose every 8 to 24 hours until bleeding is resolved.[60296]

Intravenous dosage (Afstyla)

Adults

30 to 50 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 60% to 100% of normal; repeat the dose every 8 to 24 hours until bleeding episode is resolved.[60830]

Infants, 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 the dose every 8 to 24 hours until bleeding episode is resolved.[60830]

Intravenous dosage (Alphanate)

Adults

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

Infants, Children, and Adolescents

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

Intravenous dosage (Esperoct)

Adults

50 International Units/kg/dose IV; may give additional doses approximately every 24 hours. Alternately, to achieve a specific target factor VIII activity concentration, use the following formula: Dose (International Units) = Body Weight (kg) x Desired Factor VIII Increase (International Units/dL or % of normal) x 0.5. Base dose on individual clinical response.[63978]

Children and Adolescents 12 to 17 years

Children 1 to 11 years

65 International Units/kg/dose IV; may give additional doses approximately every 24 hours. Alternately, to achieve a specific target factor VIII activity concentration, use the following formula: Dose (International Units) = Body Weight (kg) x Desired Factor VIII Increase (International Units/dL or % of normal) x 0.5. Base dose on individual clinical response.[63978]

Intravenous dosage (Helixate FS, Kogenate FS, Koate-DVI, Monoclate-P)

Adults

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

Infants, Children, and Adolescents

Intravenous dosage (Hemofil M)

Adults

Dose IV to achieve a target factor VIII activity concentration of 60% to 100% of normal; repeat the dose every 8 to 24 hours until the threat is resolved. Use the following formula: Dose (International Units) = Body weight (kg) x Desired Factor VIII Rise (International Units/dL or % of normal) x 0.5 (International Unit/kg per International Unit/dL). Adjust dose based on clinical response.[56332]

Infants, Children, and Adolescents

Intravenous dosage (Humate-P)

Adults

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

Infants, Children, and Adolescents

Intravenous dosage (Jivi)

Adults

30 to 50 International Units/kg/dose [Max: 6,000 International Units/dose (round to vial size)] IV to achieve a target factor VIII activity concentration of 60% to 100% of normal; repeat the dose every 8 to 24 hours until bleeding is resolved.[63486]

Children and Adolescents 12 to 17 years

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.[61730]

Children and Adolescents

Intravenous dosage (Kovaltry)

Adults

30 to 50 International Units/kg/dose IV to achieve a target factor VIII activity concentration of 60% to 100% of normal; repeat the dose every 8 to 24 hours until bleeding is resolved.[60650]

Infants, 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 the dose every 8 to 24 hours until bleeding is resolved.[60650]

Intravenous dosage (Novoeight)

Adults

30 to 50 International Units/kg/dose IV to achieve a peak postinfusion factor VIII activity concentration of 60% to 100% of normal; repeat the dose every 8 to 24 hours until bleeding is resolved (approximately 7 to 10 days).[56302]

Infants, Children, and Adolescents

Intravenous dosage (Nuwiq)

Adults

Children and Adolescents 2 to 17 years

Intravenous dosage (Recombinate)

Adults

Infants, Children, and Adolescents

Intravenous dosage (Wilate)

Adults

35 to 50 International Units/kg IV every 12 to 24 hours for at least 3 to 4 days until bleeding has resolved for major bleeding or every 8 to 24 hours until the threat has resolved for life-threatening bleeding. Alternately, use the following formula: Dose (International Units) = Body weight (kg) x Desired Factor VIII Rise (International Units/dL or % of normal) x 0.5 (International Unit/kg per International Unit/dL). Adjust dose based on clinical response.[56305]

Adolescents

Intravenous dosage (Xyntha)

Adults

Infants, Children, and Adolescents

Continuous infusion dosage†

Adults

50 International Units/kg IV loading dose to achieve a peak postinfusion factor VIII activity concentration of 80% to 100% of normal; then 2 International Units/kg/hour continuous IV infusion adjusted based upon the plasma factor VIII activity concentrations has been used. For the first 7 days or until bleeding resolves, the goal is a factor VIII activity concentration of 80% to 100%. Once bleeding resolves, the rate of the infusion may be decreased to maintain factor VIII activity concentrations of 30% to 50% depending upon the clinical status of the patient.[25743] A higher rate of infusion of 4 to 5 International Units/kg/hour has also been suggested.[32317]

Infants, Children, and Adolescents

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

Dosage not established. In general, higher doses than those normally required for a particular bleed episode are needed. Base doses 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 factor VIII activity concentrations is needed. Repeat doses as needed until desired factor VIII activity concentration is reached, then doses continue every 8 to 12 hours to maintain the factor VIII activity in the therapeutic range.

Infants, Children, and Adolescents

For the perioperative management of surgical bleeding in patients with hemophilia A

Intravenous dosage (Advate)

Adults

For minor surgical procedures, including tooth extraction, 30 to 50 International Units/kg/dose IV within 1 hour before surgery to achieve a peak postinfusion factor VIII activity concentration of 60% to 100% of normal; repeat every 12 to 24 hours as necessary until bleeding is resolved. May consider adjunctive therapy for dental procedures. For major surgery, 40 to 60 International Units/kg/dose IV preoperatively to achieve a peak postinfusion factor VIII activity concentration of 100 % of normal (80% to 120% pre- and postoperative); repeat every 8 to 24 hours until healing is achieved and to maintain desired factor VIII activity concentration. Alternately, use the following formula: Dose (International Units) = Body weight (kg) x Desired Factor VIII Rise (International Units/dL or % of normal) x 0.5 (International Unit/kg per International Unit/dL). Adjust dose based on clinical response.[56320]

Children and Adolescents 6 to 17 years

Infants and Children younger than 6 years

For minor surgical procedures, including tooth extraction, 30 to 50 International Units/kg/dose IV within 1 hour before surgery to achieve a peak postinfusion factor VIII activity concentration of 60% to 100% of normal; repeat every 12 to 24 hours as necessary until bleeding is resolved. May consider adjunctive therapy for dental procedures. For major surgery, 40 to 60 International Units/kg/dose IV preoperatively to achieve a peak postinfusion factor VIII activity concentration of 100 % of normal (80% to 120% pre- and postoperative); repeat every 6 to 24 hours until healing is achieved and to maintain desired factor VIII activity concentration. Alternately, use the following formula: Dose (International Units) = Body weight (kg) x Desired Factor VIII Rise (International Units/dL or % of normal) x 0.5 (International Unit/kg per International Unit/dL). Adjust dose based on clinical response.[56320]

Intravenous dosage (Adynovate)

Adults

For minor surgical procedures, including tooth extractions, 30 to 50 International Units/kg/dose IV within 1 hour before surgery to achieve a peak postinfusion 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 within 1 hour before surgery to achieve a peak postinfusion factor VIII activity concentration of 80% to 120% of normal (pre- and postoperative); repeat every 8 to 24 hours until adequate wound healing is achieved and to maintain factor VIII activity concentration 80% to 120% of normal.[60296]

Children and Adolescents 12 to 17 years

Children 1 to 11 years

For minor surgical procedures, including tooth extractions, 30 to 50 International Units/kg/dose IV within 1 hour before surgery to achieve a peak postinfusion 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 within 1 hour before surgery to achieve a peak postinfusion factor VIII activity concentration of 80% to 120% of normal (pre- and postoperative); repeat every 6 to 24 hours until adequate wound healing is achieved and to maintain factor VIII activity concentration 80% to 120% of normal.[60296]

Intravenous dosage (Afstyla)

Adults

For minor surgical procedures, including tooth extractions, 15 to 30 International Units/kg/dose IV to achieve a peak postinfusion 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 postinfusion 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 factor VIII activity concentration of 30% to 60% of normal for another 7 days.

Infants, Children, and Adolescents

Intravenous dosage (Alphanate)

Adults

For tooth extraction, 25 International Units/kg/dose IV for a peak postinfusion factor VIII 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 postinfusion factor VIII activity concentration of 50% to 80% of normal; the factor VIII activity concentration should be maintained at 30% of normal or higher for approximately 2 weeks.

Infants, Children, and Adolescents

Intravenous dosage (Esperoct)

Adults

50 International Units/kg/dose IV. May give additional dose(s) after 24 hours if necessary for minor surgery and every 24 hours for first week and then approximately every 48 hours until wound healing occurs for major surgery. Alternately, to achieve a specific target factor VIII activity concentration, use the following formula: Dose (International Units) = Body Weight (kg) x Desired Factor VIII Increase (International Units/dL or % of normal) x 0.5. Base dose on individual clinical response.[63978]

Children and Adolescents 12 to 17 years

Children 1 to 11 years

65 International Units/kg/dose IV. May give additional dose(s) after 24 hours if necessary for minor surgery and every 24 hours for first week and then approximately every 48 hours until wound healing occurs for major surgery. Alternately, to achieve a specific target factor VIII activity concentration, use the following formula: Dose (International Units) = Body Weight (kg) x Desired Factor VIII Increase (International Units/dL or % of normal) x 0.5. Base dose on individual clinical response.[63978]

Intravenous dosage (Helixate FS, Kogenate FS)

Adults

For minor surgical procedures, including tooth extraction, 15 to 30 International Units/kg/dose IV to achieve a peak postinfusion factor VIII 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 postinfusion factor VIII 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.

Infants, Children, and Adolescents

Intravenous dosage (Hemofil-M, Monarc-M, Recombinate)

Adults

For minor surgical procedures, including tooth extraction, a single infusion of 30 to 40 International Units/kg/dose IV to achieve a peak postinfusion factor VIII 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 postinfusion factor VIII 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.

Infants, Children, and Adolescents

Intravenous dosage (Humate-P)

Adults

For tooth extraction, 25 International Units/kg/dose IV to achieve a peak postinfusion factor VIII 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 factor VIII activity concentration of about 30%; then continue maintenance dose 1 to 2 times daily 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 factor VIII activity concentration of 80% to 100% for 7 days; then continue the dose 1 to 2 times daily to maintain the factor VIII activity concentration at 30% to 50% for 7 days or until adequate healing.

Infants, Children, and Adolescents

Intravenous dosage (Jivi)

Adults

For minor surgical procedures, including tooth extractions, 15 to 30 International Units/kg/dose IV to achieve a peak postinfusion factor VIII activity concentration of 30% to 60% of normal (pre- and post-operative); repeat every 24 hours as necessary until bleeding is resolved. For major surgery, administer 40 to 50 International Units/kg/dose IV to achieve a peak postinfusion factor VIII activity concentration of 80% to 100% of normal (pre- and post-operative); repeat every 12 to 24 hours until adequate wound healing is achieved, then continue for at least 7 days to maintain factor VIII activity concentration 30% to 60% of normal. Max: 6,000 International Units/dose (round to vial size).[63486]

Children and Adolescents 12 to 17 years

For minor surgical procedures, including tooth extractions, 15 to 30 International Units/kg/dose IV to achieve a peak postinfusion factor VIII activity concentration of 30% to 60% of normal (pre- and post-operative); repeat every 24 hours as necessary until bleeding is resolved. For major surgery, administer 40 to 50 International Units/kg/dose IV to achieve a peak postinfusion factor VIII activity concentration of 80% to 100% of normal (pre- and post-operative); repeat every 12 to 24 hours until adequate wound healing is achieved, then continue for at least 7 days to maintain factor VIII activity concentration 30% to 60% of normal. Max: 6,000 International Units/dose (round to vial size).[63486]

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.[61730]

Children and Adolescents

Intravenous dosage (Koate-DVI)

Adults

For major surgical procedures, 50 International Units/kg/dose IV to achieve a peak postinfusion factor VIII 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.

Infants, Children, and Adolescents

Intravenous dosage (Kovaltry)

Adults

For minor surgery (e.g., uncomplicated tooth extraction), 15 to 30 International Units/kg/dose to achieve a peak postinfusion 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 postinfusion 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.[60650]

Infants, Children, and Adolescents

Intravenous dosage (Monoclate-P)

Adults

For minor surgical procedures, 15 to 25 International Units/kg/dose IV to achieve a peak postinfusion factor VIII 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 postinfusion factor VIII 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. Maintain factor VIII concentrations at a daily minimum of at least 30% for a period of 10 to 14 days postoperatively.

Infants, Children, and Adolescents

Intravenous dosage (Novoeight)

Adults

For minor surgical procedures, including tooth extraction, 15 to 30 International Units/kg/dose IV to achieve a peak postinfusion factor VIII 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 postinfusion factor VIII 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 factor VIII activity concentration of 30% to 60% of normal.[56302]

Infants, Children, and Adolescents

For minor surgical procedures, including tooth extraction, 15 to 30 International Units/kg/dose IV to achieve a peak postinfusion factor VIII 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 postinfusion factor VIII 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 factor VIII activity concentration of 30% to 60% of normal.[56302]

Intravenous dosage (Nuwiq)

Adults

For minor surgical procedures, including tooth extractions, 15 to 30 International Units/kg/dose IV to achieve a peak postinfusion 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 postinfusion factor VIII 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 factor VIII activity concentration of 30% to 60% of normal for another 7 days.[60156]

Children and Adolescents 2 to 17 years

For minor surgical procedures, including tooth extractions, 15 to 30 International Units/kg/dose IV to achieve a peak postinfusion 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, 40 to 50 International Units/kg/dose IV to achieve a peak postinfusion factor VIII 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 factor VIII activity concentration of 30% to 60% of normal for another 7 days.[60156]

Intravenous dosage (Xyntha)

Adults

For minor surgical procedures, 15 to 30 International Units/kg/dose IV to achieve a peak postinfusion factor VIII 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 postinfusion factor VIII activity concentration of 60% to 100% of normal; repeat every 8 to 24 hours until hemostasis is achieved.[49402]

Infants, Children, and Adolescents

For minor surgical procedures, 15 to 30 International Units/kg/dose IV to achieve a peak postinfusion factor VIII 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 postinfusion factor VIII activity concentration of 60% to 100% of normal; repeat every 8 to 24 hours until hemostasis is achieved.[49402]

For routine bleeding prophylaxis to reduce the frequency of bleeding episodes in patients with hemophilia A

NOTE: Factor VIII concentration may be expressed as % or International Units/dL.

Intravenous dosage (Advate)

Adults

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 dose based on clinical response.[56320]

Infants, Children, and Adolescents

Intravenous dosage (Adynovate)

Adults

40 to 50 International Units/kg/dose IV 2 times weekly. Adjust dose based on clinical response.[60296]

Children and Adolescents 12 to 17 years

40 to 50 International Units/kg/dose IV 2 times weekly. Adjust dose based on clinical response.[60296]

Children 1 to 11 years

55 to 70 International Units/kg/dose IV 2 times weekly. Adjust dose based on clinical response.[60296]

Intravenous dosage (Afstyla)

Adults

20 to 50 International Units/kg/dose IV 2 to 3 times weekly. Adjust dose based on clinical response.[60830]

Children and Adolescents 12 to 17 years

20 to 50 International Units/kg/dose IV 2 to 3 times weekly. Adjust dose based on clinical response.[60830]

Infants and Children younger than 12 years

30 to 50 International Units/kg/dose IV 2 to 3 times weekly. Adjust dose based on clinical response.[60830]

Intravenous dosage (Esperoct)

Adults

50 International Units/kg/dose IV every 4 days. Adjust dosing frequency based on bleeding episodes.[63978]

Children and Adolescents 12 to 17 years

50 International Units/kg/dose IV every 4 days. Adjust dosing frequency based on bleeding episodes.[63978]

Children 1 to 11 years

65 International Units/kg/dose IV twice weekly. Adjust dosing frequency based on bleeding episodes.[63978]

Intravenous dosage (Jivi)

Adults

30 to 40 International Units/kg IV twice weekly. May adjust to 45 to 60 International Units/kg IV every 5 days and further individually adjust to less or more frequent dosing based on bleeding episodes. Max: 6,000 International Units/dose (round to vial size).[63486]

Children and Adolescents 12 to 17 years

Intravenous dosage (Kogenate FS)

Adults

25 International Units/kg IV/dose 3 times per week.[56366]

Infants, Children, and Adolescents

25 International Units/kg/dose IV every other day.[56366]

Intravenous dosage (Kovaltry)

Adults

20 to 40 International Units/kg/dose IV 2 or 3 times weekly. Adjust dose based on clinical response.[60650]

Adolescents

20 to 40 International Units/kg/dose IV 2 or 3 times weekly. Adjust dose based on clinical response.[60650]

Infants and Children

25 to 50 International Units/kg/dose IV 2 times weekly, 3 times weekly, or every other day. Adjust dose based on clinical response.[60650]

Intravenous dosage (Novoeight)

Adults

20 to 50 International Units/kg/dose IV 3 times weekly or 20 to 40 International Units/kg/dose IV every other day.[56302]

Children and Adolescents 12 to 17 years

20 to 50 International Units/kg/dose IV 3 times weekly or 20 to 40 International Units/kg/dose IV every other day.[56302]

Infants and Children 1 month to 11 years

25 to 60 International Units/kg/dose IV 3 times weekly or 25 to 50 International Units/kg/dose IV every other day.[56302]

Intravenous dosage (Nuwiq)

Adults

30 to 40 International Units/kg/dose IV every other day.[60156]

Children and Adolescents 12 to 17 years

30 to 40 International Units/kg/dose IV every other day.[60156]

Children 2 to 11 years

30 to 50 International Units/kg/dose IV every other day or 3 times weekly.[60156]

Intravenous dosage (Wilate)

Adults

20 to 40 International Units/kg/dose IV every 2 to 3 days. Adjust dose based on clinical response.[56305]

Adolescents

20 to 40 International Units/kg/dose IV every 2 to 3 days. Adjust dose based on clinical response.[56305]

Intravenous dosage (Xyntha)

Adults

30 International Units/kg/dose IV 3 times weekly. Adjust dose based on individual response.[49402]

Children and Adolescents 12 to 17 years

30 International Units/kg/dose IV 3 times weekly. Adjust dose based on individual response.[49402]

Children 1 to 11 years

25 International Units/kg/dose IV every other day. Adjust dose based on individual response. Compared to older children and adults, children younger than 12 years may require a higher dose per kg body weight and/or more frequent dosing due to higher clearance.[49402]

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 an orphan drug for this indication.

Intravenous dosage (Humate-P general dosing)

Adults

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.[56306]

Infants, Children, and Adolescents

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

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.[56306]

Infants, Children, and Adolescents

Intravenous dosage (Wilate)

Adults

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.[56305]

Infants, Children, and Adolescents

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

40 to 50 International Units vWF:RCo/kg/dose (17 to 20 International Units/kg Humate-P) IV for 1 to 2 doses.[56306]

Infants, Children, and Adolescents

40 to 50 International Units vWF:RCo/kg/dose (17 to 20 International Units/kg Humate-P) IV for 1 to 2 doses.[56306]

Intravenous dosage (Wilate)

Adults

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%.[56305]

Infants, Children, and Adolescents

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

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.[56306]

Infants, Children, and Adolescents

Intravenous dosage (Wilate)

Adults

Infants, Children, and Adolescents

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

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.[56306]

Infants, Children, and Adolescents

Intravenous dosage (Wilate)

Adults

Infants, Children, and Adolescents

for routine bleeding prophylaxis to reduce the frequency of bleeding episodes in vWD

Intravenous dosage (Wilate)

Adults

20 to 40 International Units/kg/dose IV 2 to 3 times per week. Exact dosing should be defined by the severity of vWD and by the person's clinical status and response.[56305]

Children and Adolescents 6 to 17 years

20 to 40 International Units/kg/dose IV 2 to 3 times per week. Exact dosing should be defined by the severity of vWD and by the person's clinical status and response.[56305]

for surgical bleeding prophylaxis during major or minor procedures in patients with vWD in whom desmopressin is either ineffective or contraindicated

Intravenous dosage (Alphanate)

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.[56307]

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.[56307]

Intravenous dosage (Humate-P)

Adults

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:RCo baseline) / 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 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/dLper 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.[56306]

Infants, Children, and Adolescents

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:RCo_{30 min} - Plasma vWF:RCo_baseline) / 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.[56306]

Intravenous dosage (Wilate)

Adults

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.[56305]

Infants, Children, and Adolescents

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:RCo_{30 min} - Plasma vWF:RCo_baseline) / 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.[56305]

Therapeutic Drug Monitoring

Monitor plasma factor VIII activity by performing a validated one-stage clotting or chromogenic assay to confirm adequate concentrations of factor VIII have been achieved and maintained.[56305] [56332] [60830] [61730]
- Monitor factor VIII activity 15 to 30 minutes and 3 hours after the initial dose.
- Monitor factor VIII activity 15 to 30 minutes after subsequent doses.[55323] [58255]
One-stage clotting assay results can be affected by the type of aPTT reagent used. Some silica-based aPTT reagents underestimate the activity of factor VIII by up to 60%; other reagents including those with kaolin-based activators may overestimate activity by 20%. If an appropriate one-stage clotting or chromogenic assay is not available locally, use a reference laboratory.[60830] [63486] [63978]
In patients with von Willebrand's disease (vWD), monitor trough plasma vWF:RCo and factor VIII activities at least once daily. Sustained excessive vWF and factor VIII activity concentrations increase the risk of thrombotic events.[56305] [56306] [56307] Guidelines recommend not exceeding vWF:RCo concentrations of 200 International Units/dL and factor VIII concentrations of 250 to 300 International Units/dL.[64325]
Monitor for the development of factor VIII inhibitors, and vWF inhibitors if applicable.
Perform a Nijmegen-modified Bethesda assay to determine whether factor VIII inhibitors are present. Use Bethesda Units (BU) to report inhibitor concentrations.[55323] [56305] [56332] [60830] [61730]
- An inhibitor titer of 0.6 BU/mL or more is considered clinically significant.
- A low-responding inhibitor is defined by a concentration persistently less than 5 BU/mL.
- A high-responding inhibitor id defined by a concentration of 5 BU/mL or more.[55323]
Assays for detecting vWF inhibitors are not as well-established.[64325]

Maximum Dosage Limits

Patients with Hepatic Impairment Dosing

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

Patients with Renal Impairment Dosing

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

† Off-label indication

Revision Date: 03/07/2024, 05:11:40 PM

References

25743 - Bona RD, Weinstein RA, Weisman SJ, et al. The use of continuous infusion of factor concentrates in the treatment of hemophilia. Am J Hematol 1989;32:8-13.32317 - Hemophilia of Georgia, U.S.A. Protocols for the treatment of haemophilia and von Willebrand disease. Haemophilia 2000;6(Suppl 1):84-93.49402 - Xyntha (antihemophilic factor [recombinant]) package insert. Philadelphia, PA: Wyeth Pharmaceuticals Inc.; 2020 Aug.55323 - Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al. Guidelines for the management of hemophilia. Haemophilia 2013;19:e1-e47.56302 - Novoeight (antihemophilic factor [recombinant]) package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2018 Dec.56305 - Wilate (von Willebrand factor/coagulation factor VIII complex, human) package insert. Paramus, NJ: Octapharma USA Inc.; 2024 Nov.56306 - Humate-P (antihemophilic factor/von Willebrand factor complex, human) package insert. Kankakee, IL: CSL Behring LLC; 2017 Sept.56307 - Alphanate (antihemophilic factor/von Willebrand factor complex, human) package insert. Los Angeles, CA: Grifols Biologicals Inc.; 2017 Mar.56320 - Advate (antihemophilic factor [recombinant]) package insert. Lexington, MA: Baxalta US Inc; 2018 Dec.56325 - Recombinate (antihemophilic factor [recombinant]) package insert. Westlake Village, CA: Baxalta US Inc.; 2018 Jun.56332 - Hemofil M (antihemophilic factor [human], method M) package insert. Lexington, MA: Baxalta US Inc.; 2018 Jun.56366 - Kogenate FS (antihemophilic factor [recombinant]) package insert. Tarrytown, NY: Bayer HealthCare LLC; 2016 May.58255 - Obizur (antihemophilic factor [recombinant], porcine sequence) package insert. Lexington, MA: Baxalta US Inc.; 2023 Feb.60156 - Nuwiq (antihemophilic factor [recombinant]) package insert. Hoboken, NJ: Octapharma USA, Inc.; 2020 Sept.60296 - Adynovate (antihemophilic factor [recombinant], PEGylated) package insert. Lexington, MA: Takeda Pharmaceuticals U.S.A., Inc.; 2023 Aug.60650 - Kovaltry (antihemophilic factor [recombinant]) package insert. Whippany, NJ: Bayer Healthcare LLC; 2021 Oct.60830 - Afstyla (antihemophilic factor [recombinant], single chain) package insert. Kankakee, Il: CSL Behring LLC; 2023 Jun.61730 - Koate (antihemophilic factor [human]) package insert. Deerfield, IL: Baxter Healthcare Corporation; 2018 Jun.63486 - JIVI [antihemophilic factor (recombinant), PEGylated-aucl] package insert. Whippany, NJ: Bayer HealthCare LLC; 2018 Aug.63978 - Esperoct (antihemophilic factor [recombinant], glycopegylated-exei) lyophilized powder for solution package insert. Plainsboro, NJ; Novo Nordisk Inc.: 2024 Feb.64325 - National Heart, Lung, and Blood Institute (NHLBI). Diagnosis, evaluation, and management of von Willebrand disease. NIH Publication No. 08-5832. US Department of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute;2007.

How Supplied

Antihemophilic Factor , Glycopegylated Powder for solution for injection

ESPEROCT 1000 International Units Powder for Injection (00169-8100) (Novo Nordisk Inc.) null

Antihemophilic Factor , Glycopegylated Powder for solution for injection

ESPEROCT 1500 International Units Powder for Injection (00169-8150) (Novo Nordisk Inc.) null

Antihemophilic Factor , Glycopegylated Powder for solution for injection

ESPEROCT 2000 International Units Powder for Injection (00169-8200) (Novo Nordisk Inc.) null

Antihemophilic Factor , Glycopegylated Powder for solution for injection

ESPEROCT 3000 International Units Powder for Injection (00169-8300) (Novo Nordisk Inc.) null

Antihemophilic Factor , Glycopegylated Powder for solution for injection

ESPEROCT 500 International Units Powder for Injection (00169-8500) (Novo Nordisk Inc.) null

Antihemophilic Factor , PEGylated Lyophilisate for solution for injection

Adynovate 1000units Powder for Injection (00944-4624) (Baxalta Inc, a Shire Company) null

Antihemophilic Factor , PEGylated Lyophilisate for solution for injection

Adynovate 1000units Powder for Injection (00944-4256) (Baxalta Inc, a Shire Company) (off market)

Antihemophilic Factor , PEGylated Lyophilisate for solution for injection

Adynovate 1500units Powder for Injection (00944-4627) (Baxalta Inc, a Shire Company) null

Antihemophilic Factor , PEGylated Lyophilisate for solution for injection

Adynovate 2000units Powder for Injection (00944-4625) (Baxalta Inc, a Shire Company) null

Antihemophilic Factor , PEGylated Lyophilisate for solution for injection

Adynovate 2000units Powder for Injection (00944-4258) (Baxalta Inc, a Shire Company) (off market)

Antihemophilic Factor , PEGylated Lyophilisate for solution for injection

Adynovate 250units Powder for Injection (00944-4622) (Baxalta Inc, a Shire Company) null

Antihemophilic Factor , PEGylated Lyophilisate for solution for injection

Adynovate 250units Powder for Injection (00944-4252) (Baxalta Inc, a Shire Company) (off market)

Antihemophilic Factor , PEGylated Lyophilisate for solution for injection

Adynovate 3000units Powder for Injection (00944-4628) (Baxalta Inc, a Shire Company) null

Antihemophilic Factor , PEGylated Lyophilisate for solution for injection

Adynovate 500units Powder for Injection (00944-4623) (Baxalta Inc, a Shire Company) null

Antihemophilic Factor , PEGylated Lyophilisate for solution for injection

Adynovate 500units Powder for Injection (00944-4254) (Baxalta Inc, a Shire Company) (off market)

Antihemophilic Factor , PEGylated Lyophilisate for solution for injection

Adynovate 750units Powder for Injection (00944-4626) (Baxalta Inc, a Shire Company) null

Antihemophilic Factor , PEGylated Lyophilisate for solution for injection

Jivi 1000units Powder for Injection (00026-3944) (Bayer Pharmaceuticals Corporation) null

Antihemophilic Factor , PEGylated Lyophilisate for solution for injection

Jivi 2000units Powder for Injection (00026-3946) (Bayer Pharmaceuticals Corporation) null

Antihemophilic Factor , PEGylated Lyophilisate for solution for injection

Jivi 3000units Powder for Injection (00026-3948) (Bayer Pharmaceuticals Corporation) null

Antihemophilic Factor , PEGylated Lyophilisate for solution for injection

Jivi 500units Powder for Injection (00026-3942) (Bayer Pharmaceuticals Corporation) null

Antihemophilic Factor VIII Lyophilisate for solution for injection

Bioclate 1000units Powder for Injection (00053-8110) (CSL Behring) (off market)

Antihemophilic Factor VIII Lyophilisate for solution for injection

Bioclate 250units Powder for Injection (00053-8110) (CSL Behring) (off market)

Antihemophilic Factor VIII Lyophilisate for solution for injection

Bioclate 500units Powder for Injection (00053-8110) (CSL Behring) (off market)

Antihemophilic Factor VIII Powder for solution for injection

Recombinate 1000units Powder for Injection (00944-2938) (Baxalta Inc, a Shire Company) (off market)

Antihemophilic Factor VIII Powder for solution for injection

Recombinate 250units Powder for Injection (00944-2938) (Baxalta Inc, a Shire Company) (off market)

Antihemophilic Factor VIII Powder for solution for injection

Recombinate 500units Powder for Injection (00944-2938) (Baxalta Inc, a Shire Company) (off market)

Antihemophilic Factor VIII Powder for solution for injection

Recombinate Powder for Injection (00944-2833) (Baxalta Inc, a Shire Company) (off market)

Antihemophilic Factor VIII Powder for solution for injection

Recombinate Powder for Injection (00944-2831) (Baxalta Inc, a Shire Company) (off market)

Antihemophilic Factor VIII Powder for solution for injection

Recombinate Powder for Injection (00944-2832) (Baxalta Inc, a Shire Company) (off market)

Antihemophilic Factor VIII Powder for solution for injection

Recombinate Powder for Injection (00944-2835) (Baxalta Inc, a Shire Company) null

Antihemophilic Factor VIII Powder for solution for injection

Recombinate Powder for Injection (00944-2834) (Baxalta Inc, a Shire Company) null

Antihemophilic Factor VIII Powder for solution for injection

Recombinate Powder for Injection ( 801-1240units) (00944-2843) (Baxalta Inc, a Shire Company) null

Antihemophilic Factor VIII Powder for solution for injection

Recombinate Powder for Injection (1241-1800units) (00944-2844) (Baxalta Inc, a Shire Company) null

Recombinate Powder for Injection (1241-1800units) package photo

Antihemophilic Factor VIII Powder for solution for injection

Recombinate Powder for Injection (1801-2400units) (00944-2845) (Baxalta Inc, a Shire Company) null

Antihemophilic Factor VIII Powder for solution for injection

Recombinate Powder for Injection (220-400units) (00944-2841) (Baxalta Inc, a Shire Company) null

Antihemophilic Factor VIII Powder for solution for injection

Recombinate Powder for Injection (401-800units) (00944-2842) (Baxalta Inc, a Shire Company) null

Antihemophilic Factor VIII Lyophilisate for solution for injection

Kogenate FS 1000units Powder for Injection (00026-0372) (Bayer Pharmaceuticals Corporation) (off market)

Antihemophilic Factor VIII Lyophilisate for solution for injection

Kogenate FS 1000units Powder for Injection (00026-3785) (Bayer Pharmaceuticals Corporation) (off market)

Antihemophilic Factor VIII Lyophilisate for solution for injection

Kogenate FS 2000units Powder for Injection (00026-3786) (Bayer Pharmaceuticals Corporation) (off market)

Antihemophilic Factor VIII Lyophilisate for solution for injection

Kogenate FS 250units Powder for Injection (00026-0372) (Bayer Pharmaceuticals Corporation) (off market)

Antihemophilic Factor VIII Lyophilisate for solution for injection

Kogenate FS 250units Powder for Injection (00026-3782) (Bayer Pharmaceuticals Corporation) (off market)

Antihemophilic Factor VIII Lyophilisate for solution for injection

Kogenate FS 3000units Powder for Injection (00026-3787) (Bayer Pharmaceuticals Corporation) (off market)

Antihemophilic Factor VIII Lyophilisate for solution for injection

Kogenate FS 500units Powder for Injection (00026-0372) (Bayer Pharmaceuticals Corporation) (off market)

Antihemophilic Factor VIII Lyophilisate for solution for injection

Kogenate FS 500units Powder for Injection (00026-3783) (Bayer Pharmaceuticals Corporation) (off market)

Antihemophilic Factor VIII Lyophilisate for solution for injection

Kogenate FS with Bio-Set 1000units Powder for Injection (00026-3795) (Bayer Pharmaceuticals Corporation) (off market)

Antihemophilic Factor VIII Lyophilisate for solution for injection

Kogenate FS with Bio-Set 1000units Powder for Injection (00026-0379) (Bayer Pharmaceuticals Corporation) (off market)

Antihemophilic Factor VIII Lyophilisate for solution for injection

Kogenate FS with Bio-Set 2000units Powder for Injection (00026-3796) (Bayer Pharmaceuticals Corporation) (off market)

Antihemophilic Factor VIII Lyophilisate for solution for injection

Kogenate FS with Bio-Set 250units Powder for Injection (00026-3792) (Bayer Pharmaceuticals Corporation) (off market)

Antihemophilic Factor VIII Lyophilisate for solution for injection

Kogenate FS with Bio-Set 250units Powder for Injection (00026-0379) (Bayer Pharmaceuticals Corporation) (off market)

Antihemophilic Factor VIII Lyophilisate for solution for injection

Kogenate FS with Bio-Set 3000units Powder for Injection (00026-3797) (Bayer Pharmaceuticals Corporation) (off market)

Antihemophilic Factor VIII Lyophilisate for solution for injection

Kogenate FS with Bio-Set 500units Powder for Injection (00026-3793) (Bayer Pharmaceuticals Corporation) (off market)

Antihemophilic Factor VIII Lyophilisate for solution for injection

Kogenate FS with Bio-Set 500units Powder for Injection (00026-0379) (Bayer Pharmaceuticals Corporation) (off market)

Antihemophilic Factor VIII Lyophilisate for solution for injection

Kogenate FS with Vial Adaptor 1000units Powder for Injection (00026-3785) (Bayer Pharmaceuticals Corporation) null

Antihemophilic Factor VIII Lyophilisate for solution for injection

Kogenate FS with Vial Adaptor 2000units Powder for Injection (00026-3786) (Bayer Pharmaceuticals Corporation) null

Antihemophilic Factor VIII Lyophilisate for solution for injection

Kogenate FS with Vial Adaptor 250units Powder for Injection (00026-3782) (Bayer Pharmaceuticals Corporation) null

Antihemophilic Factor VIII Lyophilisate for solution for injection

Kogenate FS with Vial Adaptor 3000units Powder for Injection (00026-3787) (Bayer Pharmaceuticals Corporation) null

Antihemophilic Factor VIII Lyophilisate for solution for injection

Kogenate FS with Vial Adaptor 500units Powder for Injection (00026-3783) (Bayer Pharmaceuticals Corporation) null

Antihemophilic Factor VIII Powder for solution for injection

AFSTYLA 1000units Powder for Injection (69911-0476) (CSL Behring) null

Antihemophilic Factor VIII Powder for solution for injection

AFSTYLA 1500units Powder for Injection (69911-0480) (CSL Behring) null

Antihemophilic Factor VIII Powder for solution for injection

AFSTYLA 2000units Powder for Injection (69911-0477) (CSL Behring) null

Antihemophilic Factor VIII Powder for solution for injection

AFSTYLA 2500units Powder for Injection (69911-0481) (CSL Behring) null

Antihemophilic Factor VIII Powder for solution for injection

AFSTYLA 250units Powder for Injection (69911-0474) (CSL Behring) null

Antihemophilic Factor VIII Powder for solution for injection

AFSTYLA 3000units Powder for Injection (69911-0478) (CSL Behring) null

Antihemophilic Factor VIII Powder for solution for injection

AFSTYLA 500units Powder for Injection (69911-0475) (CSL Behring) null

Antihemophilic Factor VIII Powder for solution for injection

Helixate 1000units Powder for Injection (00053-8120) (CSL Behring) (off market)

Antihemophilic Factor VIII Powder for solution for injection

Helixate 250units Powder for Injection (00053-8120) (CSL Behring) (off market)

Antihemophilic Factor VIII Powder for solution for injection

Helixate 500units Powder for Injection (00053-8120) (CSL Behring) (off market)

Antihemophilic Factor VIII Powder for solution for injection

Helixate FS 1000units Powder for Injection (00053-8130) (CSL Behring) (off market)

Antihemophilic Factor VIII Powder for solution for injection

Helixate FS 1000units Powder for Injection (00053-8133) (CSL Behring) (off market)

Antihemophilic Factor VIII Powder for solution for injection

Helixate FS 2000units Powder for Injection (00053-8134) (CSL Behring) (off market)

Antihemophilic Factor VIII Powder for solution for injection

Helixate FS 250units Powder for Injection (00053-8130) (CSL Behring) (off market)

Antihemophilic Factor VIII Powder for solution for injection

Helixate FS 250units Powder for Injection (00053-8131) (CSL Behring) (off market)

Antihemophilic Factor VIII Powder for solution for injection

Helixate FS 3000units Powder for Injection (00053-8135) (CSL Behring) (off market)

Antihemophilic Factor VIII Powder for solution for injection

Helixate FS 500units Powder for Injection (00053-8130) (CSL Behring) (off market)

Antihemophilic Factor VIII Powder for solution for injection

Helixate FS 500units Powder for Injection (00053-8132) (CSL Behring) (off market)

Antihemophilic Factor VIII Powder for solution for injection

Kogenate 1000units Powder for Injection (00026-0670) (Bayer Pharmaceuticals Corporation) (off market)

Antihemophilic Factor VIII Powder for solution for injection

Kogenate 250units Powder for Injection (00026-0670) (Bayer Pharmaceuticals Corporation) (off market)

Antihemophilic Factor VIII Powder for solution for injection

Kogenate 500units Powder for Injection (00026-0670) (Bayer Pharmaceuticals Corporation) (off market)

Antihemophilic Factor VIII Powder for solution for injection

Kovaltry 1000units Powder for Injection (00026-3824) (Bayer Pharmaceuticals Corporation) null

Antihemophilic Factor VIII Powder for solution for injection

Kovaltry 2000units Powder for Injection (00026-3826) (Bayer Pharmaceuticals Corporation) null

Antihemophilic Factor VIII Powder for solution for injection

Kovaltry 250units Powder for Injection (00026-3821) (Bayer Pharmaceuticals Corporation) null

Antihemophilic Factor VIII Powder for solution for injection

Kovaltry 3000units Powder for Injection (00026-3828) (Bayer Pharmaceuticals Corporation) null

Antihemophilic Factor VIII Powder for solution for injection

Kovaltry 500units Powder for Injection (00026-3822) (Bayer Pharmaceuticals Corporation) null

Antihemophilic Factor VIII Powder for solution for injection

Novoeight 250units Powder for Injection (00169-7825) (Novo Nordisk Inc.) null

Antihemophilic Factor VIII Powder for solution for injection

Novoeight 500units Powder for Injection (00169-7850) (Novo Nordisk Inc.) null

Antihemophilic Factor VIII Powder for solution for injection

Novoeight 1000units Powder for Injection (00169-7810) (Novo Nordisk Inc.) null

Antihemophilic Factor VIII Powder for solution for injection

Novoeight 1500units Powder for Injection (00169-7815) (Novo Nordisk Inc.) null

Antihemophilic Factor VIII Powder for solution for injection

Novoeight 2000units Powder for Injection (00169-7820) (Novo Nordisk Inc.) null

Antihemophilic Factor VIII Powder for solution for injection

Novoeight 3000units Powder for Injection (00169-7830) (Novo Nordisk Inc.) null

Antihemophilic Factor VIII Lyophilisate for solution for injection

Alphanate 1000units-1500units Powder for Injection (68516-4600) (Grifols USA, LLC) (off market)

Antihemophilic Factor VIII Lyophilisate for solution for injection

Alphanate 1000units-1500units Powder for Injection (49669-4600) (Grifols USA, LLC) (off market)

Antihemophilic Factor VIII Lyophilisate for solution for injection

Alphanate 250units-500units Powder for Injection (68516-4600) (Grifols USA, LLC) (off market)

Antihemophilic Factor VIII Lyophilisate for solution for injection

Alphanate 250units-500units Powder for Injection (49669-4600) (Grifols USA, LLC) (off market)

Antihemophilic Factor VIII Lyophilisate for solution for injection

Koate 1000units Powder for Injection (76125-0676) (Kedrion Biopharma Inc) null

Antihemophilic Factor VIII Lyophilisate for solution for injection

Koate 1000units Powder for Injection (76125-0678) (Kedrion Biopharma Inc) null

Antihemophilic Factor VIII Lyophilisate for solution for injection

Koate 1000units Powder for Injection (76125-0679) (Kedrion Biopharma Inc) null

Antihemophilic Factor VIII Lyophilisate for solution for injection

Koate 250units Powder for Injection (76125-0256) (Kedrion Biopharma Inc) null

Antihemophilic Factor VIII Lyophilisate for solution for injection

Koate 250units Powder for Injection (76125-0257) (Kedrion Biopharma Inc) null

Antihemophilic Factor VIII Lyophilisate for solution for injection

Koate 250units Powder for Injection (76125-0259) (Kedrion Biopharma Inc) null

Antihemophilic Factor VIII Lyophilisate for solution for injection

Koate 500units Powder for Injection (76125-0668) (Kedrion Biopharma Inc) null

Antihemophilic Factor VIII Lyophilisate for solution for injection

Koate 500units Powder for Injection (76125-0663) (Kedrion Biopharma Inc) null

Antihemophilic Factor VIII Lyophilisate for solution for injection

Koate 500units Powder for Injection (76125-0665) (Kedrion Biopharma Inc) null

Antihemophilic Factor VIII , Double Viral Inactivation Powder for solution for injection

Koate-DVI 1000units Powder for Injection (00026-0665) (Bayer Pharmaceuticals Corporation) (off market)

Antihemophilic Factor VIII , Double Viral Inactivation Powder for solution for injection

Koate-DVI 1000units Powder for Injection (13533-0665) (Grifols USA, LLC) (off market)

Antihemophilic Factor VIII , Double Viral Inactivation Powder for solution for injection

Koate-DVI 1000units Powder for Injection (76125-0667) (Kedrion Biopharma Inc) (off market)

Antihemophilic Factor VIII , Double Viral Inactivation Powder for solution for injection

Koate-DVI 1000units Powder for Injection (13533-0665) (Kedrion Biopharma Inc) (off market)

Antihemophilic Factor VIII , Double Viral Inactivation Powder for solution for injection

Koate-DVI 1000units Powder for Injection (76125-0672) (Kedrion Biopharma Inc) null

Antihemophilic Factor VIII , Double Viral Inactivation Powder for solution for injection

Koate-DVI 1000units Powder for Injection (76125-0673) (Kedrion Biopharma Inc) null

Antihemophilic Factor VIII , Double Viral Inactivation Powder for solution for injection

Koate-DVI 250units Powder for Injection (00026-0665) (Bayer Pharmaceuticals Corporation) (off market)

Antihemophilic Factor VIII , Double Viral Inactivation Powder for solution for injection

Koate-DVI 250units Powder for Injection (13533-0665) (Grifols USA, LLC) (off market)

Antihemophilic Factor VIII , Double Viral Inactivation Powder for solution for injection

Koate-DVI 250units Powder for Injection (76125-0250) (Kedrion Biopharma Inc) null

Antihemophilic Factor VIII , Double Viral Inactivation Powder for solution for injection

Koate-DVI 250units Powder for Injection (13533-0665) (Kedrion Biopharma Inc) (off market)

Antihemophilic Factor VIII , Double Viral Inactivation Powder for solution for injection

Koate-DVI 500units Powder for Injection (00026-0665) (Bayer Pharmaceuticals Corporation) (off market)

Antihemophilic Factor VIII , Double Viral Inactivation Powder for solution for injection

Koate-DVI 500units Powder for Injection (13533-0665) (Grifols USA, LLC) (off market)

Antihemophilic Factor VIII , Double Viral Inactivation Powder for solution for injection

Koate-DVI 500units Powder for Injection (76125-0500) (Kedrion Biopharma Inc) (off market)

Antihemophilic Factor VIII , Double Viral Inactivation Powder for solution for injection

Koate-DVI 500units Powder for Injection (13533-0665) (Kedrion Biopharma Inc) (off market)

Antihemophilic Factor VIII , Double Viral Inactivation Powder for solution for injection

Koate-DVI 500units Powder for Injection (76125-0667) (Kedrion Biopharma Inc) null

Koate-DVI 500units Powder for Injection package photo

Antihemophilic Factor VIII , Method M, Monoclonal Antibody Purified Powder for solution for injection

Hemofil M Powder for Injection (1000units) (00944-3944) (Baxalta Inc, a Shire Company) null

Antihemophilic Factor VIII , Method M, Monoclonal Antibody Purified Powder for solution for injection

Hemofil M Powder for Injection (1700units) (00944-3946) (Baxalta Inc, a Shire Company) null

Antihemophilic Factor VIII , Method M, Monoclonal Antibody Purified Powder for solution for injection

Hemofil M Powder for Injection (1701-2000units) (00944-2935) (Baxalta Inc, a Shire Company) (off market)

Antihemophilic Factor VIII , Method M, Monoclonal Antibody Purified Powder for solution for injection

Hemofil M Powder for Injection (1701-2000units) (00944-2933) (Baxalta Inc, a Shire Company) (off market)

Antihemophilic Factor VIII , Method M, Monoclonal Antibody Purified Powder for solution for injection

Hemofil M Powder for Injection (220-400units) (00944-2935) (Baxalta Inc, a Shire Company) (off market)

Antihemophilic Factor VIII , Method M, Monoclonal Antibody Purified Powder for solution for injection

Hemofil M Powder for Injection (220-400units) (00944-2930) (Baxalta Inc, a Shire Company) (off market)

Antihemophilic Factor VIII , Method M, Monoclonal Antibody Purified Powder for solution for injection

Hemofil M Powder for Injection (250units) (00944-3940) (Baxalta Inc, a Shire Company) null

Antihemophilic Factor VIII , Method M, Monoclonal Antibody Purified Powder for solution for injection

Hemofil M Powder for Injection (401-800units) (00944-2935) (Baxalta Inc, a Shire Company) (off market)

Antihemophilic Factor VIII , Method M, Monoclonal Antibody Purified Powder for solution for injection

Hemofil M Powder for Injection (401-800units) (00944-2931) (Baxalta Inc, a Shire Company) (off market)

Antihemophilic Factor VIII , Method M, Monoclonal Antibody Purified Powder for solution for injection

Hemofil M Powder for Injection (500units) (00944-3942) (Baxalta Inc, a Shire Company) null

Antihemophilic Factor VIII , Method M, Monoclonal Antibody Purified Powder for solution for injection

Hemofil M Powder for Injection (801-1700units) (00944-2935) (Baxalta Inc, a Shire Company) (off market)

Antihemophilic Factor VIII , Method M, Monoclonal Antibody Purified Powder for solution for injection

Hemofil M Powder for Injection (801-1700units) (00944-2932) (Baxalta Inc, a Shire Company) (off market)

Antihemophilic Factor VIII , Method M, Monoclonal Antibody Purified Powder for solution for injection

Monarc-M Powder for Injection (52769-0460) (American National Red Cross) (off market)

Antihemophilic Factor VIII , Method M, Monoclonal Antibody Purified Powder for solution for injection

Monarc-M Powder for Injection (1701-2000units) (00944-1304) (Baxalta Inc, a Shire Company) (off market)

Antihemophilic Factor VIII , Method M, Monoclonal Antibody Purified Powder for solution for injection

Monarc-M Powder for Injection (220-400units) (00944-1301) (Baxalta Inc, a Shire Company) (off market)

Antihemophilic Factor VIII , Method M, Monoclonal Antibody Purified Powder for solution for injection

Monarc-M Powder for Injection (401-800units) (00944-1302) (Baxalta Inc, a Shire Company) (off market)

Antihemophilic Factor VIII , Method M, Monoclonal Antibody Purified Powder for solution for injection

Monarc-M Powder for Injection (801-1700units) (00944-1303) (Baxalta Inc, a Shire Company) (off market)

Antihemophilic Factor VIII , Pasteurized, Monoclonal Antibody Purified Lyophilisate for solution for injection

Monoclate-P (Murine) 1000units (HIGH) Powder for Injection (00053-7633) (CSL Behring) (off market)

Antihemophilic Factor VIII , Pasteurized, Monoclonal Antibody Purified Lyophilisate for solution for injection

Monoclate-P (Murine) 1000units Powder for Injection (00053-7656) (CSL Behring) (off market)

Antihemophilic Factor VIII , Pasteurized, Monoclonal Antibody Purified Lyophilisate for solution for injection

Monoclate-P (Murine) 1500units (SUPER HIGH) Powder for Injection (00053-7634) (CSL Behring) (off market)

Antihemophilic Factor VIII , Pasteurized, Monoclonal Antibody Purified Lyophilisate for solution for injection

Monoclate-P (Murine) 1500units Powder for Injection (00053-7656) (CSL Behring) (off market)

Antihemophilic Factor VIII , Pasteurized, Monoclonal Antibody Purified Lyophilisate for solution for injection

Monoclate-P (Murine) 250units Powder for Injection (00053-7656) (CSL Behring) (off market)

Antihemophilic Factor VIII , Pasteurized, Monoclonal Antibody Purified Lyophilisate for solution for injection

Monoclate-P (Murine) 500units Powder for Injection (00053-7656) (CSL Behring) (off market)

Antihemophilic Factor VIII B-Domain Deleted Powder for solution for injection

ReFacto 1000units Powder for Injection (58394-0005) (Wyeth Biopharma, a subsidiary of Pfizer Inc) (off market)

Antihemophilic Factor VIII B-Domain Deleted Powder for solution for injection

ReFacto 1000units Powder for Injection (58394-0005) (Wyeth Biopharma, a subsidiary of Pfizer Inc) (off market)

Antihemophilic Factor VIII B-Domain Deleted Powder for solution for injection

ReFacto 2000units Powder for Injection (58394-0011) (Wyeth Biopharma, a subsidiary of Pfizer Inc) (off market)

Antihemophilic Factor VIII B-Domain Deleted Powder for solution for injection

ReFacto 2000units Powder for Injection (58394-0011) (Wyeth Biopharma, a subsidiary of Pfizer Inc) (off market)

Antihemophilic Factor VIII B-Domain Deleted Powder for solution for injection

ReFacto 250units Powder for Injection (58394-0007) (Wyeth Biopharma, a subsidiary of Pfizer Inc) (off market)

Antihemophilic Factor VIII B-Domain Deleted Powder for solution for injection

ReFacto 250units Powder for Injection (58394-0007) (Wyeth Biopharma, a subsidiary of Pfizer Inc) (off market)

Antihemophilic Factor VIII B-Domain Deleted Powder for solution for injection

ReFacto 500units Powder for Injection (58394-0006) (Wyeth Biopharma, a subsidiary of Pfizer Inc) (off market)

Antihemophilic Factor VIII B-Domain Deleted Powder for solution for injection

ReFacto 500units Powder for Injection (58394-0006) (Wyeth Biopharma, a subsidiary of Pfizer Inc) (off market)

Antihemophilic Factor VIII B-Domain Deleted (HEK) Powder for solution for injection

Nuwiq 1000units Powder for Injection (68982-0143) (Octapharma USA Inc.) null

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Advate 1000units Powder for Injection (00944-2940) (Baxalta Inc, a Shire Company) (off market)

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Description/Classification

Description

Antihemophilic factor (AHF), also known as factor VIII, is a parenteral coagulation factor indicated for perioperative management and prophylactic or on-demand treatment of bleeding in people with hemophilia A or von Willebrand's disease (vWD).[56305] [56306] Factor VIII concentrates are the treatment of choice for hemophilia A.[55323] Plasma-derived von Willebrand factor (vWF)-containing factor VIII concentrates are used in certain types of vWD that do not respond to desmopressin, as well as in surgical situations.[64333] Reduction in vWF results in a correspondingly low factor VIII activity, making replacement of both important in vWD.[64325] Both plasma-derived and recombinant concentrates are suitable for the management of bleeding disorders; screening plasma donors, testing for viral presence, viral inactivation and/or reduction have improved the safety of plasma-derived products. The development of factor replacement products with prolonged half-lives improves patient adherence by enabling less frequent infusions, decreasing the bleeding rate, and reducing the burden of treatment.[62144] Several technologies have been applied to extend the half-life of factor VIII, including the addition of polyethylene glycol (PEG) to factor VIII.[60296] [63486] [63978] The most serious iatrogenic complication of hemophilia treatment is the development of factor inhibitors, which causes neutralization of the infused factor. Inhibitors are more common in hemophilia A, developing in up to 30% of patients. In comparison, the incidence in those with hemophilia B is approximately 5%.[64334] In patients with vWD, an excessive rise in factor VIII activity may increase the risk of thromboembolism. Assess each patient's risk of thrombosis, monitor plasma vWF:RCo and factor VIII activities, and institute appropriate antithrombotic measures in patients receiving coagulation factor replacement therapy as necessary.[64325]

Classifications

Blood and Blood Forming Organs
- Antihemorrhagics
  - Hemostatics
    - Blood Coagulation Factors

Revision Date: 03/07/2024, 05:11:40 PM

References

55323 - Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al. Guidelines for the management of hemophilia. Haemophilia 2013;19:e1-e47.56305 - Wilate (von Willebrand factor/coagulation factor VIII complex, human) package insert. Paramus, NJ: Octapharma USA Inc.; 2024 Nov.56306 - Humate-P (antihemophilic factor/von Willebrand factor complex, human) package insert. Kankakee, IL: CSL Behring LLC; 2017 Sept.60296 - Adynovate (antihemophilic factor [recombinant], PEGylated) package insert. Lexington, MA: Takeda Pharmaceuticals U.S.A., Inc.; 2023 Aug.62144 - Franchini M. Current management of hemophilia B: recommendations, complications and emerging issues. Expert Rev Hematol 2014;7:573-581.63486 - JIVI [antihemophilic factor (recombinant), PEGylated-aucl] package insert. Whippany, NJ: Bayer HealthCare LLC; 2018 Aug.63978 - Esperoct (antihemophilic factor [recombinant], glycopegylated-exei) lyophilized powder for solution package insert. Plainsboro, NJ; Novo Nordisk Inc.: 2024 Feb.64325 - National Heart, Lung, and Blood Institute (NHLBI). Diagnosis, evaluation, and management of von Willebrand disease. NIH Publication No. 08-5832. US Department of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute;2007.64333 - Medical and Scientific Advisory Council (MASAC) of the National Hemophilia Foundation. MASAC recommendations concerning products licensed for the treatment of hemophilia and other bleeding disorders. MASAC document #253. Revised April 2018. Available at: https://www.hemophilia.org/sites/default/files/document/files/masac253.pdf64334 - Zimmerman B, Valentino LA. Hemophilia: in review. Pediatr Rev 2013;34:289-294.

Administration Information

General Administration Information

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

Route-Specific Administration

Injectable Administration

Intravenous Administration

Administer under the direct supervision of a physician experienced in the treatment of hemophilia.
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.[56325]
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 as a bolus infusion over a period of 5 minutes or less (maximum infusion rate 10 mL/minute).[56320] [60296]
Afstyla, Alphanate, Hemofil M: Administer at a rate not to exceed 10 mL/minute.[56307] [60830]
Esperoct: Infuse slowly over approximately 2 minutes.[63978]
Humate-P: Administer at a rate no faster than 4 mL/minute.[56306]
Helixate FS, Kogenate FS: Administer over 1 to 15 minutes; adapt the rate to the individual patient's response.[56321] [56366]
Jivi: Administer over 1 to 15 minutes (Max: 2.5 mL/minute); adapt the rate to the individual patient's response.[63486]
Koate: Administer at a rate not to exceed 10 mL/minute; adapt the rate to the individual patient's response.[61730]
Koate-DVI: Administer over 5 to 10 minutes.[56365]
Kovaltry: Administer over 1 to 15 minutes; adapt the rate to the individual patient's response.[60650]
Monoclate-P: Administer at a rate of approximately 2 mL/minute.[56326]
Novoeight: Administer over 2 to 5 minutes.[56302]
Nuwiq: Administer at a rate no faster than 4 mL/minute; determine rate by the patient's comfort level.[60156]
Recombinate: Administer at a rate up to 5 mL/minute; determine rate by the patient's comfort level.[56325]
Xyntha: Administer over several minutes; determine rate by the patient's comfort level.[56329
Wilate: Administer at a rate of 2 to 4 mL/minute.[56305]

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.[24463]
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 factor VIII (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.[32320] [32321]

Clinical Pharmaceutics Information

From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database

Antihemophilic Factor VIII (recombinant)

pH Range

pH of solution not cited.

ReferencesAnon. Manufacturer's information and labeling. (Package insert).

Sodium Content

Sodium content varies by product: Helixate FS - 0.027 to 0.036 mEq/mL. Kogenate - 0.1 to 0.13 mEq/mL. Kogenate FS - 0.027 to 0.036 mEq/mL Recombinate - 0.18 mEq/mL.

ReferencesAnon. Manufacturer's information and labeling. (Package insert).

Stability

Antihemophilic factor VIII injection in intact containers stored as directed by the manufacturer is stable until the labeled expiration date. Intact containers may be stored up to three months at controlled room temperature up to 25 degree C for Kogenate FS and Refacto and up to 30 degree C for Recombinate. The manufacturers recommend use of the reconstituted solutions within 3 hours of preparation because no antimicrobial preservative is present. The reconstituted solution should not be refrigerated. Parti et al. reported that antihemophilic factor VIII (ADVATE) reconstituted as directed was stable for 24 hours with about 92% activity remaining when stored at controlled room temperature. Fernandez et al. evaluated the stability of antihemophilic factor VIII (recombinant) (ADVATE) diluted in normal saline or dextrose and saline solutions that were exposed to ultraviolet and visible light for 10 hours. The authors reported that the factor VIII was stable under conditions similar to those encountered during continuous infusion. NOTE: Also see Sorption.

ReferencesAnon. Manufacturer's information and labeling. (Package insert).

ReferencesFernandez M, Yu T, Bjornson E, et al. Stability of ADVATE, antihemophilic factor (recombinant) plasma/albumin-free method, during simulated continuous infusion. Blood Coagul Fibrinolysis. 2006; 17`

ReferencesMcEvoy GK (ed). AHFS Drug Information (current edition). Bethesda, MD: American Society of Health-System Pharmacists.

ReferencesParti R, Schoppmann A, Lee H, et al. Stability of lyophilized and reconstituted plasma/albumin-free recombinant human factor VIII (ADVATE rAHF-PFM). Haemophilia. 2005; 5

Light Exposure

The manufacturer of Kogenate FS states that the product should be protected from extreme exposure to light during long-term storage. Parti et al. reported discoloration and loss of approximately 30% concentration of reconstituted antihemophilic factor VIII with exposure for 10 hours to natural daylight at about 25 degree C. Under the same conditions, no such loss occurred in the intact unreconstituted lyophilized dosage form. Fernandez et al. evaluated the stability of antihemophilic factor VIII (recombinant) (ADVATE) diluted in normal saline or dextrose and saline solutions were exposed to ultraviolet and visible light for 10 hours. The authors reported that the factor VIII was stable under conditions similar to those encountered during continuous infusion.

ReferencesAnon. Manufacturer's information and labeling. (Package insert).

ReferencesParti R, Ardosa J, Yang L, et al. In vitro stability of recombinant human factor VIII (Recombinate). Haemophilia. 2000; 6

Filtration

Use the filter needle provided to withdraw the drug from the vial during preparation. Sakazume et al. reported on antihemophilic factor VIII (recombinant) from Bayer at a concentration of 1 unit in sodium chloride 0.9% delivered at 1 mL/minute through a polyvinyl chloride (PVC) administration set with two types of 0.2-micron inline filters. No added loss of drug occurred when using a polysulfone filter, but about 35 to 45% loss to the filters occurred when using polyethersulfone filters.

ReferencesIpema HJ, Tanzi-Samaan MG, Moody ML, et al. Drugs to be used with a filter for preparation and/or administration. Hosp pharm. 2012; 47

ReferencesSakazume S, Sasahara K, Kawada T, et al. The adsorption of recombinant factor VIII (Kogenate) to infusion sets and inline filters. Jpn J Pharm Health Care Sci. 2001; 27

Sorption Leaching

Sorption: Antihemophilic factor VIII (recombinant) may undergo loss due to sorption to some plastic administration equipment. However, the available information is by no means definitive or even consistent. There have been many conflicting studies that are confusing and make a simple resolution on which container materials and delivery equipment to use difficult. McLeod et al. evaluated the stability of antihemophilic factor VIII (recombinant) (Kogenate, Bayer) reconstituted to a concentration of 146 units/mL and diluted to concentrations of 10 and 2 units/mL in 100-mL sodium chloride 0.9% in polyvinyl chloride (PVC) bags (Viaflex, Baxter). After storage at room temperature for 48 hours, Western blot analyses found losses of nearly 60% in the more concentrated solutions of 146 and 10 units/mL and about 98% loss from the 2-units/mL solution. Much of the lost factor VIII was able to be recovered by elution of the empty PVC bags. In contrast, the same solutions packaged in polypropylene plastic syringes (Becton Dickinson) stored for 48 hour at room temperature exhibited no loss of factor VIII. The authors suggested using polypropylene syringes and syringe drivers to administer the drug. Schulman, Gitel et al. evaluated the stability of 15 different antihemophilic factor VIII concentrates stored at 4 to 8, 20 to 23, and 37 degree C for up to four weeks. The samples were packaged in original glass containers and polypropylene tubes but NOT in infusion bags. The authors reported the factor VIII concentrates to be stable refrigerated and at room temperature for several days. Schulman, Varon et al. evaluated the completeness of delivery of reconstituted antihemophilic factor VIII concentrate (Monoclate-P) using minipump infusion systems. The concentration of the factor VIII decreased to below 80% of the initial amount after storage for three days in a CADD-1 pump. Acceptable concentrations were maintained using an Infumed minipump for up to seven days. Hurst et al. reported contradictory information in an evaluation of the stability of reconstituted antihemophilic factor VIII (recombinant) (Kogenate, Bayer) concentrate under refrigeration at 5 degree C and at room temperature of 25 to 30 degree C. They found a 10-fold greater loss of factor VIII from the initial delivered solution with polyethylene administration equipment compared to PVC. However, the concentration soon returned to the initial concentration and remained stable for seven days. DiMichelle et al. evaluated the stability of antihemophilic factor VIII (recombinant) 10 units/mL diluted in PVC bags of sodium chloride 0.9% and delivered through administration lines. An initial loss to 57 to 76% of the initial concentration occurred with a gradual return of concentration after about two hours. Addition of human albumin to the samples did not reduce the loss. This result is at variance with the report of McLeod et al. above who reported substantial losses with no recovery. Sakazume et al. evaluated antihemophilic factor VIII (recombinant) (Kogenate, Bayer) at a concentration of 1 unit/mL in sodium chloride 0.9% delivered at 1 mL/minute through PVC and also polybutadiene plastic administration tubing. Drug losses of 10 to 16% occurred with the PVC tubing, but no loss occurred with the polybutadiene tubing. Fernandez et al. evaluated the delivery of antihemophilic factor VIII (recombinant) (ADVATE) using several delivery devices. The report stated that at least 95% of the factor VIII was delivered over 48 hours when using a multi-therapy 6060 pump system (Baxter) for administration. Similarly, using Medex or Harvard syringe pumps or a CADD pump-1 delivery was 83% or greater over 24 or 48 hours. The authors concluded continuous infusion of antihemophilic factor VIII with these devices was safe and effective. Belgaumi et al. evaluated the stability and delivery of antihemophilic factor VIII (Bioclate) 50, 100, and 250 units/mL with and without heparin and vancomycin delivered by MiniMed 404-SP minipump during simulated administration at temperatures of 21, 37, and 39 degree C over periods up to 28 days. Using a chromagenic assay and Western Blot for purity, the authors reported the concentration, temperature, and the presence or absence of heparin and vancomycin did not affect factor VIII stability. Greater than 75% was delivered in most samples over 3 to 7 days; the 50-unit/mL samples at 21 degree C remained stable for 28 days. (NOTE: 75% is an unusually low concentration to be considered "stable.") The use of plastic syringes for handling antihemophilic factor VIII (recombinant) has been suggested because proteins tend to adhere more to glass syringes than to plastic syringes. However, see McLeod et al. above who reported no loss of antihemophilic factor VIII (recombinant) from solution to polypropylene syringes during storage for 48 hours. Leaching: Polysorbate 80, a surfactant known to leach diethylhexyl phthalate plasticizer from polyvinyl chloride (PVC) infusion solution bags and sets, is a component of the formulation of antihemophilic factor VIII (recombinant). However, the surfactant is present in small quantity and substantial leaching of plasticizer is not likely to occur.

ReferencesAnon. Manufacturer's information and labeling. (Package insert).

ReferencesBelgaumi AF, Patrick CC, Deitcher SR. Stability and sterility of a recombinant factor VIII concentrate prepared for continuous infusion administration. Am J Hematol. 1999; 62

ReferencesDiMichele DM, Lasak ME, Miller CH. In vitro factor VIII recovery during the delivery of ultrapure factor VIII concentrate by continuous infusion. Am J Hematol. 1996; 51

ReferencesHurst D, Zabor S, Malianni D, et al. Evaluation of recombinant factor VIII (Kogenate) stability for continuous infusion using a minipump infusion device. Haemophilia. 1998; 4

ReferencesMcLeod AG, Walker JR, Zheng S, et al. Loss of factor VIII activity during storage in PVC containers due to adsorption. Haemophilia. 2000; 6

ReferencesSakazume S, Sasahara K, Kawada T, et al. The adsorption of recombinant factor VIII (Kogenate) to infusion sets and inline filters. Jpn J Pharm Health Care Sci. 2001; 27

ReferencesSchulman S, Gitel S, Martinowitz U. Stability of factor VIII concentrates after reconstitution. Am J Hematol. 1994; 45

ReferencesSchulman S, Varon D, Keller N, et al. Monoclonal purified FVIII for continuous infusion: stability, microbiological safety and clinical experience. Thromb Haemost. 1994; 72

Other Information

Microbial Contamination: Belgaumi et al. evaluated antihemophilic factor VIII (Bioclate) 50, 100, and 250 units/mL with and without heparin and vancomycin delivered by MiniMed 404-SP minipump during simulated administration at temperatures of 21, 37, and 39 degree C over periods up to 28 days. Inoculation of samples with several common bacteria showed rapid growth over three days. The presence of vancomycin caused a modest suppression of Staphylococcus aureus but not Escherichia coli. The authors noted that bacterial contamination could result in systemic infection.

ReferencesBelgaumi AF, Patrick CC, Deitcher SR. Stability and sterility of a recombinant factor VIII concentrate prepared for continuous infusion administration. Am J Hematol. 1999; 62

Stability Max

Maximum reported stability periods: Intact vials- 3 months at room temperature and until the expiration date under refrigeration. Reconstituted solution- Most products 3 hours. See Stability.

ReferencesAnon. Manufacturer's information and labeling. (Package insert).

ReferencesMcEvoy GK (ed). AHFS Drug Information (current edition). Bethesda, MD: American Society of Health-System Pharmacists.

ReferencesParti R, Schoppmann A, Lee H, et al. Stability of lyophilized and reconstituted plasma/albumin-free recombinant human factor VIII (ADVATE rAHF-PFM). Haemophilia. 2005; 5

References

24463 - Schulman S, Gitel S, Martinowitz U. Stability of factor VIII concentrates after reconstitution. Am J Hematol 1994;45:217-23.32320 - Batorova A, Martinowitz U. Continuous infusion of coagulation factors. Haemophilia 2002;8:170-7.32321 - Hurst D, Zabor S, Malianni D, et al. Evaluation of recombinant factor VIII (Kogenate®) stability for continuous infusion using a minipump infusion device. Haemophilia 1998;4:785-9.56302 - Novoeight (antihemophilic factor [recombinant]) package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2018 Dec.56305 - Wilate (von Willebrand factor/coagulation factor VIII complex, human) package insert. Paramus, NJ: Octapharma USA Inc.; 2024 Nov.56306 - Humate-P (antihemophilic factor/von Willebrand factor complex, human) package insert. Kankakee, IL: CSL Behring LLC; 2017 Sept.56307 - Alphanate (antihemophilic factor/von Willebrand factor complex, human) package insert. Los Angeles, CA: Grifols Biologicals Inc.; 2017 Mar.56320 - Advate (antihemophilic factor [recombinant]) package insert. Lexington, MA: Baxalta US Inc; 2018 Dec.56321 - Helixate FS (antihemophilic factor recombinant) package insert. Tarrytown, NY: Bayer Healthcare LLC; 2013 Jan.56325 - Recombinate (antihemophilic factor [recombinant]) package insert. Westlake Village, CA: Baxalta US Inc.; 2018 Jun.56326 - Monoclate-P (antihemophilic factor [human]) package insert. Kankakee, IL: CSL Behring LLC; 2014 Feb.56365 - Koate-DVI (antihemophilic factor [human]) package insert. Research Triangle Park, NC: Grifols Therapeutics Inc; 2012 Aug.56366 - Kogenate FS (antihemophilic factor [recombinant]) package insert. Tarrytown, NY: Bayer HealthCare LLC; 2016 May.60156 - Nuwiq (antihemophilic factor [recombinant]) package insert. Hoboken, NJ: Octapharma USA, Inc.; 2020 Sept.60296 - Adynovate (antihemophilic factor [recombinant], PEGylated) package insert. Lexington, MA: Takeda Pharmaceuticals U.S.A., Inc.; 2023 Aug.60650 - Kovaltry (antihemophilic factor [recombinant]) package insert. Whippany, NJ: Bayer Healthcare LLC; 2021 Oct.60830 - Afstyla (antihemophilic factor [recombinant], single chain) package insert. Kankakee, Il: CSL Behring LLC; 2023 Jun.61730 - Koate (antihemophilic factor [human]) package insert. Deerfield, IL: Baxter Healthcare Corporation; 2018 Jun.63486 - JIVI [antihemophilic factor (recombinant), PEGylated-aucl] package insert. Whippany, NJ: Bayer HealthCare LLC; 2018 Aug.63978 - Esperoct (antihemophilic factor [recombinant], glycopegylated-exei) lyophilized powder for solution package insert. Plainsboro, NJ; Novo Nordisk Inc.: 2024 Feb.

Adverse Reactions

Mild

abdominal pain
anorexia
arthralgia
asthenia
back pain
chills
cough
dental pain
diarrhea
dizziness
drowsiness
dysgeusia
dyspepsia
epistaxis
fatigue
fever
flushing
headache
hyperhidrosis
infection
injection site reaction
insomnia
malaise
myalgia
nasal congestion
nausea
pallor
paresthesias
pharyngitis
pruritus
rash
rhinitis
rhinorrhea
syncope
tremor
urticaria
vomiting

Moderate

angina
antibody formation
bleeding
chest pain (unspecified)
dyspnea
edema
elevated hepatic enzymes
eosinophilia
erythema
hematoma
hemolysis
hepatitis
hyperbilirubinemia
hypotension
infusion-related reactions
lymphadenopathy
orthostatic hypotension
palpitations
peripheral edema
peripheral vasodilation
phlebitis
sinus tachycardia
thrombocytopenia
thrombocytosis
wheezing

Severe

anaphylactic shock
anaphylactoid reactions
angioedema
bradycardia
bronchospasm
cyanosis
hemolytic anemia
pancreatitis
pulmonary embolism
seizures
thromboembolism
thrombosis

Adverse reactions to antihemophilic factor, AHF, factor VIII are usually related to the injection or are allergic reactions. Infusion-related reactions (0.5%) and/or injection site reaction including pain and inflammation (0.4% to 6.6%), extravasation (2.5%), hematoma (2.5%), device-related problems (4.2%), redness (1.2% to 1.9%), face edema (more than 5%), fever (0.4% or more), chest pain (unspecified)/chest discomfort (1%), feeling hot (0.4%), urticaria (0.5% or more), pruritus (0.3% or more), rash (0.3% or more), erythema (0.4%), chills (0.4% or more), hyperhidrosis (0.5%), and anaphylactoid reactions (0.5%) have been reported in patients receiving antihemophilic factor, AHF, factor VIII. Hypersensitivity has been reported in 0.3% to 6% of patients and includes urticaria, chest tightness, rash, pruritus, and edema. Allergic dermatitis (0.8%), ocular hyperemia (0.8%), and eosinophilia (0.5%) have also been reported and may be related to hypersensitivity. Angioedema, erythema, and anaphylactoid reactions, including anaphylactic shock, have been reported with postmarketing use of antihemophilic factor, AHF, factor VIII.[56302] [56305] [56306] [56307] [56325] [56329] [56332] [60156] [60296] [60650] [60830] [63978]

Rarely, after large doses of antihemophilic factor, AHF, factor VIII acute hemolytic anemia, increased bleeding tendency, or hyperfibrinogenemia have been reported. Certain AHF products (Alphanate, Humate-P, Koate-HP, and Koate-DVI) in large and/or frequent doses in persons with A, B, or AB blood types may result in intravascular hemolysis and hemolytic anemia. Consider the administration of serologically compatible type O red blood cells or the administration of AHF produced from group-specific plasma if occurs.[56306] [56307] Decreased incremental recovery (IR), defined as having at least 2 consecutive observations of low IR values [less than 0.6 (International Units/dL)/(International Units/kg)] after treatment with recombinant glycopegylated AHF, was observed in 17 of 59 subjects (28.8%) without factor VIII inhibition within the first 5 exposure days to recombinant glycopegylated AHF in a clinical trial of previously untreated persons younger than 6 years. Decreased IR was temporary and resolved between 15 and 70 exposure days if recombinant glycopegylated AHF was continued. During the period of decreased IR, 14 of 17 subjects experienced a total of 30 bleeds, of which 23.3% were spontaneous bleeds. Persons with decreased IR may have an increased bleeding risk during the decreased IR period. If bleeding is not controlled with the recommended dose of recombinant glycopegylated AHF and/or the expected factor VIII activity concentrations in the plasma are not attained and factor VIII inhibitors are not detected, consider adjusting the dose or dosing frequency, or discontinuing therapy.[63978]

Mild thrombocytopenia has been reported with the use of porcine antihemophilic factor, AHF, factor VIII. Thrombocytopenia is usually mild and does not appear to affect the patients overall hemostasis. Severity and incidence of platelet effect does not appear to be dose-related and may be due to the presence of porcine von Willebrand factor. Pseudothrombocytopenia (platelet clumping leading to a false low reading) has been reported in a single patient receiving antihemophilic factor/von Willebrand factor complex.[56306] Additionally, lymphadenopathy (0.8%) has been reported during clinical trials of antihemophilic factor, AHF, factor VIII.[60650]

All plasma-derived, human antihemophilic factor, AHF, factor VIII products carry the possibility of causing iatrogenic infection via bloodborne pathogens. The risk of infection associated with plasma-derived AHF products is low due to the careful screening of plasma donors and manufacturing processes, which includes heat-inactivation, solvent detergent viral inactivation process, and monoclonal antibody purification that effectively removes HIV-1, HIV-2, hepatitis B, and hepatitis C. However, new blood-borne pathogens not controlled by present measures can theoretically emerge at any time.[56306] [56332] Transmission of parvovirus B19, hepatitis, and HIV infection through the use of plasma-derived AHF products has been documented. Infectious adverse reactions reported in patients receiving antihemophilic factor, AHF, factor VIII include upper respiratory tract infection (9% to 22%), lower respiratory tract infection (8.4%), ear infection (0.5% to 5%), varicella (4.2%); respiratory tract infections (upper 49% and lower 24%) and varicella (14%) are also common in pediatric patients.[56320] [56325] [60156]

Antibody formation has occurred after administration of antihemophilic factor, AHF, factor VIII. Monitor for the development of factor VIII inhibitors by appropriate clinical observations and laboratory tests. If expected factor VIII activity plasma concentrations are not attained, or if bleeding is not controlled after AHF administration, suspect the presence of an inhibitor (neutralizing antibody).[56302] [56320] [56325] [60650] [63978] Controlling bleeding in persons with hemophilia is more challenging in the presence of inhibitors. For low titer inhibitors, AHF replacement therapy is recommended for the treatment of acute bleeds if measurable factor VIII activity concentrations are achieved. For high titer inhibitors, bypass agent therapy with recombinant factor VIIa, activated prothrombin complex concentrate, or porcine factor VIII is recommended to treat bleeds. Inhibitors are associated with increased risk of musculoskeletal complications, pain, and physical limitations, which may impact physical functioning and quality of life.[68659] Inhibitors in hemophilia are immunoglobulin G (IgG) alloantibodies to exogenous clotting factor VIII that neutralize the function of factor VIII products. The cumulative incidence of inhibitor development in previously untreated persons (PUPs) with hemophilia A is approximately 30%. Inhibitors are more frequently encountered in persons with severe hemophilia than in those with moderate or mild hemophilia and are more common in hemophilia A than hemophilia B. The incidence of inhibitors in mild and moderate hemophilia A is 5% to 10% lower than in those with severe hemophilia A.[68659] In a clinical trial with recombinant AHF, 24 of 56 PUPs (42.9%) developed factor VIII inhibitors with a mean of 14.1 exposure days at the time of first positive inhibitor test; 15 (26.8%) PUPs developed high tighter inhibitors [5 Bethesda Units (BU) or more].[56302] In clinical trials with recombinant glycopegylated AHF, 0.4% of previously treated persons (PTPs) developed factor VIII inhibitors compared to 26.3% of PUPs. Of 70 subjects with at least 10 exposure days to recombinant glycopegylated AHF or previously confirmed factor VIII inhibitors, 30% developed inhibitors; 15.7% developed high tighter inhibitors and 14.3% developed low titer inhibitors. Decreased incremental recovery (IR) may be associated with high titers of anti-polyethylene glycol (PEG) binding antibodies. In PUPs, high titers of anti-PEG IgG antibodies were associated with low factor VIII IR. As treatment with recombinant glycopegylated AHF was continued, titers of anti-PEG IgG decreased and IR returned to 0.6 (International Units/dL)/(International Units/kg) or more between 15 and 70 exposure days to recombinant glycopegylated AHF. Additionally, there have been reports of decreased factor VIII activity in the absence of detectable factor VIII inhibitors in PTPs when switching to recombinant glycopegylated AHF from other factor VIII products.[63978]

The use of factor VIII-containing products in patients with von Willebrand disease (vWD) has been associated with thrombosis and thromboembolism. Monitor factor VIII and vWF:RCo plasma concentrations to avoid sustained excessive vWF and factor VIII activity concentrations (more than 150 International Units/dL). Consider antithrombotic measures in at-risk vWD patients who are receiving coagulation factor replacement therapy.[56305] [56306] [56307] A patient who received a dose of 60 vWF:RCo International Units/kg developed a pulmonary embolism; the FVIII:C concentration achieved in this patient was 290%.[56307] Unexplained transient worsening of preexisting thrombocytosis occurred in 3.6% of patients with hemophilia A receiving vWF-containing factor VIII concentrate for routine prophylaxis during clinical trials.[56305]

Elevated hepatic enzymes (0.5% to 1.4%), hyperbilirubinemia (0.5%), and benign renal neoplasm (0.5%) have been reported in patients receiving antihemophilic factor, AHF, factor VIII.[56302] [60156] Two cases of acute pancreatitis, with no precipitating cause identified in 1 case, were reported during an extension study of a clinical trial that evaluated 216 patients. Administration of antihemophilic factor, AHF, factor VIII continued and both cases resolved.[60296]

Central nervous system (CNS) adverse reactions reported in patients receiving antihemophilic factor, AHF, factor VIII in clinical trials include headache (0.8% to 24%), fatigue (0.5% or more), paresthesias (0.4% or more), dizziness (0.5% to 3.4%), syncope (0.5% to 1.7%), drowsiness (0.9%), insomnia (1.1% to 2.1%), malaise (1.1%), deterioration in neurologic function/behavior (0.5% to 1.7%), tremor (0.5%), head injury (2.6%), and injury (2.6%). Seizures have been reported with postmarketing use. CNS adverse reactions, such as dizziness and paresthesias, have also been reported with postmarketing use of antihemophilic factor, AHF, factor VIII as symptoms of allergic or hypersensitivity reactions.[49402] [56305] [56306] [56307] [56332] [60156] [60296] [60650][60830]

Gastrointestinal (GI) adverse reactions reported in patients receiving antihemophilic factor, AHF, factor VIII in clinical trials include nausea (0.5% to 13%), vomiting (1.5% to 12%), diarrhea (0.4% to 8%), dysgeusia (0.4% to 1.4%), anorexia (0.9%), gastroenteritis (0.5%), abdominal pain (0.5% to 5.3%), abdominal discomfort (1.3%), dyspepsia (1.7%), dental pain/toothache (3.2%), tonsillitis (2.6%), and tooth abscess (2.6%). In pediatric patients 2 to 11 years, abdominal pain (10%) was reported. GI adverse reactions, such as nausea and vomiting, have also been reported with postmarketing use of antihemophilic factor, AHF, factor VIII as symptoms of allergic or hypersensitivity reactions.[49402] [56306] [56320] [56321] [56325] [56332] [60296] [60650]

Musculoskeletal adverse reactions reported in patients receiving antihemophilic factor, AHF, factor VIII in clinical trials include arthralgia (5.3% to 23%), back pain (3.7%), extremity pain (3.7% in adults and 10% in children), joint pain (more than 5%), pain (0.5% or more), asthenia (1.4% to 6%), muscle weakness (0.5%), and myalgia (0.5%).[49402] [56307] [56325] [56329]

Cardiovascular (CV) and vascular adverse reactions reported in patients receiving antihemophilic factor, AHF, factor VIII in clinical trials include orthostatic hypotension (2.6%), peripheral vasodilation (1.4% to 2.3%), thrombo-phlebitis (1.5%), peripheral edema (1.4%), flushing (0.3% to 1%), angina (0.5%), sinus tachycardia (0.5% to 0.8%), hypotension (0.5%), palpitations (0.8%), and pallor (0.5%). Cyanosis, bradycardia, and cardiopulmonary arrest have been reported with postmarketing use. CV adverse reactions, such as tachycardia, chest tightness, hypotension, and flushing, have also been reported with postmarketing use of antihemophilic factor, AHF, factor VIII as symptoms of allergic or hypersensitivity reactions.[56306] [56307] [56321] [56325] [56329] [56332] [60296] [60650]

Respiratory adverse reactions reported in patients receiving antihemophilic factor, AHF, factor VIII in clinical trials include cough (0.5% to 20%), naso-pharyngitis (17%), pharyngitis (5.3%) pharyngolaryngeal pain (0.5% to 9%), nasal congestion (8%), rhinitis (7.9% in adults and 19% in children), rhinorrhea (5%), dyspnea (1.1% to 2.8%), cough (0.5% to 19%), and epistaxis (0.5%). Bronchospasm and hyperventilation have been reported with postmarketing use. Respiratory adverse reactions, such as shortness of breath and wheezing, have also been reported with postmarketing use of antihemophilic factor, AHF, factor VIII as symptoms of allergic or hypersensitivity reactions.[56307] [56321] [56325] [56329] [60156]

Revision Date: 03/07/2024, 05:11:40 PM

References

49402 - Xyntha (antihemophilic factor [recombinant]) package insert. Philadelphia, PA: Wyeth Pharmaceuticals Inc.; 2020 Aug.56302 - Novoeight (antihemophilic factor [recombinant]) package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2018 Dec.56305 - Wilate (von Willebrand factor/coagulation factor VIII complex, human) package insert. Paramus, NJ: Octapharma USA Inc.; 2024 Nov.56306 - Humate-P (antihemophilic factor/von Willebrand factor complex, human) package insert. Kankakee, IL: CSL Behring LLC; 2017 Sept.56307 - Alphanate (antihemophilic factor/von Willebrand factor complex, human) package insert. Los Angeles, CA: Grifols Biologicals Inc.; 2017 Mar.56320 - Advate (antihemophilic factor [recombinant]) package insert. Lexington, MA: Baxalta US Inc; 2018 Dec.56321 - Helixate FS (antihemophilic factor recombinant) package insert. Tarrytown, NY: Bayer Healthcare LLC; 2013 Jan.56325 - Recombinate (antihemophilic factor [recombinant]) package insert. Westlake Village, CA: Baxalta US Inc.; 2018 Jun.56329 - Refacto (antihemophilic factor recombinant) package insert. Cambridge, MA: Genetics Institute, Inc.; 2000 Mar.56332 - Hemofil M (antihemophilic factor [human], method M) package insert. Lexington, MA: Baxalta US Inc.; 2018 Jun.60156 - Nuwiq (antihemophilic factor [recombinant]) package insert. Hoboken, NJ: Octapharma USA, Inc.; 2020 Sept.60296 - Adynovate (antihemophilic factor [recombinant], PEGylated) package insert. Lexington, MA: Takeda Pharmaceuticals U.S.A., Inc.; 2023 Aug.60650 - Kovaltry (antihemophilic factor [recombinant]) package insert. Whippany, NJ: Bayer Healthcare LLC; 2021 Oct.60830 - Afstyla (antihemophilic factor [recombinant], single chain) package insert. Kankakee, Il: CSL Behring LLC; 2023 Jun.63978 - Esperoct (antihemophilic factor [recombinant], glycopegylated-exei) lyophilized powder for solution package insert. Plainsboro, NJ; Novo Nordisk Inc.: 2024 Feb.68659 - Srivastava A, Santagostino E, Dougall A, et al; WFH Guidelines for the Management of Hemophilia panelists and co-authors. WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia. 2020 Aug;26 Suppl 6:1-158.

Contraindications/Precautions

Absolute contraindications are italicized.

bovine protein hypersensitivity
hamster protein hypersensitivity
mannitol hypersensitivity
murine protein hypersensitivity
polysorbate 80 hypersensitivity
anemia
breast-feeding
cardiac disease
factor VIII inhibitors
hepatitis
human immunodeficiency virus (HIV) infection
infection
latex hypersensitivity
pregnancy
thromboembolic disease
viral infection

There are no adequate and well-controlled studies using antihemophilic factor, AHF, factor VIII in pregnancy to determine whether there is a drug-associated risk as hemophilia mainly affects males. Animal reproduction studies have not been conducted.[49402] [56302] [60830] [63978]

There are no data describing the presence of antihemophilic factor, AHF, factor VIII in breast milk, the effect on the breast-fed 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 breast-fed infant from AHF or the mother's underlying condition.[56302] [60830] [63978]

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.

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.

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.

Antihemophilic factor, AHF, factor VIII is contraindicated in patients who have had life-threatening hypersensitivity reactions to any constituents of the product.[56366] 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.[56332] [56326] Recombinate contains trace amounts of bovine, hamster, and mouse proteins.[56325] Helixate FS, Kogenate FS, Advate, Adynovate, and Kovaltry contain trace amounts of hamster and mouse proteins.[56320] [56321] [56329] [56366] [60296] [60650] Afstyla, Novoeight, and Xyntha contain trace amounts of hamster proteins.[49402] [56302] [60830] Esperoct is contraindicated in patients with hamster protein hypersensitivity.[63978] Jivi is contraindicated in patients with hamster protein hypersensitivity, murine protein hypersensitivity, or polyethylene glycol (PEG) hypersensitivity.[63486] Advate, Adynovate, and Monoclate-P contain mannitol and are contraindicated in patients who have a mannitol hypersensitivity.[56320] [56326] [60296] 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.[49402] [56302] [56320] [56325] [56365] [56366] [60296] [60650] [60830] [61389] Use Recombinate with caution in patients with a latex hypersensitivity; certain components used in the packaging contain natural rubber latex.[56325]

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.[25569]

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.[56366]

The formation of factor VIII inhibitors (neutralizing antibodies) may occur after antihemophilic factor, AHF, factor VIII administration. Previously untreated patients are at greatest risk for inhibitor development with all factor VIII products. Monitor all patients for the development of inhibitors by appropriate clinical observation and laboratory tests. Perform testing for factor VIII inhibitors if plasma factor VIII concentrations are not achieved or if bleeding is not controlled by an appropriate dose.[56302] [63978]

Revision Date: 03/07/2024, 05:11:40 PM

References

25569 - de Biasi R, Rocine A, Quirino A, et al. The impact of a very high purity factor VIII concentrate on the immune system of HIV-infected haemophiliacs: a randomized, two-year comparison with a high purity concentrate. Haemophilia 1996;2:82-7.49402 - Xyntha (antihemophilic factor [recombinant]) package insert. Philadelphia, PA: Wyeth Pharmaceuticals Inc.; 2020 Aug.56302 - Novoeight (antihemophilic factor [recombinant]) package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2018 Dec.56320 - Advate (antihemophilic factor [recombinant]) package insert. Lexington, MA: Baxalta US Inc; 2018 Dec.56321 - Helixate FS (antihemophilic factor recombinant) package insert. Tarrytown, NY: Bayer Healthcare LLC; 2013 Jan.56325 - Recombinate (antihemophilic factor [recombinant]) package insert. Westlake Village, CA: Baxalta US Inc.; 2018 Jun.56326 - Monoclate-P (antihemophilic factor [human]) package insert. Kankakee, IL: CSL Behring LLC; 2014 Feb.56329 - Refacto (antihemophilic factor recombinant) package insert. Cambridge, MA: Genetics Institute, Inc.; 2000 Mar.56332 - Hemofil M (antihemophilic factor [human], method M) package insert. Lexington, MA: Baxalta US Inc.; 2018 Jun.56365 - Koate-DVI (antihemophilic factor [human]) package insert. Research Triangle Park, NC: Grifols Therapeutics Inc; 2012 Aug.56366 - Kogenate FS (antihemophilic factor [recombinant]) package insert. Tarrytown, NY: Bayer HealthCare LLC; 2016 May.60296 - Adynovate (antihemophilic factor [recombinant], PEGylated) package insert. Lexington, MA: Takeda Pharmaceuticals U.S.A., Inc.; 2023 Aug.60650 - Kovaltry (antihemophilic factor [recombinant]) package insert. Whippany, NJ: Bayer Healthcare LLC; 2021 Oct.60830 - Afstyla (antihemophilic factor [recombinant], single chain) package insert. Kankakee, Il: CSL Behring LLC; 2023 Jun.61389 - Helixate FS (antihemophilic factor [recombinant]) package insert. Kankakee, IL: CSL Behring LLC; 2016 May.63486 - JIVI [antihemophilic factor (recombinant), PEGylated-aucl] package insert. Whippany, NJ: Bayer HealthCare LLC; 2018 Aug.63978 - Esperoct (antihemophilic factor [recombinant], glycopegylated-exei) lyophilized powder for solution package insert. Plainsboro, NJ; Novo Nordisk Inc.: 2024 Feb.

Mechanism of Action

Factor VIII acts in the coagulation cascade to accelerate the cleavage of factor X by activated factor IX. Factor VIII dramatically increases the maximal velocity of the reaction. Low concentrations of factor VIII (0.2 ng/mL of plasma) are required for normal hemostasis. A severe decrease (more than 80%) or lack of the factor lead to the bleeding disorder known as hemophilia A or classical hemophilia. Factor VIII circulates in a noncovalent complex with von Willebrand factor (vWF). The complex with vWF increases the synthesis of factor VIII, protects factor VIII from proteolysis, and concentrates factor VIII at the site of active bleeding. Factor VIII cannot become part of the "tenase" complex (the calcium-dependent complex of activated factor VIII [factor VIIIa], factor IXa and phospholipid) until it is released from vWF since vWF inhibits the binding of factor VIII to phospholipid. The release of factor VIII from vWF requires cleavage of the factor VIII light chain by thrombin or factor Xa. This results in activation of factor VIII and binding of factor VIIIa to phospholipid surfaces of damaged cells and activated platelets. Factor VIIIa is unstable and rapidly loses its activity. Factor VIIIa undergoes subunit disassociation and is inactivated via proteolytic cleavage by activated protein C.[25742]

The increase in plasma factor VIII activity produced by antihemophilic factor (AHF) may vary by product. In general, 1 International Unit/kg of AHF increases plasma factor VIII activity by approximately 2 International Units/dL.[56302][56332][60156][63978] Additionally, 1 International Unit/kg of Humate-P increases the von Willebrand Factor:Ristocetin Cofactor (vWF:RCo) activity by 5 International Units/dL.[56306]

Revision Date: 03/07/2024, 05:11:40 PM

References

25742 - Hoyer LW. Hemophilia A. N Engl J Med 1994;330:38-47.56302 - Novoeight (antihemophilic factor [recombinant]) package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2018 Dec.56306 - Humate-P (antihemophilic factor/von Willebrand factor complex, human) package insert. Kankakee, IL: CSL Behring LLC; 2017 Sept.56332 - Hemofil M (antihemophilic factor [human], method M) package insert. Lexington, MA: Baxalta US Inc.; 2018 Jun.60156 - Nuwiq (antihemophilic factor [recombinant]) package insert. Hoboken, NJ: Octapharma USA, Inc.; 2020 Sept.63978 - Esperoct (antihemophilic factor [recombinant], glycopegylated-exei) lyophilized powder for solution package insert. Plainsboro, NJ; Novo Nordisk Inc.: 2024 Feb.

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.[56306]

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).[56325][56326][56329] 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.[56320][56326] 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.[56305][56306][56307]

Route-Specific Pharmacokinetics

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.

Special Populations

Pediatrics

During pharmacokinetic trials of recombinant antihemophilic factor (Novoeight), children demonstrated significantly faster clearance than adolescents and adults. The mean clearance was 29% to 60% (clotting assay) and 34% to 67% (chromogenic assay) higher. The mean clearance was 4.6 to 6.26 mL/kg/hour and 3.7 to 5.02 mL/kg/hour in children 0 to 5 years and 6 to 11 years, respectively, compared to a mean clearance of 2.87 to 3.74 mL/kg/hour in adults. The mean half-life was 7.7 to 10 hours and 8 to 9.4 hours in pediatric patients 0 to 5 years and 6 to 11 years, respectively, compared to a mean half-life of 10.8 to 12 hours in adults.[56302] In pharmacokinetic trials of another recombinant antihemophilic factor (Adynovate), children also demonstrated significantly faster clearance than adolescents and adults. The mean clearance was 3.53 mL/kg/hour for children 2 to 5 years and 3.11 mL/kg/hour for children 6 to 11 years, compared with 3.87 mL/kg/hour for adolescents 12 to 17 years and 2.27 mL/kg/hour for adults. Corresponding mean elimination half-lives were 11.8, 12.4, 13.43, and 14.69 hours, respectively.[60296] Similar trends in pharmacokinetic parameters have been observed with other antihemophilic factor products.[56320][56321]

Revision Date: 03/07/2024, 05:11:40 PM

References

56302 - Novoeight (antihemophilic factor [recombinant]) package insert. Plainsboro, NJ: Novo Nordisk Inc.; 2018 Dec.56305 - Wilate (von Willebrand factor/coagulation factor VIII complex, human) package insert. Paramus, NJ: Octapharma USA Inc.; 2024 Nov.56306 - Humate-P (antihemophilic factor/von Willebrand factor complex, human) package insert. Kankakee, IL: CSL Behring LLC; 2017 Sept.56307 - Alphanate (antihemophilic factor/von Willebrand factor complex, human) package insert. Los Angeles, CA: Grifols Biologicals Inc.; 2017 Mar.56320 - Advate (antihemophilic factor [recombinant]) package insert. Lexington, MA: Baxalta US Inc; 2018 Dec.56321 - Helixate FS (antihemophilic factor recombinant) package insert. Tarrytown, NY: Bayer Healthcare LLC; 2013 Jan.56325 - Recombinate (antihemophilic factor [recombinant]) package insert. Westlake Village, CA: Baxalta US Inc.; 2018 Jun.56326 - Monoclate-P (antihemophilic factor [human]) package insert. Kankakee, IL: CSL Behring LLC; 2014 Feb.56329 - Refacto (antihemophilic factor recombinant) package insert. Cambridge, MA: Genetics Institute, Inc.; 2000 Mar.60296 - Adynovate (antihemophilic factor [recombinant], PEGylated) package insert. Lexington, MA: Takeda Pharmaceuticals U.S.A., Inc.; 2023 Aug.

Pregnancy/Breast-feeding

pregnancy

breast-feeding

Revision Date: 03/07/2024, 05:11:40 PM

References

Interactions

There are no drug interactions associated with Antihemophilic Factor, AHF, Factor VIII products.

Revision Date: 03/07/2024, 05:11:40 PM

References

Monitoring Parameters

clotting inhibitor titers
factor VIII concentrations
von Willebrand's factor activity

US Drug Names

Advate
Adynovate
AFSTYLA
Alphanate
Bioclate
ESPEROCT
Helixate
Helixate FS
Hemofil M
Humate-P
Jivi
Koate
Koate-DVI
Kogenate
Kogenate FS
Kogenate FS with Bio-Set
Kogenate FS with Vial Adaptor
Kovaltry
Monarc-M
Monoclate-P
Novoeight
Nuwiq
Recombinate
ReFacto
Wilate vonWillebrand
XYNTHA
XYNTHA Pre-Filled
XYNTHA Solofuse