Helixate FS

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Helixate FS

Classes

Blood Coagulation Factors

Administration

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

Injectable Administration Intravenous Administration

Administer under the direct supervision of a physician experienced in the treatment of hemophilia.
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]

Adverse Reactions
Severe

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

Moderate

dyspnea / Early / 1.1-2.8
orthostatic hypotension / Delayed / 2.6-2.6
hematoma / Early / 2.5-2.5
peripheral vasodilation / Rapid / 2.3-2.3
phlebitis / Rapid / 1.5-1.5
elevated hepatic enzymes / Delayed / 1.4-1.4
peripheral edema / Delayed / 1.4-1.4
chest pain (unspecified) / Early / 0.8-0.8
lymphadenopathy / Delayed / 0.8-0.8
palpitations / Early / 0.8-0.8
sinus tachycardia / Rapid / 0.5-0.8
infusion-related reactions / Rapid / 0.5-0.5
eosinophilia / Delayed / 0.5-0.5
hyperbilirubinemia / Delayed / 0.5-0.5
angina / Early / 0.5-0.5
hypotension / Rapid / 0.5-0.5
erythema / Early / 0.4-0.4
edema / Delayed / Incidence not known
bleeding / Early / Incidence not known
hemolysis / Early / Incidence not known
thrombocytopenia / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
thrombocytosis / Delayed / Incidence not known
wheezing / Rapid / Incidence not known

Mild

infection / Delayed / 0.5-49.0
headache / Early / 0.8-24.0
arthralgia / Delayed / 5.3-23.0
rhinitis / Early / 7.9-19.0
cough / Delayed / 0.5-19.0
pharyngitis / Delayed / 5.3-17.0
nausea / Early / 0.5-13.0
vomiting / Early / 1.5-12.0
abdominal pain / Early / 0.5-10.0
diarrhea / Early / 0.4-8.0
nasal congestion / Early / 8.0-8.0
injection site reaction / Rapid / 0.4-6.6
asthenia / Delayed / 1.4-6.0
rhinorrhea / Early / 5.0-5.0
back pain / Delayed / 3.7-3.7
dizziness / Early / 0.5-3.4
dental pain / Delayed / 3.2-3.2
insomnia / Early / 1.1-2.1
syncope / Early / 0.5-1.7
dyspepsia / Early / 1.7-1.7
dysgeusia / Early / 0.4-1.4
malaise / Early / 1.1-1.1
flushing / Rapid / 0.3-1.0
drowsiness / Early / 0.9-0.9
anorexia / Delayed / 0.9-0.9
hyperhidrosis / Delayed / 0.5-0.5
tremor / Early / 0.5-0.5
myalgia / Early / 0.5-0.5
pallor / Early / 0.5-0.5
chills / Rapid / 0.4
fever / Early / 0.4
rash / Early / 0.3
urticaria / Rapid / 0.5
pruritus / Rapid / 0.3
paresthesias / Delayed / 0.4
fatigue / Early / 0.5
epistaxis / Delayed / Incidence not known

Common Brand Names

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

Dea Class

Rx

Description

Parenteral coagulation factor
Used for perioperative management and on-demand treatment of bleeding in patients with von Willebrand's disease (vWD) and for perioperative management and prophylactic or on-demand treatment of bleeding in patients with hemophilia A
Associated with thromboembolism risk in vWD patients and high rate of inhibitor development in hemophilia A patients

Dosage And Indications
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

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]

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.

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.

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.

Infants, 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 dose every 12 to 24 hours until bleeding episode, as indicated by pain, is resolved or healing achieved.

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

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 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

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]

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

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.

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.

Children and Adolescents 12 to 17 years

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.

Intravenous dosage (Koate) Adults

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

Children and Adolescents

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

Intravenous dosage (Koate-DVI) Adults

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.

Infants, 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 for at least 1 day, until bleeding episode as indicated by pain is resolved, or healing is achieved.

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.

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 every 12 to 24 hours for at least 1 day and until bleeding is resolved.

Intravenous dosage (Nuwiq) Adults

10 to 20 International Units/kg/dose IV to achieve a peak 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 the bleeding episode is resolved.

Children and Adolescents 2 to 17 years

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 the bleeding episode is resolved.

Intravenous dosage (Recombinate) 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.

Infants, Children, and Adolescents

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.

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

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]

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.

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 every 12 to 24 hours until resolved and for at least 1 day depending on the severity of the bleeding episode.

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

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]

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.

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.

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.

Infants, 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 for 3 to 4 days or more until pain and acute disability resolved.

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

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 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

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.

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

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.

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.

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.

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.

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.

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

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.

Intravenous dosage (Kovaltry) 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 are resolved.

Infants, 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 for 3 to 4 days or more until pain and acute disability are resolved.

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.

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 every 12 to 24 hours for approximately 3 to 4 days or until pain and acute disability are resolved.

Intravenous dosage (Nuwiq) Adults

15 to 30 International Units/kg/dose IV to achieve a peak 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.

Children and Adolescents 2 to 17 years

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.

Intravenous dosage (Recombinate) 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.[56325]

Infants, Children, and Adolescents

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.[56325]

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

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]

Intravenous dosage (Xyntha) 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 local hemostasis is achieved.

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 every 12 to 24 hours for 3 to 4 days or until local hemostasis is achieved.

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

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]

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.

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.

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.

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.

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

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 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

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.

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

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]

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

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.

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

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]

Intravenous dosage (Koate) Adults

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

Children and Adolescents

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

Intravenous dosage (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.

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.

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).

Infants, Children, and Adolescents

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).

Intravenous dosage (Nuwiq) 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.

Children and Adolescents 2 to 17 years

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.

Intravenous dosage (Recombinate) 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.

Infants, Children, and Adolescents

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.

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

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]

Intravenous dosage (Xyntha) 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.

Infants, Children, and Adolescents

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.

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. A higher rate of infusion of 4 to 5 International Units/kg/hour has also been suggested.

Infants, Children, and Adolescents

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. A higher rate of infusion of 4 to 5 International Units/kg/hour has also been suggested.

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

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

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.

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

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]

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

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 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.

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 activi

ty concentration of 30% to 60% of normal for another 7 days.

Infants, Children, and Adolescents

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.

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

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.

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

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 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

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.

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

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.

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

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.

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).

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).

Intravenous dosage (Koate) Adults

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

Children and Adolescents

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

Intravenous dosage (Koate-DVI) Adults

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

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.

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.

Infants, Children, and Adolescents

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

Infants, Children, and Adolescents

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.

Intravenous dosage (Adynovate) Adults

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

Children and Adolescents 12 to 17 years

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

Children 1 to 11 years

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

Intravenous dosage (Afstyla) Adults

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

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.

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.

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.

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).

Children and Adolescents 12 to 17 years

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).

Intravenous dosage (Kogenate FS) Adults

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

Infants, Children, and Adolescents

25 International Units/kg/dose IV every other day.

Intravenous dosage (Kovaltry) Adults

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

Adolescents

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

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.

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.

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.

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.

Intravenous dosage (Nuwiq) Adults

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

Children and Adolescents 12 to 17 years

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

Children 2 to 11 years

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

Intravenous dosage (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.

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 orphan drugs for this indication.
For major hemorrhage in patients with mild vWD type I (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma or traumatic hemorrhage). Intravenous dosage (Humate-P) Adults, Adolescents, Children, and Infants

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Adults

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

Infants, Children, and Adolescents

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

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

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

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

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

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

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

Dosing Considerations
Hepatic Impairment

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

Renal Impairment

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

Drug Interactions

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

How Supplied

Advate/Adynovate/AFSTYLA/Alphanate/Antihemophilic Factor (Pooled Human Plasma)/Antihemophilic Factor/von Willebrand Factor Complex (Pooled Human Plasma), Pasterized/Helixate FS/Hemofil M/Humate-P/Jivi/Koate/Koate-DVI/Kogenate FS with Vial Adaptor/Kovaltry/Monoclate-P/Novoeight/Nuwiq/Recombinate/Simoctocog alfa/Wilate vonWillebrand/XYNTHA/XYNTHA Solofuse Intravenous Inj Pwd F/Sol: 1mL, 62.5IU, 125IU, 250IU, 375IU, 500IU, 750IU
Antihemophilic Factor (Recombinant), Glycopegylated/ESPEROCT Intravenous Inj Pwd
Nuwiq Intravenous Pwd

Maximum Dosage

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

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. [63978] Additionally, 1 International Unit/kg of Humate-P increases the von Willebrand Factor:Ristocetin Cofactor (vWF:RCo) activity by 5 International Units/dL.

Pharmacokinetics

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

Intravenous Route

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

Pregnancy And Lactation
Pregnancy

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]