Antihemophilic factor human

Name: Antihemophilic factor human

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Human antihemophilic factor side effects

Get emergency medical help if you have signs of an allergic reaction: hives; chest tightness, wheezing, difficult breathing; feeling light-headed, fainting; swelling of your face, lips, tongue, or throat.

Stop using human antihemophilic factor and call your doctor at once if you have:

  • tingly feeling in your face, ears, or arms;

  • headache, blurred vision, feeling jittery;

  • fever, chills, drowsiness, and runny nose followed by skin rash and joint pain 2 weeks later; or

  • nausea, vomiting, upper stomach pain, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common side effects may include:

  • swelling, stinging, or irritation where the injection was given;

  • chills;

  • mild nausea; or

  • allergic reaction.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Antihemophilic Factor (Human) Dosage and Administration

General

  • Individualize dosage and duration of therapy based on severity of factor VIII or von Willebrand factor deficiency, location and extent of bleeding, and patient's clinical and pharmacokinetic (e.g., in vivo recovery, half-life) response.122 133 158 167 215

  • Monitor factor VIII or von Willebrand factor: Ristocetin cofactor (vWF:RCo) levels periodically during treatment to individualize dosage and assess response to therapy.122 133 153 158 167 Careful control is especially important in cases of life-threatening bleeding or major surgery.122 153 (See Laboratory Monitoring under Cautions.)

Administration

IV Administration

Administer by slow IV injection or by IV infusion over several minutes.122 133 153 158 167

Has been given as a continuous IV infusion†.228 229 230

Reconstitute and administer using plastic syringes only.122 133 153 167

Instructions on reconstitution, dilution, and administration vary according to preparation; consult manufacturer’s labeling for specific information on each antihemophilic factor (human) or antihemophilic factor/von Willebrand factor complex (human) product.122 133 153 158 167

Reconstitution

Prior to reconstitution, allow lyophilized drug and diluent to warm to room temperature; do not exceed 37°C.122 133 153 158 167

Reconstitute using diluent provided by manufacturer.122 133 153 158 167

Following addition of diluent, gently swirl solution to dissolve powder completely; do not shake.122 133 153 167

Rate of Administration

Individualize infusion rates according to patient response.122 158 167 Monitor pulse before and during infusion.153 Slow infusion rate or temporarily discontinue therapy if there is a substantial increase in pulse rate.153

Alphanate, Hemofil-M: Administer at a rate ≤10 mL/minute.122 153

Humate-P: Administer at a rate ≤4 mL/minute.133

Koate-DVI: Generally well-tolerated when given over 5–10 minutes.158

Monoclate-P: Administer at a rate of approximately 2 mL/minute.167

Dosage

Dosage (potency) expressed in terms of international units (IU, units).122 133 153 158 167 One unit is approximately equivalent to amount of factor VIII or vWF:RCo in 1 mL of fresh pooled human plasma.122 133 158 167

Administration of 1 unit/kg antihemophilic factor (human) generally increases factor VIII level by approximately 2% and vWF:Co by approximately 5%.133 154 160 167 176 194 215

Use following formulas to calculate dose or expected increase in factor VIII levels from a given dose in patients with hemophilia A:

Dose required to achieve desired factor VIII levels:122 153 158 167

Dose (units) = body weight (in kg) × 0.5 × desired factor VIII increase (in % of normal)

Approximate % increase in factor VIII levels expected from a given dose:122 153 158 167

Expected factor VIII increase (in % of normal) = [dose (units)/body weight (in kg)] × 2

Determine desired factor VIII level by the clinical situation and severity of bleeding.122 133 153 158 167 (For recommendations on target factor VIII levels, see the individual preparation-specific dosage sections below.) These calculations and suggested dosage regimens are only approximations and should not preclude appropriate clinical monitoring and laboratory determinations of factor VIII levels.122 133 153 158 167 Perform serial assays of factor VIII at suitable intervals to ensure that adequate levels have been attained and maintained.122 133 153 158 167

If calculated dosage is ineffective in achieving adequate factor VIII levels or if bleeding is not controlled, consider possibility of inhibitor development.122 153 215 (See Neutralizing Antibodies to Factor VIII under Cautions.) Some patients with inhibitors may require higher or more frequent doses.122 153 158

Consult manufacturers’ prescribing information for specific dosage recommendations for each antihemophilic factor (human) preparation.122 133 153 158 167

Pediatric Patients

Prevention and Control of Bleeding Episodes in Hemophilia A Alphanate IV

Pediatric patients >16 years of age with minor bleeding (e.g., large bruises, substantial cuts or scrapes, uncomplicated joint bleeding): 15 units/kg twice daily to achieve a plasma factor VIII level of 30% of normal; usually for 1–2 days (until bleeding stops and healing achieved).122

Pediatric patients >16 years of age with moderate bleeding (e.g., epistaxis, mouth and gum bleeding, tooth extraction, hematuria): 25 units/kg twice daily to achieve a plasma factor VIII level of 50% of normal; usually for 2–7 days (until healing achieved).122

Pediatric patients >16 years of age with major bleeding (e.g., joint or muscle bleeding, major trauma, hematuria, intracranial or intraperitoneal hemorrhage): Initially, 40–50 units/kg twice daily to achieve a plasma factor VIII level of 80–100% of normal for at least 3–5 days; give additional doses of 25 units/kg twice daily for up to 10 days (until healing is achieved) to maintain a plasma factor VIII level of 50% of normal.122 Intracranial hemorrhage may require treatment for up to 6 months.122

Pediatric patients >16 years of age undergoing surgery: Initially, 40–50 units/kg to achieve a plasma factor VIII level of 80–100% of normal prior to surgery.122 Give additional doses of 30–50 units/kg twice daily for 7–10 days (or until healing achieved) to maintain a plasma factor VIII level of 60–100% of normal.122

Hemofil-M IV

Early hemarthrosis, muscle bleeding or oral bleeding: Administer appropriate dose to achieve a peak plasma factor VIII postinfusion level of 20–40% of normal.153 To maintain adequate levels, administer doses every 12–24 hours for 1–3 days until bleeding resolves (indicated by relief of pain) or healing achieved.153

More extensive hemarthrosis, muscle bleeding, or hematoma: Administer appropriate dose to achieve peak plasma factor VIII postinfusion level of 30–60% of normal.153 Give doses every 12–24 hours for 3 days or longer until pain and disability resolve.153

Life-threatening bleeding (e.g., head injury, throat bleeding, severe abdominal pain): Administer appropriate dose to achieve a peak plasma factor VIII postinfusion level of 60–100% of normal.153 Give doses every 8–24 hours until bleeding resolves.153

Minor surgery (e.g., tooth extraction): Administer appropriate dose to achieve a peak plasma factor VIII postinfusion level of 60–80% of normal.153 A single infusion given in conjunction with an oral antifibrinolytic agent usually is sufficient in about 70% of patients.153

Major surgery: Administer appropriate dose to achieve peak plasma factor VIII pre- and postoperative levels of 80–100% of normal.153 Repeat doses every 8–24 hours depending on state of healing.153

Monoclate-P IV

Mild bleeding: A single infusion may be sufficient to achieve a plasma factor VIII level of ≥30% of normal.167

Moderate bleeding: Initially, 15–25 units/kg to achieve a plasma factor VIII level of 30–50% of normal.167 If needed, give additional doses of 10–15 units/kg every 8–12 hours.167

Severe bleeding (e.g., neck, throat, subperitoneal bleeding): Initially, 40–50 units/kg and a maintenance dosage of 20–25 units/kg given every 8–12 hours to achieve a plasma factor VIII level of 80–100% of normal.167

Minor surgery: Initially, 15–25 units/kg to achieve a plasma factor VIII level of 30–50% of normal.167 If needed, give additional doses of 10–15 units/kg every 8–12 hours.167

Major surgery: Administer an appropriate dose to achieve a plasma factor VIII level of 80–100% of normal 1 hour before surgery; administer a second dose equal to 50% of the initial dose 5 hours later.167 Maintain a plasma factor VIII level of ≥30% of normal for 10–14 days after surgery.167

Routine Prophylaxis of Bleeding Episodes in Hemophilia A IV

Various dosing regimens have been recommended.215 218 225 231 MASAC states that an antihemophilic factor dosage of 25–50 units/kg 3 times a week or every other day usually is sufficient to maintain trough factor VIII concentrations >1% between infusions.218

MASAC states that prophylaxis should be instituted at an early age (e.g., 1–2 years) prior to the onset of frequent bleeding; however, optimum duration of prophylaxis not known.218

Individualize prophylactic regimens; evaluate patients periodically to determine continued need for prophylaxis.218

von Willebrand Disease (Alphanate)

Amount of vWF:RCo and factor VIII contained in each vial of Alphanate is indicated on the label.122 Ratio of vWF:RCo to factor VIII varies depending on the manufacturing lot; therefore, reevaluate dosage of Alphanate for management of von Willebrand disease whenever a different manufacturing lot is indicated on the vial.122

IV

Patients undergoing a minor surgical or invasive procedure: Initially, 75 units/kg of vWF:RCo prior to procedure to achieve factor VIII levels of 40–50%; follow with additional doses of 50–75 units/kg of vWF:RCo every 8–12 hours as clinically needed for 1–3 days to maintain factor VIII levels at 40–50%.122

Type 1 or type 2 patients undergoing a major surgical or invasive procedure: Initially, 75 units/kg of vWF:RCo prior to procedure to achieve factor VIII levels of 100%; follow with additional doses of 50–75 units/kg of vWF:RCo every 8–12 hours as clinically needed for at least 3–7 days to maintain factor VIII levels at 100%.122

Therapeutic goal is to achieve trough factor VIII and vWF:RCo levels >50%; do not exceed 150%.122

von Willebrand Disease (Humate-P) IV

Adjust dosage according to extent and location of bleeding.133 Usually administer doses of 40–80 units/kg of vWF:RCo (corresponding to 17–33 units/kg of antihemophilic factor) every 8–12 hours; repeat doses for as long as needed based on repeated monitoring of appropriate clinical and laboratory measures.133

Expected levels of vWF:RCo based on expected in vivo recovery of 2% increase per unit/kg of vWF:RCo administered.133 Administration of 1 unit/kg of antihemophilic factor can be expected to result in an increase in circulating vWF:RCo of approximately 5%.133

In all patients with major bleeding, monitor and maintain factor VIII levels according to the usual guidelines for patients with hemophilia A.133

Type 1 (Mild) von Willebrand Disease (Baseline vWF:RCo Activity Typically >30%) IV

Pediatric patients (excluding neonates) with major bleeding (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma, traumatic bleeding) or minor bleeding when use of desmopressin is inadequate or contraindicated: Initially, 40–60 units/kg of vWF:RCo, followed by 40–50 units/kg of vWF:RCo every 8–12 hours for 3 days to maintain a trough vWF:RCo level of >50%.133 Continue with 40–50 units/kg vWF:RCo daily for up to 7 days.133

Type 1 (Moderate or Severe) von Willebrand Disease (Baseline vWF:RCo Activity Typically <30%) IV

Pediatric patients (excluding neonates) with minor bleeding (e.g., epistaxis, oral bleeding, menorrhagia): 40–50 units/kg of vWF:RCo given as 1 or 2 doses.133

Pediatric patients (excluding neonates) with major bleeding (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma, hemarthrosis, traumatic bleeding): Initially, 50–75 units/kg of vWF:RCo, followed by 40–60 units/kg of vWF:RCo every 8–12 hours for 3 days to maintain a vWF:RCo trough level of >50%.133 Continue with 40–60 units/kg of vWF:RCo daily for up to 7 days.133

Type 2 (All Variants) and Type 3 von Willebrand Disease IV

Pediatric patients (excluding neonates) with minor bleeding (e.g., epistaxis, oral bleeding, menorrhagia): 40–50 units/kg of vWF:RCo given as 1 or 2 doses.133

Pediatric patients (excluding neonates) with major bleeding (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma, hemarthrosis, traumatic bleeding): Initially, 60–80 units/kg of vWF:RCo, followed by 40–60 units/kg of vWF:RCo every 8–12 hours for 3 days to maintain a vWF:RCo trough level >50%.133 Continue with 40–60 units/kg of vWF:RCo daily for up to 7 days.133

Prevention of Excessive Perioperative Bleeding in von Willebrand Disease

Whenever possible, calculate dosages for surgical prophylaxis based on incremental in vivo recovery (IVR) values.133 If individual IVR values not available, assume IVR of 2% per unit/kg of vWF:RCo.133 In case of emergency surgery, administer a loading dose of 50–60 units/kg of vWF:RCo and closely monitor trough coagulation factor levels.133

To calculate IVR, use the following formula.133 Measure plasma vWF:RCo level at baseline and 30 minutes following a calculated dose.133

IVR = (plasma vWF:RCotime + 30 minutes - plasma vWF:RCobaseline) / calculated dose (in units/kg)

Calculate loading dose (administered 1–2 hours prior to surgery) using the following formula:133

Dose required (units of vWF:RCo) = [(target peak plasma vWF:RCo - baseline plasma vWF:RCo) x body weight (in kg)]/IVR

Administer loading doses to achieve specific target peak vWF:RCo and factor VIII levels.133 Additional doses may be necessary to achieve recommended factor VIII levels; because of a higher ratio of vWF:RCo to factor VIII (2.4 to 1), vWF:RCo will increase proportionally more than factor VIII with increasing doses.133

Administer initial maintenance dose equal to one-half the loading dose (irrespective of any additional loading doses given to meet target factor VIII goals); follow with additional maintenance doses based on trough plasma vWF:RCo and factor VIII levels.133 Frequency of administration depends on individual pharmacokinetic parameters; in the absence of such data, administer every 8 hours initially.133

Monitor trough vWF:RCo and factor VIII levels at least once daily, and during and after surgery.133 Modify dose and/or frequency of antihemophilic factor administration if hemostasis is insufficient or measured trough coagulation factor levels are not within recommended range.133 Because factor VIII is the main predictor of surgical hemostasis, some clinicians recommend monitoring factor VIII levels every 12 hours on the day a dose is administered, then every 24 hours thereafter.244 Determine duration of therapy based on hemostatic response.133

IV

Pediatric patients (excluding neonates) undergoing major surgery: Administer appropriate loading dose to achieve a target peak plasma vWF:RCo level of 100% and a peak plasma factor VIII level of 80–100%.133 Give initial maintenance dose equal to one-half the loading dose and subsequent doses to achieve target trough vWF:RCo levels of >50% (>50% of factor VIII activity) for up to 3 days following surgery and target trough vWF:RCo levels of >30% (>30% of factor VIII activity) after day 3.133 Minimum duration of treatment is 72 hours.133

Pediatric patients (excluding neonates) undergoing minor surgery: Administer appropriate loading dose to achieve a target peak plasma vWF:RCo level of 50–60% and a peak plasma factor VIII level of 40–50%.133 Give initial maintenance dose equal to one-half the loading dose and subsequent doses to achieve target trough plasma vWF:RCo levels of ≥30% for up to 3 days following surgery and target trough factor VIII levels >30% after day 3.133 Minimum duration of treatment is 48 hours.133

Pediatric patients (excluding neonates) undergoing oral surgery: Administer appropriate loading dose to achieve a target peak vWF:RCo level of 50–60% and a peak plasma factor VIII level of 40–50%.133 Give initial maintenance dose equal to one-half the loading dose and subsequent doses to achieve target trough vWF:RCo levels of ≥30% for up to 3 days following surgery and target trough factor VIII levels >30% after day 3.133 Minimum duration of treatment is 8–12 hours.133

Adults

Prevention and Control of Bleeding Episodes in Hemophilia A Alphanate IV

Minor bleeding (e.g., large bruises, cuts or scrapes, uncomplicated joint bleeding): 15 units/kg twice daily to achieve a plasma factor VIII level of 30% of normal; usually for 1–2 days (until bleeding stops and healing achieved).122

Moderate bleeding (e.g., epistaxis, mouth and gum bleeding, tooth extraction, hematuria): 25 units/kg twice daily to achieve a plasma factor VIII level of 50% of normal; usually for 2–7 days, until healing achieved.122

Major bleeding (e.g., joint or muscle bleeding, major trauma, hematuria, intracranial and intraperitoneal bleeding): Initially, 40–50 units/kg twice daily to achieve a plasma factor VIII level of 80–100% of normal for at least 3–5 days.122 Give additional doses of 25 units/kg twice daily for up to 10 days (until healing is achieved) to maintain a plasma factor VIII level of 50% of normal.122 Intracranial hemorrhage may require treatment for up to 6 months.122

Surgery: Initially, 40–50 units/kg to achieve a plasma factor VIII level of 80–100% of normal prior to surgery.122 Give additional doses of 25–50 units/kg twice daily for 7–10 days (or until healing achieved) to maintain a plasma factor VIII level of 60–100% of normal.122

Humate-P IV

Minor bleeding (e.g., early joint or muscle bleeding, severe epistaxis): Initially, 15 units/kg to achieve a plasma factor VIII level of approximately 30% of normal.133 A single dose may be sufficient; if necessary, administer additional doses equal to 50% of the loading dose once or twice daily for 1–2 days.133

Moderate bleeding (e.g., advanced joint or muscle bleeding; neck, tongue, or pharyngeal hematoma without airway compromise; severe abdominal pain; tooth extraction): Initially, 25 units/kg to achieve a plasma factor VIII level of approximately 50% of normal,133 followed by 15 units/kg every 8–12 hours for the first 1–2 days to maintain a plasma factor VIII level of 30% of normal.133 Thereafter, the same dose may be given once or twice daily for up to 7 days or until adequate wound healing.133

Life-threatening bleeding (e.g., major surgery, GI bleeding; neck, tongue, or pharyngeal hematoma with potential for airway compromise; intracranial, intra-abdominal, or intrathoracic bleeding; fractures): Initially, 40–50 units/kg followed by 20–25 units/kg every 8 hours to maintain a plasma factor VIII level of 80–100% of normal for 7 days.133 Thereafter, the same dose may be given once or twice daily for another 7 days to maintain a plasma factor VIII level of 30–50% of normal.133

Hemofil-M IV

Early hemarthrosis, muscle bleeding or oral bleeding: Administer appropriate dosage to achieve a peak plasma factor VIII postinfusion level of 20–40% of normal.153 To maintain adequate levels, administer doses every 12–24 hours for 1–3 days until bleeding resolves (indicated by relief of pain) or healing achieved.153

More extensive hemarthrosis, muscle bleeding, or hematoma: Administer appropriate dose to achieve peak plasma factor VIII postinfusion level of 30–60% of normal.153 Give doses every 12–24 hours for 3 days or longer until pain and disability resolve.153

Life-threatening bleeding (e.g., head injury, throat bleeding, severe abdominal pain): Administer appropriate dose to achieve a peak plasma factor VIII postinfusion level of 60–100% of normal.153 Give doses every 8–24 hours until bleeding resolves.153

Minor surgery (e.g., tooth extraction): Administer appropriate dose to achieve a peak plasma factor VIII postinfusion level of 60–80% of normal.153 A single infusion given in conjunction with an oral antifibrinolytic agent usually is sufficient in about 70% of patients.153

Major surgery: Administer appropriate dose to achieve peak plasma factor VIII pre- and postoperative levels of 80–100% of normal.153 Repeat doses every 8–24 hours depending on state of healing.153

Koate-DVI IV

Mild bleeding (superficial or early bleeding): A single 10-unit/kg dose may be sufficient to achieve an in vivo factor VIII level of approximately 20% of normal.158 Repeat only if evidence of further bleeding.158

Moderate bleeding (more serious bleeding episodes including definite hemarthroses, known trauma): Initially, 15–25 units/kg to achieve a plasma factor VIII level of 30–50% of normal.158 If additional therapy is required, give additional doses of 10–15 units/kg every 8–12 hours.158

Severe bleeding (life-threatening bleeding or possible hemorrhage involving vital structures [e.g., CNS, retropharyngeal and retroperitoneal spaces, iliopsoas sheath]): Increase plasma factor VIII level to 80–100% of normal with an initial dose of 40–50 units/kg and a maintenance dosage of 20–25 units/kg every 8–12 hours.158

Major surgery: Increase plasma factor VIII level to approximately 100% with a preoperative 50-unit/kg dose.158 Check plasma factor VIII levels to verify that the expected level is achieved prior to surgery.158 Give additional doses if necessary, every 6–12 hours initially, and for a total of 10–14 days until healing complete.158

Intensity of antihemophilic factor therapy required depends on the type of surgery and postoperative regimen employed; less intensive treatment schedules may provide adequate hemostasis for minor surgical procedures.158

Monoclate-P IV

Mild bleeding: A single infusion may be sufficient to achieve a plasma factor VIII level of ≥30% of normal.167

Moderate bleeding: Initially, 15–25 units/kg to achieve a plasma factor VIII level of 30–50% of normal.167 If needed, give additional doses of 10–15 units/kg every 8–12 hours.167

Severe bleeding (e.g., neck, throat, subperitoneal bleeding): Initially, 40–50 units/kg and a maintenance dosage of 20–25 units/kg given every 8–12 hours may be sufficient to achieve a plasma factor VIII level of 80–100% of normal.167

Minor surgery: Initially, 15–25 units/kg to achieve a plasma factor VIII level of 30–50% of normal; maintenance doses of 10–15 units/kg may be given every 8–12 hours if needed.167

Major surgery: Administer appropriate dosage to achieve plasma factor VIII level of 80–100% of normal 1 hour before surgery; administer a second dose equal to 50% of the initial dose 5 hours later.167 Maintain a plasma factor VIII level of ≥30% of normal for 10–14 days after surgery.167

Routine Prophylaxis of Bleeding Episodes in Hemophilia A IV

Various dosing regimens have been recommended.215 218 231 MASAC states that an antihemophilic factor dosage of 25–50 units/kg 3 times a week or every other day usually is sufficient to maintain trough factor VIII concentrations >1% between infusions.218

Individualize prophylactic regimens; evaluate patients periodically to determine continued need for prophylaxis.218

von Willebrand Disease (Alphanate)

Amount of vWF:RCo and factor VIII contained in each vial of Alphanate is indicated on the label.122 Ratio of vWF:RCo to factor VIII varies depending on the manufacturing lot; therefore, reevaluate dosage of Alphanate for management of von Willebrand disease whenever a different manufacturing lot is indicated on the vial.122

IV

Patients undergoing a minor surgical or invasive procedure: Initially, 60 units/kg of vWF:RCo prior to procedure to achieve a target factor VIII level of 40–50% of normal; follow with additional doses of 40–60 units/kg of vWF:RCo every 8–12 hours as clinically needed for 1–3 days to maintain factor VIII levels at 40–50% of normal.122

Type 1 or type 2 patients undergoing a major surgical or invasive procedure: Initially, 60 units/kg of vWF:RCo prior to procedure to achieve a factor VIII level of 100% of normal; follow with additional dosages of 40–60 units/kg of vWF:RCo every 8–12 hours as clinically needed for 3–7 days to maintain factor VIII levels at 100%.122

Therapeutic goal is to achieve trough factor VIII and vWF:RCo levels >50%; do not exceed 150%.122

von Willebrand Disease (Humate-P) IV

Adjust dosage according to extent and location of bleeding.133 Usually administer dosage of 40–80 units/kg of vWF:RCo (corresponding to 17–33 units/kg of antihemophilic factor) every 8–12 hours; repeat doses for as long as needed based on monitoring of appropriate clinical and laboratory measures.133

Expected levels of vWF:RCo based on expected in vivo recovery of 2% increase per unit/kg of vWF:RCo administered.133 Administration of 1 unit/kg of antihemophilic factor can be expected to result in an increase in circulating vWF:RCo of approximately 5%.133

In all patients with major bleeding, monitor and maintain factor VIII levels according to the usual guidelines for patients with hemophilia A.133

Type 1 (Mild) von Willebrand Disease (Baseline vWF:RCo Activity Typically >30%) IV

Major bleeding (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma, traumatic bleeding) or minor bleeding when use of desmopressin is inadequate or contraindicated: Initially, 40–60 units/kg of vWF:RCo, followed by 40–50 units/kg of vWF:RCo every 8–12 hours for 3 days to maintain a trough vWF:RCo level of >50%.133 Continue with 40–50 units/kg of vWF:RCo daily for up to 7 days.133

Type 1 (Moderate or Severe) von Willebrand Disease (Baseline vWF:RCo Activity Typically <30%) IV

Minor bleeding (e.g., epistaxis, oral bleeding, menorrhagia): 40–50 units/kg of vWF:RCo given as 1 or 2 doses.133

Major bleeding (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma, hemarthrosis, traumatic bleeding): Initially, 50–75 units/kg of vWF:RCo, followed by 40–60 units/kg of vWF:RCo every 8–12 hours for 3 days to maintain a vWF:RCo trough level of >50%.133 Continue with 40–60 units/kg of vWF:RCo daily for up to 7 days.133

Type 2 (All Variants) and Type 3 von Willebrand Disease IV

Minor bleeding (e.g., epistaxis, oral bleeding, menorrhagia): 40–50 units/kg of vWF:RCo given as 1 or 2 doses.133

Major bleeding (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma, hemarthrosis, traumatic bleeding): Initially, 60–80 units/kg of vWF:RCo, followed by 40–60 units/kg of vWF:RCo every 8–12 hours for 3 days to maintain a vWF:RCo trough level of >50%.133 Continue with 40–60 units/kg of vWF:RCo daily for up to 7 days.133

Prevention of Excessive Perioperative Bleeding in von Willebrand Disease

Whenever possible, calculate dosages for surgical prophylaxis based on IVR values.133 If individual IVR values not available, assume IVR of 2% per unit/kg.133 In case of emergency surgery, administer loading dose of 50–60 units/kg of vWF:RCo and closely monitor trough coagulation factor levels.133

To calculate IVR, use the following formula.133 Measure plasma vWF:RCo level at baseline and 30 minutes following a calculated dose.133

IVR = (plasma vWF:RCotime + 30 minutes - plasma vWF:RCobaseline) / calculated dose (in units/kg)

Calculate loading dose (administered 1–2 hours prior to surgery) using the following formula:133

Dose required (units vWF:RCo) = [(target peak plasma vWF:RCo - baseline plasma vWF:RCo) x body weight (in kg)]/IVR

Administer loading doses to achieve specific target peak vWF:RCo and factor VIII levels.133 Additional doses may be necessary to achieve recommended factor VIII levels; because of a higher ratio of vWF:RCo to factor VIII (2.4 to 1), vWF:RCo will increase proportionally more than factor VIII with increasing doses.133

Administer initial maintenance dose equal to one-half the loading dose (irrespective of any additional loading doses given to meet target factor VIII goals); follow with additional maintenance doses based on trough plasma vWF:RCo and factor VIII levels.133 Frequency of administration depends on individual pharmacokinetic parameters; in the absence of such data, administer every 8 hours initially.133

Monitor trough vWF:RCo and factor VIII levels at least once daily, and during and after surgery.133 Modify dose and/or frequency of antihemophilic factor administration if hemostasis is insufficient or measured trough coagulation factor levels are not within recommended range.133 Because factor VIII is the main predictor of surgical hemostasis, some clinicians recommend monitoring factor VIII levels every 12 hours on the day a dose is administered, then every 24 hours thereafter.244 Determine duration of therapy based on hemostatic response.133

IV

Major surgery: Administer appropriate loading dose to achieve a target peak plasma vWF:RCo level of 100% and a peak plasma factor VIII level of 80–100%.133 Give initial maintenance dose equal to one-half the loading dose and subsequent doses to achieve target trough vWF:RCo levels of >50% (>50% of factor VIII activity) for up to 3 days following surgery and target trough vWF:RCo levels of >30% (>30% of factor VIII activity) after day 3.133 Minimum duration of treatment is 72 hours.133

Minor surgery: Administer appropriate loading dose to achieve a target peak plasma vWF:RCo level of 50–60% and a peak plasma factor VIII level of 40–50%.133 Give initial maintenance dose equal to one-half the loading dose and subsequent doses to achieve target trough plasma vWF:RCo levels of ≥30% for up to 3 days following surgery and target trough factor VIII levels >30% after day 3.133 Minimum duration of treatment is 48 hours.133

Oral surgery: Administer appropriate loading dose to achieve a target peak vWF:RCo level of 50–60% and a peak plasma factor VIII level of 40–50%.133 Give initial maintenance dose equal to one-half the loading dose and subsequent doses to achieve target trough vWF:RCo levels of ≥30% for up to 3 days following surgery and target trough factor VIII levels >30% after day 3.133 Minimum duration of treatment is 8–12 hours.133

Prescribing Limits

Pediatric Patients

Hemophilia A IV

Hemofil-M: Maximum infusion rate 10 mL/minute.153

von Willebrand Disease IV

Alphanate: Maximum infusion rate 10 mL/minute.122

Humate-P: Maximum infusion rate 4 mL/minute.133

Adults

Hemophilia A IV

Alphanate, Hemofil-M: Maximum infusion rate 10 mL/minute.122 153 Higher rates may result in vasomotor reactions.122

Humate-P: Maximum infusion rate 4 mL/minute.133

von Willebrand Disease IV

Alphanate: Maximum infusion rate 10 mL/minute.122

Humate-P: Maximum infusion rate 4 mL/minute.133

Interactions for Antihemophilic Factor (Human)

No formal drug interaction studies to date.122

Uses of Antihemophilic Factor

  • It is used to treat hemophilia.
  • It is used to treat or prevent bleeding.

What are some other side effects of Antihemophilic Factor?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Feeling nervous and excitable.
  • Headache.
  • Stomach pain.
  • Upset stomach.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take antihemophilic factor or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to antihemophilic factor. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Adverse Reactions

<1% (Limited to important or life-threatening): Acute hemolytic anemia, anaphylaxis (rare), blurred vision, chest tightness, chills, drowsiness, fever, headache, hemorrhagic diathesis, hypersensitivity reaction (rare), increased factor VIII inhibitors, increased serum fibrinogen, jitteriness, lethargy, nausea, pain at injection site, stomach discomfort, tingling sensation, urticaria, vasomotor symptoms (with rapid infusion), vomiting

For Healthcare Professionals

Applies to antihemophilic factor: intravenous kit, intravenous powder for injection

Nervous system

Nervous system side effects have included headache, dizziness, somnolence, and asthenia.[Ref]

Respiratory

Respiratory side effects have included dyspnea and rhinitis.[Ref]

Musculoskeletal

Musculoskeletal side effects have included arthralgia.[Ref]

Local

Local side effects have included injection site pain.[Ref]

General

General side effects have included pyrexia and chills.[Ref]

Gastrointestinal

Gastrointestinal side effects have included nausea, diarrhea, and vomiting.[Ref]

Dermatologic

Dermatologic side effects have include pruritus, rash, and urticaria.[Ref]

Cardiovascular

Cardiovascular side effects have included hemorrhage, hypotension, and vasodilatation.[Ref]

Some side effects of antihemophilic factor may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Adverse Reactions

Allergic-type reactions may result from the administration of Antihemophilic Factor (Human) preparations. 10 , 11

Ten adverse reactions related to 7 infusions were observed during a total of 1053 infusions performed during the clinical study of Koàte-DVI, for a frequency of 0.7% infusions associated with adverse reactions. All reactions were mild and included tingling in the arm, ear, and face, blurred vision, headache, nausea, stomach ache, and jittery feeling. 2

References

  1. Hershgold EJ, Pool JG, Pappenhagen AR: The potent antihemophilic globulin concentrate derived from a cold insoluble fraction of human plasma: characterization and further data on preparation and clinical trial. J Lab Clin Med 67(1):23-32, 1966.
  2. Data on file at Bayer Corporation.
  3. Aronson DL: Factor VIII (antihemophilic globulin). Semin Thromb Hemostas 6(1):12-27, 1979.
  4. Britton M, Harrison J, Abildgaard CF: Early treatment of hemophilic hemarthroses with minimal dose of new factor VIII concentrate. J Pediatr 85(2):245-7, 1974.
  5. Winkelman L., Feldman PA, Evan DR: Severe heat treatment of lyophilised coagulation factors in Virus Inactivation in Plasma Products. Curr Stud Hematol Blood Transfus. Morgenthaler J-J (ed.), Basel, Karger, 1989, No. 56, pp. 55-69.
  6. Skidmore SJ, Pasi KJ, Mawson SJ, et al: Serological evidence that dry heating of clotting factor concentrates prevents transmission of non-A, non-B hepatitis. J. Med Virol. 30(1):50-2, 1990.
  7. Hart HF, Hart WG, Crossley J, et al: Effect of terminal (dry) heat treatment on non-enveloped viruses in coagulation factor concentrates. Vox Sang 67(4):345-50, 1994.
  8. National Hemophilia Foundation Medical and Scientific Advisory Council. Hemophilia Information Exchange-AIDS Update: Recommendations concerning AIDS and the treatment of hemophilia HIV infection. Section I.G. (Rev. Jan., 1988).
  9. Safety of therapeutic products used for hemophilia patients. MMWR 37(29):441-4, 449-50, 1988.
  10. Eyster ME, Bowman HS, Haverstick JN: Adverse reactions to factor VIII infusions. [letter] Ann Intern Med 87(2):248, 1977.
  11. Prager D, Djerassi I, Eyster ME, et al: Pennsylvania state-wide hemophilia program: summary of immediate reactions with the use of factor VIII and factor IX concentrate. Blood 53(5):1012-3, 1979.
  12. Kasper CK: Complications of hemophilia A treatment: factor VIII inhibitors. Ann NY Acad Sci 614:97-105, 1991.
  13. Mariani G, Hilgartner M, Thompson AR, et al: Immune Tolerance to Factor VIII: International Registry Data. Adv Exp Med Biol 386:201-8, 1995.
  14. DiMichele D: Hemophilia 1996, New Approach to an Old Disease. Pediatr Clin North Am 43(3):709-35, Jun 1995.
  15. Abildgaard CF, Simone JV, Corrigan JJ, et al: Treatment of hemophilia with glycine-precipitated factor VIII. N Engl J Med 275(9):471-5, 1966.
  16. Britton M, Harrison J, Abildgaard CF: Early treatment of hemophilic hemarthroses with minimal dose of new factor VIII concentrate. J Pediatr 85(2):245-7, 1974.
  17. Abildgaard CF: Current concepts in the management of hemophilia. Semin Hematol 12(3):223-32, 1975.
  18. Hilgartner MW: Factor replacement therapy. In: Hilgartner MW, Pochedly C, eds.: Hemophilia in the child and adult. New York, Raven Press, 1989, pp 1-26.
  19. Kasper CK, Dietrich SL: Comprehensive management of haemophilia. Clin Haematol 14(2):489-512, 1985.
  20. Nilsson IM, Berntorp E, Löfqvist T, et al: Twenty-five years' experience of prophylactic treatment in severe haemophilia A and B. J Intern Med 232(1):25-32, 1992.

Bayer

Bayer Corporation

Pharmaceutical Division

Elkhart, IN 46515 USA

U.S. License No. 8                  08848621

Printed in the USA.      (Rev. April 2003)

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