Usual Adult Dose for Hemophilia A

ADVATE(R), HEXILATE FS(R), JIVI(R), KOGENATE FS(R):
Dose (IU) = Weight (kg) x Desired factor VIII rise (% normal or IU/dL) x 0.5
Expected factor VIII rise (% of normal): 2 x IU administered / weight (kg)

Control of Bleeding Episodes:
Minor bleeding (early hemarthrosis, minor muscle or oral bleeds): 10 to 20 IU/kg intravenously until bleeding is resolved; repeat for evidence of further bleeding

• Factor VIII level required = 20 to 40% of normal

Moderate bleeding (hemorrhage into muscles/oral cavity, hemarthrosis, known trauma): 15 to 30 IU/kg intravenously every 12 to 24 hours until bleeding is resolved.

• Factor VIII level required = 30 to 60% of normal

Major bleeding (gastrointestinal, intracranial, intraabdominal, intrathoracic, central nervous system, retropharyngeal, retroperitoneal, or iliopsoas sheath bleeds, fractures, head trauma):

• Initial dose: 40 to 50 IU/kg intravenously
• Repeat dose: 20 to 25 IU/kg intravenously every 8 to 12 hours until bleeding is resolved.
• Factor VIII level required = 80 to 100% of normal

Surgery:
Minor surgery (including tooth extraction): 15 to 30 IU/kg intravenously every 12 to 24 hours until bleeding is resolved.

• Factor VIII level required = 30 to 60% of normal

Major surgery (e.g. tonsillectomy, inguinal herniotomy, synovectomy, craniotomy, osteosynthesis, trauma, joint replacement):

• Prior to surgery: 50 IU/kg intravenously to achieve 100% factor VIII activity; continue dosing every 6 to 12 hours to keep factor VIII activity in desired range until healing is complete

Routine Prophylaxis: 25 IU/kg three times a week

AFSTYLA(R), HEMOFIL M(R), NOVOEIGHT(R), NUWIQ(R), RECOMBINATE(R), XYNTHA(R):
Dose (IU) = Weight (kg) x Desired factor VIII rise (% normal or IU/dL) x 0.5
Expected factor VIII rise (% of normal): 2 x IU administered / weight (kg)

Control and Prevention of Bleeding Episodes:
Minor bleeding (superficial muscle, soft-tissue, or oral): dose to post-infusion factor VIII level of 20 to 40% every 12 to 24 hours for at least one day, until bleeding is resolved

Moderate to major bleeding (hemorrhage into muscles/oral cavity, hemarthrosis, known trauma): dose to post-infusion factor VIII level of 30 to 60% every 12 to 24 hours for 3 to 4 days or longer until bleeding is resolved.

Life-threatening bleeding (hemorrhage into muscles/oral cavity, hemarthrosis, known trauma): dose to post-infusion factor VIII level of 60 to 100% every 8 to 24 hours until bleeding is resolved.

Surgery:
Minor surgery (including tooth extraction): dose to post-infusion factor VIII level of 30 to 60% every 24 hours, for at least 1 days until healing is achieved.
Major surgery (intracranial, intraabdominal, joint replacement): dose to post-infusion factor VIII level of 80 to 100% every 8 to 24 hours until wound healing, the continue therapy at least 7 more days maintaining factor VIII level of 30 to 60%.

Routine Prophylaxis: 30 to 40 IU/kg every other day

ELOCTATE(R):
Dose (IU) = Weight (kg) x Desired factor VIII rise (% normal or IU/dL) x 0.5
Expected factor VIII rise (% of normal): 2 x IU administered / weight (kg)

Control of Bleeding Episodes:
Minor to moderate bleeding (joint, superficial muscle without neurovascular compromise except iliopsoas, deep laceration, renal, superficial soft tissue, mucous membranes): 20 to 30 IU/kg intravenously every 24 to 48 hours until bleeding is resolved.

• Factor VIII level required = 40 to 60% of normal

Major bleeding (life/limb threatening hemorrhage, iliopsoas and deep muscle with neurovascular injury, retroperitoneal, intracranial, gastrointestinal): 40 to 50 IU/kg intravenously every 12 to 24 hours until bleeding is resolved (approximately 7 to 10 days)

• Factor VIII level required = 80 to 100% of normal

Surgery:
Minor surgery (including tooth extraction): 25 to 40 IU/kg intravenously; repeat every 24 hours if needed for a duration of at least 1 day until healing is achieved.
Major surgery (intracranial, intraabdominal, joint replacement):

• Prior to surgery: 40 to 60 IU/kg intravenously once prior to surgery
• After surgery: 40 to 50 IU/kg intravenously 8 to 24 hours after surgery, then every 24 for until adequate wound healing, then continue at least 7 days while maintaining factor VIII within target range.
• Factor VIII level required prior to and after surgery= 80 to 120% of normal

Routine Prophylaxis:

• Initial dose: 50 IU/kg every 4 days
• Maintenance dose: 25 to 65 IU/kg every 3 to 5 days
• Adjust frequency based on bleeding episodes.

ESPEROCT(R):
Dose (IU) = Weight (kg) x Desired factor VIII rise (% normal or IU/dL) x 0.5

Control of Bleeding Episodes:
Minor bleeding (early hemarthrosis, minor muscle or oral bleeds): 40 IU/kg intravenously; one dose should be sufficient

Moderate bleeding (more extensive hemarthrosis, muscle bleeding, hematoma): 40 IU/kg intravenously; may give one additional dose after 24 hours

Major bleeding (life or limb threatening, gastrointestinal, intracranial, intraabdominal, intrathoracic, fractures): 40 IU/kg intravenously; may repeat approximately every 24 hours

Surgery:
Minor surgery (including tooth extraction): 50 IU/kg intravenously; may repeat after 24 hours if needed
Major surgery (intracranial, intraabdominal, intrathoracic, joint replacement): 50 IU/kg intravenously; may repeat approximately every 24 hours for the first week, then approximately every 48 hours until wound healing has occurred.

Routine Prophylaxis:

• Initial dose: 50 IU/kg every 4 days
• Adjust frequency based on bleeding episodes.

KOATE(R):
Dose (IU) = Weight (kg) x Desired factor VIII rise (% normal or IU/dL) x 0.5

Control and Prevention of Bleeding Episodes:
Minor bleeding (large bruises, significant cuts/scrapes, uncomplicated joint hemorrhage): 15 IU/kg intravenously every 12 hours (twice daily) until hemorrhage stops and healing achieved (1 to 2 days)

• Factor VIII level required = 30% of normal

Moderate bleeding (nose/mouth/gum bleeds, dental extractions, hematuria): 25 IU/kg intravenously every 12 hours (twice daily) until healing achieved (average of 2 to 7 days)

• Factor VIII level required = 50% of normal

Major bleeding (joint hemorrhage, muscle hemorrhage, major trauma, hematuria, intracranial/intraperitoneal bleeding):
Initial dose: 40 to 50 IU/kg intravenously every 12 hours (twice daily)
Maintenance dose: 25 until healing achieved (up to 10 days)

• Intracranial hemorrhage may require prophylaxis for up to 6 months.
• Factor VIII level required = 80 to 100% of normal

Surgery:
Prior to surgery: 40 to 50 IU/kg intravenously once prior to surgery
After surgery: 40 to 50 IU/kg intravenously for 7 to 10 days or until healing achieved

• Factor VIII level required prior to surgery= 80 to 100% of normal
• Factor VIII level required after surgery= 60 to 100% of normal

Comments:

• Base dose and frequency on clinical response.

OBIZUR(R):
Minor to Moderate Bleeding (superficial muscle without neurovascular compromise, joint): 200 units/kg intravenously every 4 to 12 hours

• Adjust frequency based on clinical response and factor VIII levels
• Factor VIII level required = 50 to 100% of normal

Major Bleeding (moderate to severe intramuscular, retroperitoneal, gastrointestinal, intracranial): 200 units/kg intravenously every 4 to 12 hours

• Adjust frequency based on clinical response and factor VIII levels
• Factor VIII level required = 100 to 200% of normal for acute bleeds; 50 to 100% after bleed is controlled

Comments:

• For treatment of bleeding episodes in acquired hemophilia A
• Safety and efficacy have not been established in patients with baseline anti-porcine factor VIII inhibitor titer over 20 BU.
• Not for treatment of congenital hemophilia A or von Willebrand disease
• Base dose, dose frequency, and treatment duration on bleeding severity, factor VIII levels, and clinical condition.

Usual Pediatric Dose for Hemophilia A

ADVATE(R), HEXILATE FS(R), Kogenate FS(R):
Dose (IU) = Weight (kg) x Desired factor VIII rise (% normal or IU/dL) x 0.5
Expected factor VIII rise (% of normal): 2 x IU administered / weight (kg)

Control of Bleeding Episodes:
Minor bleeding (early hemarthrosis, minor muscle or oral bleeds): 10 to 20 IU/kg intravenously until bleeding is resolved; repeat for evidence of further bleeding

• Factor VIII level required = 20 to 40% of normal

Moderate bleeding (hemorrhage into muscles/oral cavity, hemarthrosis, known trauma): 15 to 30 IU/kg intravenously every 12 to 24 hours until bleeding is resolved.

• Factor VIII level required = 30 to 60% of normal

Major bleeding (gastrointestinal, intracranial, intraabdominal, intrathoracic, central nervous system, retropharyngeal, retroperitoneal, or iliopsoas sheath bleeds, fractures, head trauma):

• Initial dose: 40 to 50 IU/kg intravenously
• Repeat dose: 20 to 25 IU/kg intravenously every 8 to 12 hours until bleeding is resolved.
• Factor VIII level required = 80 to 100% of normal

Surgery:
Minor surgery (including tooth extraction): 15 to 30 IU/kg intravenously every 12 to 24 hours until bleeding is resolved.

• Factor VIII level required = 30 to 60% of normal

Major surgery (e.g. tonsillectomy, inguinal herniotomy, synovectomy, craniotomy, osteosynthesis, trauma, joint replacement):

• Prior to surgery: 50 IU/kg intravenously to achieve 100% factor VIII activity; continue dosing every 6 to 12 hours to keep factor VIII activity in desired range until healing is complete

Routine Prophylaxis: 25 IU/kg every other day

AFSTYLA(R), HEMOFIL M(R), NOVOEIGHT(R), NUWIQ(R), RECOMBINATE(R), XYNTHA(R):
Dose (IU) = Weight (kg) x Desired factor VIII rise (% normal or IU/dL) x 0.5
Expected factor VIII rise (% of normal): 2 x IU administered / weight (kg)

Control and Prevention of Bleeding Episodes:
Minor bleeding (superficial muscle, soft-tissue, or oral): dose to post-infusion factor VIII level of 20 to 40% every 12 to 24 hours for at least one day, until bleeding is resolved

Moderate to major bleeding (hemorrhage into muscles/oral cavity, hemarthrosis, known trauma): dose to post-infusion factor VIII level of 30 to 60% every 12 to 24 hours for 3 to 4 days or longer until bleeding is resolved.

Life-threatening bleeding (hemorrhage into muscles/oral cavity, hemarthrosis, known trauma): dose to post-infusion factor VIII level of 60 to 100% every 8 to 24 hours until bleeding is resolved.

Surgery:
Minor surgery (including tooth extraction): dose to post-infusion factor VIII level of 30 to 60% every 24 hours, for at least 1 days until healing is achieved.
Major surgery (intracranial, intraabdominal, joint replacement): dose to post-infusion factor VIII level of 80 to 100% every 8 to 24 hours until wound healing, the continue therapy at least 7 more days maintaining factor VIII level of 30 to 60%.

Routine Prophylaxis:
12 years and older: 30 to 40 IU/kg every other day
Under 12 years: 30 to 50 IU/kg every other day or three times per week

ELOCTATE(R):
Dose (IU) = Weight (kg) x Desired factor VIII rise (% normal or IU/dL) x 0.5
Expected factor VIII rise (% of normal): 2 x IU administered / weight (kg)

Control of Bleeding Episodes:
Minor to moderate bleeding (joint, superficial muscle without neurovascular compromise except iliopsoas, deep laceration, renal, superficial soft tissue, mucous membranes): 20 to 30 IU/kg intravenously every 24 to 48 hours until bleeding is resolved.

• Factor VIII level required = 40 to 60% of normal

Major bleeding (life/limb threatening hemorrhage, iliopsoas and deep muscle with neurovascular injury, retroperitoneal, intracranial, gastrointestinal): 40 to 50 IU/kg intravenously every 12 to 24 hours until bleeding is resolved (approximately 7 to 10 days)

• Under 6 years: Repeat dose every 8 to 24 hours until bleeding is resolved.
• Factor VIII level required = 80 to 100% of normal

Surgery:
Minor surgery (including tooth extraction): 25 to 40 IU/kg intravenously; repeat every 24 hours if needed for a duration of at least 1 day until healing is achieved.
Major surgery (intracranial, intraabdominal, joint replacement):

• Prior to surgery: 40 to 60 IU/kg intravenously once prior to surgery
• After surgery: 40 to 50 IU/kg intravenously 8 to 24 hours after surgery (6 to 24 hours in patients under 6 years), then every 24 for until adequate wound healing, then continue at least 7 days while maintaining factor VIII within target range.
• Factor VIII level required prior to and after surgery= 80 to 120% of normal

Routine Prophylaxis:

• 6 years and older, initial dose: 50 IU/kg every 4 days
• Under 6 years, initial dose: 50 IU/kg twice a week
• Maintenance dose (all ages): 25 to 65 IU/kg every 3 to 5 days
• More frequent or higher doses (up to 80 IU/kg) may be required.
• Adjust frequency based on bleeding episodes.

ESPEROCT(R):
Dose (IU) = Weight (kg) x Desired factor VIII rise (% normal or IU/dL) x 0.5

Control of Bleeding Episodes:
Minor bleeding (early hemarthrosis, minor muscle or oral bleeds):

• 12 years and older: 40 IU/kg intravenously; one dose should be sufficient
• Under 12 years: 65 IU/kg intravenously; one dose should be sufficient

Moderate bleeding (more extensive hemarthrosis, muscle bleeding, hematoma):

• 12 years and older: 40 IU/kg intravenously; may give one additional dose after 24 hours
• Under 12 years: 65 IU/kg intravenously; may give one additional dose after 24 hours

Major bleeding (life or limb threatening, gastrointestinal, intracranial, intraabdominal, intrathoracic, fractures):

• 12 years and older: 40 IU/kg intravenously; may repeat approximately every 24 hours
• Under 12 years: 65 IU/kg intravenously; may repeat approximately every 24 hours

Surgery:
Minor surgery (including tooth extraction): 50 IU/kg intravenously; may repeat after 24 hours if needed
Major surgery (intracranial, intraabdominal, intrathoracic, joint replacement):

• 12 years and older: 50 IU/kg intravenously; may repeat approximately every 24 hours for the first week, then approximately every 48 hours until wound healing has occurred.
• Under 12 years: 65 IU/kg intravenously; may repeat approximately every 24 hours for the first week, then approximately every 48 hours until wound healing has occurred.

Routine Prophylaxis:

• 12 years and older, initial dose: 50 IU/kg every 4 days
• Under 12 years: 65 IU/kg twice a week
• Adjust frequency based on bleeding episodes.

KOATE(R):
Dose (IU) = Weight (kg) x Desired factor VIII rise (% normal or IU/dL) x 0.5

Control and Prevention of Bleeding Episodes:
Minor bleeding (large bruises, significant cuts/scrapes, uncomplicated joint hemorrhage): 15 IU/kg intravenously every 12 hours (twice daily) until hemorrhage stops and healing achieved (1 to 2 days)

• Factor VIII level required = 30% of normal

Moderate bleeding (nose/mouth/gum bleeds, dental extractions, hematuria): 25 IU/kg intravenously every 12 hours (twice daily) until healing achieved (average of 2 to 7 days)

• Factor VIII level required = 50% of normal

Major bleeding (joint hemorrhage, muscle hemorrhage, major trauma, hematuria, intracranial/intraperitoneal bleeding):
Initial dose: 40 to 50 IU/kg intravenously every 12 hours (twice daily)
Maintenance dose: 25 until healing achieved (up to 10 days)

• Intracranial hemorrhage may require prophylaxis for up to 6 months.
• Factor VIII level required = 80 to 100% of normal

Surgery:
Prior to surgery: 40 to 50 IU/kg intravenously once prior to surgery
After surgery: 40 to 50 IU/kg intravenously for 7 to 10 days or until healing achieved

• Factor VIII level required prior to surgery= 80 to 100% of normal
• Factor VIII level required after surgery= 60 to 100% of normal

Comments:

• Base dose and frequency on clinical response.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Precautions

CONTRAINDICATIONS:

• Hypersensitivity to any of the ingredients

Consult WARNINGS section for additional precautions.

Dialysis

Data not available