Drug Class: Miscellaneous coagulation modifiers
Usual Adult Dose for Hemophilia A
ALPHANATE(R):
Minor Hemorrhage (large bruises, significant cuts or scrapes, uncomplicated joint hemorrhage):
15 international units factor VIII (FVIII)/kg IV every 12 hours to achieve FVIII plasma level of 30% of normal, until hemorrhage stops and healing has been achieved (1 to 2 days)
Moderate Hemorrhage (nose, mouth, and gum bleeds; dental extractions; hematuria):
25 international units FVIII/kg IV every 12 hours to achieve FVIII plasma level of 50% of normal, until healing has been achieved (2 to 7 days, on average)
Major Hemorrhage (joint hemorrhage, muscle hemorrhage, major trauma, hematuria, intracranial and intraperitoneal bleeding):
- Initial dose: 40 to 50 international units FVIII/kg IV every 12 hours to achieve FVIII plasma level of 80% to 100% of normal, for at least 3 to 5 days
- Maintenance dose: 25 international units FVIII/kg IV every 12 hours to maintain FVIII plasma level at 80% to 100% of normal, until healing has been achieved for up to 10 days; intracranial hemorrhage may require prophylaxis therapy for up to 6 months
Surgery:
- Pre-surgery: 40 to 50 international units FVIII/kg IV once to achieve FVIII plasma level of 80% to 100% of normal
- Post-surgery: 30 to 50 international units FVIII/kg IV every 12 hours to maintain FVIII plasma level at 60% to 100% of normal, for the next 7 to 10 days or until healing has been achieved
HUMATE-P(R):
Minor Hemorrhage (early joint or muscle bleed or severe epistaxis):
15 international units FVIII/kg IV to achieve FVIII plasma level of approximately 30% of normal; one infusion may be sufficient. If needed, half of the initial dose may be given once or twice a day for 1 to 2 days.
Moderate Hemorrhage (advanced joint or muscle bleed; neck, tongue, or pharyngeal hematoma without airway compromise; tooth extraction; severe abdominal pain):
- Loading dose: 25 international units FVIII/kg IV to achieve FVIII plasma level of approximately 50% of normal
- Maintenance dose: 15 international units FVIII/kg IV every 8 to 12 hours for first 1 to 2 days to maintain FVIII plasma level at 30% of normal, and then the same dose once or twice a day for up to 7 days, or until adequate wound healing.
Life-Threatening Hemorrhage (major surgery; gastrointestinal bleeding; neck, tongue, or pharyngeal hematoma with potential for airway compromise; intracranial, intraabdominal, or intrathoracic bleeding; fractures):
- Initial dose: 40 to 50 international units FVIII/kg IV
- Maintenance dose: 20 to 25 international units FVIII/kg every 8 hours to maintain FVIII plasma level at 80% to 100% of normal for 7 days, then continue the same dose once or twice a day for another 7 days in order to maintain FVIII plasma level at 30% to 50% of normal.
Usual Adult Dose for von Willebrand's Disease
TREATMENT OF BLEEDING EPISODES IN VON WILLEBRAND DISEASE (VWD):
HUMATE-P(R):
Type 1, Mild VWD (baseline von Willebrand factor:ristocetin cofactor activity [VWF:RCo] typically greater than 30%):
Minor hemorrhage (if desmopressin is inappropriate) or major hemorrhage (e.g., severe or refractory epistaxis, gastrointestinal [GI] bleeding, central nervous system [CNS] trauma, traumatic hemorrhage):
- Loading dose: 40 to 60 international units VWF:RCo/kg IV
- Maintenance dose: 40 to 50 international units VWF:RCo/kg IV every 8 to 12 hours for 3 days to keep VWF:RCo trough greater than 50%; then 40 to 50 international units VWF:RCo/kg IV daily for up to 7 days
- Comments: Monitor and maintain factor VIII (FVIII) levels according to hemophilia A guidelines for major bleeds.
Type 1, Moderate or Severe VWD (baseline VWF:RCo typically less than 30%):
Minor hemorrhage (e.g., epistaxis, oral bleeding, menorrhagia): 40 to 50 international units VWF:RCo/kg IV (1 or 2 doses)
Major hemorrhage (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma, hemarthrosis, traumatic hemorrhage):
- Loading dose: 50 to 75 international units VWF:RCo/kg IV
- Maintenance dose: 40 to 60 international units VWF:RCo/kg IV every 8 to 12 hours for 3 days to keep VWF:RCo trough greater than 50%; then 40 to 60 international units VWF:RCo/kg IV daily for up to 7 days
- Comments: Monitor and maintain FVIII levels according to hemophilia A guidelines for major bleeds.
Types 2 (all variants) and 3 VWD:
Minor hemorrhage (clinical indications above): 40 to 50 international units VWF:RCo/kg IV (1 or 2 doses).
Major hemorrhage (clinical indications above):
- Loading dose: 60 to 80 international units VWF:RCo/kg IV
- Maintenance dose: 40 to 60 international units VWF:RCo/kg IV every 8 to 12 hours for 3 days to keep VWF:RCo trough greater than 50%; then 40 to 60 international units VWF:RCo/kg IV daily for up to 7 days
- Comments: Monitor and maintain FVIII levels according to hemophilia A guidelines for major bleeds.
WILATE(R):
Minor Hemorrhage:
Loading dose: 20 to 40 international units VWF:RCo/kg IV
Maintenance dose: 20 to 30 international units VWF:RCo/kg IV every 12 to 24 hours for up to 3 days, keeping VWF:RCo and FVIII troughs greater than 30%
Comments: In VWD type 3 patients, especially those with GI bleeding, higher doses may be required.
Major Hemorrhage:
Loading dose: 40 to 60 international units VWF:RCo/kg IV
Maintenance dose: 20 to 40 international units VWF:RCo/kg IV every 12 to 24 hours for 5 to 7 days, keeping VWF:RCo and FVIII troughs greater than 50%
Comments: In VWD type 3 patients, especially those with GI bleeding, higher doses may be required.
PREVENTION OF EXCESSIVE BLEEDING DURING AND AFTER SURGERY IN VWD:
ALPHANATE(R):
Minor and Major Surgery/Bleeding (except type 3 VWD patients undergoing major surgery):
Preoperative dose: 60 international units VWF:RCo/kg IV
- Minor surgery/bleeding target FVIII coagulant activity (FVIII:C) levels: 40 to 50 international units/dL
- Major surgery/bleeding target FVIII:C levels: 100 international units/dL
Maintenance dose:
- Minor: 40 to 60 international units VWF:RCo/kg IV every 8 to 12 hours as needed to maintain FVIII:C of 40 to 50 international units/dL, for 1 to 3 days
- Major: 40 to 60 international units VWF:RCo/kg IV every 8 to 12 hours as needed to maintain FVIII:C of 100 international units/dL, for at least 3 to 7 days
Comments:
- Monitor peak and trough VWF:RCo and FVIII:C at least daily.
- VWF:RCo and FVIII:C troughs should remain above 50 international units/dL.
- VWF:RCo and FVIII:C should not exceed 150 international units/dL.
HUMATE-P(R):
Emergency Surgery:
Loading dose: 50 to 60 international units VWF:RCo/kg IV to achieve VWF:RCo of 100 international units/dL and FVIII:C of 80 to 100 international units/dL
Comments: Closely monitor trough coagulation factor levels.
Nonemergency Surgery:
Loading dose calculation (to be administered 1 to 2 hours before surgery): (Target peak VWF:RCo - baseline VWF:RCo) x body weight (kg) / in vivo recovery (IVR) = international units VWF:RCo required. If IVR is not available, assume an IVR of 2 international units/dL per international unit/kg of VWF:RCo administered.
IVR calculation:
1. Measure baseline VWF:RCo.
2. Infuse a calculated dose of VWF:RCo at time 0.
3. At time + 30 minutes, measure VWF:RCo. IVR = (VWF:RCo at time + 30 min - VWF:RCo at baseline) / calculated dose (international units/kg).
Loading dose peak targets:
- Minor/oral surgery: VWF:RCo: 50 to 60 international units/dL; FVIII:C: 40 to 50 international units/dL
- Major surgery: VWF:RCo: 100 international units/dL; FVIII:C: 80 to 100 international units/dL
Maintenance dose: Half the initial loading dose IV generally every 8 or 12 hours (patients with shorter half-lives may require every 6 hours); subsequent dosing should be based on VWF:RCo and FVIII levels
- Oral surgery: Minimum duration of treatment: 8 to 12 hours; VWF:RCo target trough: 30 international units/dL or greater up to 3 days following surgery; FVIII:C target trough: Greater than 30 international units/dL after day 3
- Minor surgery: Minimum duration of treatment: 48 hours; VWF:RCo target trough: 30 international units/dL or greater up to 3 days following surgery; FVIII:C target trough: Greater than 30 international units/dL after day 3
- Major surgery: Minimum duration of treatment: 72 hours; VWF:RCo target trough: Greater than 50 international units/dL up to 3 days following surgery and greater than 30 international units/dL after day 3; FVIII:C target trough: Greater than 50 international units/dL up to 3 days following surgery and greater than 30 international units/dL after day 3
Comments:
- Loading dose peak targets may require additional dosing.
- In the absence of pharmacokinetic data, administer every 8 hours.
- Maximum trough levels should not exceed 100 international units/dL.
- Oral surgery is defined as extraction of fewer than 3 teeth, if the teeth are non-molars and have no bony involvement. Extraction of more than 1 impacted wisdom tooth is considered major surgery. Extraction of more than 2 teeth is considered major surgery in all patients.
- Administer at least 1 maintenance dose following oral surgery based on individual pharmacokinetic values. Subsequent therapy with an antifibrinolytic agent is usually administered until adequate healing is achieved.
Usual Pediatric Dose for Hemophilia A
ALPHANATE(R):
Minor Hemorrhage (large bruises, significant cuts or scrapes, uncomplicated joint hemorrhage):
15 international units factor VIII (FVIII)/kg IV every 12 hours to achieve FVIII plasma level of 30% of normal, until hemorrhage stops and healing has been achieved (1 to 2 days)
Moderate Hemorrhage (nose, mouth, and gum bleeds; dental extractions; hematuria):
25 international units FVIII/kg IV every 12 hours to achieve FVIII plasma level of 50% of normal, until healing has been achieved (2 to 7 days, on average)
Major Hemorrhage (joint hemorrhage, muscle hemorrhage, major trauma, hematuria, intracranial and intraperitoneal bleeding):
- Initial dose: 40 to 50 international units FVIII/kg IV every 12 hours to achieve FVIII plasma level of 80% to 100% of normal, for at least 3 to 5 days
- Maintenance dose: 25 international units FVIII/kg IV every 12 hours to maintain FVIII plasma level at 80% to 100% of normal, until healing has been achieved for up to 10 days; intracranial hemorrhage may require prophylaxis therapy for up to 6 months
Surgery:
- Pre-surgery: 40 to 50 international units FVIII/kg IV once to achieve FVIII plasma level of 80% to 100% of normal
- Post-surgery: 30 to 50 international units FVIII/kg IV every 12 hours to maintain FVIII plasma level at 60% to 100% of normal, for the next 7 to 10 days or until healing has been achieved
Usual Pediatric Dose for von Willebrand's Disease
TREATMENT OF BLEEDING EPISODES IN VON WILLEBRAND DISEASE (VWD):
HUMATE-P(R):
Type 1, Mild VWD (baseline von Willebrand factor:ristocetin cofactor activity [VWF:RCo] typically greater than 30%):
Minor hemorrhage (if desmopressin is inappropriate) or major hemorrhage (e.g., severe or refractory epistaxis, gastrointestinal [GI] bleeding, central nervous system [CNS] trauma, traumatic hemorrhage):
- Loading dose: 40 to 60 international units VWF:RCo/kg IV
- Maintenance dose: 40 to 50 international units VWF:RCo/kg IV every 8 to 12 hours for 3 days to keep VWF:RCo trough greater than 50%; then 40 to 50 international units VWF:RCo/kg IV daily for up to 7 days
- Comments: Monitor and maintain factor VIII (FVIII) levels according to hemophilia A guidelines for major bleeds.
Type 1, Moderate or Severe VWD (baseline VWF:RCo typically less than 30%):
Minor hemorrhage (e.g., epistaxis, oral bleeding, menorrhagia): 40 to 50 international units VWF:RCo/kg IV (1 or 2 doses)
Major hemorrhage (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma, hemarthrosis, traumatic hemorrhage):
- Loading dose: 50 to 75 international units VWF:RCo/kg IV
- Maintenance dose: 40 to 60 international units VWF:RCo/kg IV every 8 to 12 hours for 3 days to keep VWF:RCo trough greater than 50%; then 40 to 60 international units VWF:RCo/kg IV daily for up to 7 days
- Comments: Monitor and maintain FVIII levels according to hemophilia A guidelines for major bleeds.
Types 2 (all variants) and 3 VWD:
Minor hemorrhage (clinical indications above): 40 to 50 international units VWF:RCo/kg IV (1 or 2 doses).
Major hemorrhage (clinical indications above):
- Loading dose: 60 to 80 international units VWF:RCo/kg IV
- Maintenance dose: 40 to 60 international units VWF:RCo/kg IV every 8 to 12 hours for 3 days to keep VWF:RCo trough greater than 50%; then 40 to 60 international units VWF:RCo/kg IV daily for up to 7 days
- Comments: Monitor and maintain FVIII levels according to hemophilia A guidelines for major bleeds.
WILATE(R):
Minor Hemorrhage:
Loading dose: 20 to 40 international units VWF:RCo/kg IV
Maintenance dose: 20 to 30 international units VWF:RCo/kg IV every 12 to 24 hours for up to 3 days, keeping VWF:RCo and FVIII troughs greater than 30%
Comments: In VWD type 3 patients, especially those with GI bleeding, higher doses may be required.
Major Hemorrhage:
Loading dose: 40 to 60 international units VWF:RCo/kg IV
Maintenance dose: 20 to 40 international units VWF:RCo/kg IV every 12 to 24 hours for 5 to 7 days, keeping VWF:RCo and FVIII troughs greater than 50%
Comments: In VWD type 3 patients, especially those with GI bleeding, higher doses may be required.
PREVENTION OF EXCESSIVE BLEEDING DURING AND AFTER SURGERY IN VWD:
ALPHANATE(R):
Minor and Major Surgery/Bleeding (except type 3 VWD patients undergoing major surgery):
Preoperative dose: 75 international units VWF:RCo/kg IV
- Minor surgery/bleeding target FVIII coagulant activity (FVIII:C) levels: 40 to 50 international units/dL
- Major surgery/bleeding target FVIII:C levels: 100 international units/dL
Maintenance dose:
- Minor: 50 to 75 international units VWF:RCo/kg IV every 8 to 12 hours as needed to maintain FVIII:C of 40 to 50 international units/dL, for 1 to 3 days
- Major: 50 to 75 international units VWF:RCo/kg IV every 8 to 12 hours as needed to maintain FVIII:C of 100 international units/dL, for at least 3 to 7 days
Comments:
- Monitor peak and trough VWF:RCo and FVIII:C at least daily.
- VWF:RCo and FVIII:C troughs should remain above 50 international units/dL.
- VWF:RCo and FVIII:C should not exceed 150 international units/dL.
HUMATE-P(R):
Emergency Surgery:
Loading dose: 50 to 60 international units VWF:RCo/kg IV to achieve VWF:RCo of 100 international units/dL and FVIII:C of 80 to 100 international units/dL
Comments: Closely monitor trough coagulation factor levels.
Nonemergency Surgery:
Loading dose calculation (to be administered 1 to 2 hours before surgery): (Target peak VWF:RCo - baseline VWF:RCo) x body weight (kg) / in vivo recovery (IVR) = international units VWF:RCo required. If IVR is not available, assume an IVR of 2 international units/dL per international unit/kg of VWF:RCo administered.
IVR calculation:
1. Measure baseline VWF:RCo.
2. Infuse a calculated dose of VWF:RCo at time 0.
3. At time + 30 minutes, measure VWF:RCo. IVR = (VWF:RCo at time + 30 min - VWF:RCo at baseline) / calculated dose (international units/kg).
Loading dose peak targets:
- Minor/oral surgery: VWF:RCo: 50 to 60 international units/dL; FVIII:C: 40 to 50 international units/dL
- Major surgery: VWF:RCo: 100 international units/dL; FVIII:C: 80 to 100 international units/dL
Maintenance dose: Half the initial loading dose IV generally every 8 or 12 hours (patients with shorter half-lives may require every 6 hours); subsequent dosing should be based on VWF:RCo and FVIII levels
- Oral surgery: Minimum duration of treatment: 8 to 12 hours; VWF:RCo target trough: 30 international units/dL or greater up to 3 days following surgery; FVIII:C target trough: Greater than 30 international units/dL after day 3
- Minor surgery: Minimum duration of treatment: 48 hours; VWF:RCo target trough: 30 international units/dL or greater up to 3 days following surgery; FVIII:C target trough: Greater than 30 international units/dL after day 3
- Major surgery: Minimum duration of treatment: 72 hours; VWF:RCo target trough: Greater than 50 international units/dL up to 3 days following surgery and greater than 30 international units/dL after day 3; FVIII:C target trough: Greater than 50 international units/dL up to 3 days following surgery and greater than 30 international units/dL after day 3
Comments:
- Loading dose peak targets may require additional dosing.
- In the absence of pharmacokinetic data, administer every 8 hours.
- Maximum trough levels should not exceed 100 international units/dL.
- Oral surgery is defined as extraction of fewer than 3 teeth, if the teeth are non-molars and have no bony involvement. Extraction of more than 1 impacted wisdom tooth is considered major surgery. Extraction of more than 2 teeth is considered major surgery in all patients.
- Administer at least 1 maintenance dose following oral surgery based on individual pharmacokinetic values. Subsequent therapy with an antifibrinolytic agent is usually administered until adequate healing is achieved.
Renal Dose Adjustments
Data not available
Liver Dose Adjustments
Data not available
Precautions
Safety and efficacy of Humate-P(R) have not been established in hemophilia A patients younger than 18 years.
Consult WARNINGS section for additional precautions.
Dialysis
Data not available
Other Comments
Administration advice: The manufacturer product information should be consulted.
Storage requirements: The manufacturer product information should be consulted.
Reconstitution/preparation techniques: The manufacturer product information should be consulted.
IV compatibility:
- Wilate(R): Do not mix with other medicinal products.
General:
- One international unit of factor VIII (FVIII)/kg will increase the circulating FVIII level by approximately 2 international units/dL.
- Humate-P(R): The ratio between VWF:RCo and FVIII:C activity is approximately 2.4:1.
- Wilate(R): The ratio between VWF:RCo and FVIII:C activity is approximately 1:1.
Monitoring: The manufacturer product information should be consulted.
Patient advice:
- Inform patients of early signs of hypersensitivity (e.g., hives, generalized urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis). If allergic symptoms occur, discontinue this drug immediately and contact the physician.
- Advise patients to contact their physician or treatment center if they experience a lack of clinical response.
- Advise patients to immediately contact their physician or go to the emergency department if a thromboembolic event should occur.
- Inform patients of the risk of transmitting infections with this drug. Advise patients, especially pregnant women and immunocompromised individuals, to immediately report signs or symptoms of infection (e.g., fever, rash, joint pain, sore throat).
