Antihemophilic Factor (Human)

Class: Hemostatics
VA Class: BL500
CAS Number: 9001-27-8
Brands: Alphanate, Hemofil-M, Humate-P, Koate-DVI, Monarc-M, Monoclate-P

Introduction

Preparation of antihemophilic factor (blood coagulation factor VIII) prepared from pooled human plasma from suitable whole-blood donors.122 133 152 153 158 167

Uses for Antihemophilic Factor (Human)

Hemophilia A

Prevention and control of hemorrhagic episodes in individuals with a deficiency of coagulation factor VIII (antihemophilic factor) associated with hemophilia A (classic hemophilia).122 133 152 153 158 167

Maintenance of hemostasis in patients with hemophilia A undergoing emergency or elective surgery.122 133 152 153 158 167

Because of an increased risk of transmission of human viruses (e.g., HIV, hepatitis A virus [HAV], hepatitis B virus [HBV], hepatitis C virus [HCV]) and other transmissible disease agents (e.g., agents for Creutzfeldt-Jakob disease [CJD], variant CJD [vCJD]) with plasma-derived antihemophilic factor compared with antihemophilic factor (recombinant), the Medical and Scientific Advisory Council (MASAC) of the National Hemophilia Foundation and other experts recommend antihemophilic factor (recombinant) as the preparation of choice in patients with hemophilia A.103 111 134 170 176 218 Recombinant and plasma-derived preparations of antihemophilic factor are similar and produce comparable hemostatic effects.134 170

Antihemophilic factor replacement therapy generally is required in patients with mild to moderate hemophilia A who do not respond adequately to desmopressin or those with moderate to severe hemophilia A and factor VIII levels <5% of normal.111 154 160 175 177 183 215

Also used for routine prophylaxis (i.e., administration at regular intervals) to prevent or reduce frequency of hemorrhagic events and preserve joint function.158 215 224 225 226 231 MASAC recommends prophylaxis in patients with severe hemophilia A (factor VIII activity <1%) after careful consideration of risks versus benefits.218

Hemophilia A with Inhibitors to Antihemophilic Factor

Prevention and treatment of bleeding in patients with hemophilia A who have developed relatively low levels of inhibitors (alloantibodies) to factor VIII.152 153 154 160 176 179 180 181 182 184 186 215 (See Development of Inhibitors to Antihemophilic Factor under Cautions.) May be effective in those whose inhibitor levels have historically remained <5–10 Bethesda units/mL.154 160 182 184 186 Some manufacturers state antihemophilic factor may be effective in patients with inhibitor levels ≤10 Bethesda units/mL;152 153 other clinicians recommend use of these preparations in those with inhibitor levels <5 Bethesda units/mL.215 239 240

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Has been used to induce immune tolerance as a long-term strategy to eradicate or suppress further antibody production.158 160 188 189 190 191 222 227 Such therapy eliminates risk of anamnesis with continued use of antihemophilic factor (human).160 188 189 190 191 While some experts state there is insufficient evidence to recommend use of immune tolerance therapy in patients with inhibitors,227 MASAC recommends such therapy for eradication of high-titer inhibitors.111

Other therapeutic options for patients with inhibitors include bypassing agents such as anti-inhibitor coagulant complex (activated prothrombin complex concentrate [APCC]), factor VIIa (recombinant), or certain factor IX complex preparations (prothrombin complex concentrates [PCCs]).111 134 154 160 176 180 182 213 216 217 220 227 MASAC currently recommends use of a bypassing agent in hemophilia A patients with inhibitors to prevent or control bleeding in settings where antihemophilic factor preparations would otherwise be used, including before and after surgery and physical therapy.220

Management of hemophilia A in patients with inhibitors may be difficult and consultation with a hemophilia treatment center is strongly recommended.154 160 176 184 215

Acquired Hemophilia

Has been used to control bleeding in patients without hemophilia A who spontaneously acquire inhibitors (autoantibodies) to factor VIII.122 152 153 Autoantibodies are similar to but more heterogeneous than the alloantibodies that develop in patients with hemophilia A.176 180 182 185

Management of acquired hemophilia not well established.154 176 179 180 181 182 184 185 Antihemophilic factor (human or recombinant) may be effective in patients with low levels of inhibitors.152 153 160 184 185 Other treatment options include immunosuppressive therapy, desmopressin, or bypassing agents.160 176 179 180 181 182 184 185 186 213 214

von Willebrand Disease

Used when necessary to prevent or control bleeding in certain individuals with von Willebrand disease.111 122 133 161 201 244 Only preparations of antihemophilic factor (human) containing both factor VIII and von Willebrand factor should be used.111 122 133 161 201 Generally recommended in patients with type 2 or type 3 von Willebrand disease and those with type 2A, 2M, or 2N disease who are unresponsive to desmopressin.111 161 201 244

Humate-P is indicated for the management of spontaneous or trauma-induced bleeding episodes and for prevention of excessive bleeding during and after surgery in adult and pediatric patients with severe von Willebrand disease, and in those with mild to moderate von Willebrand disease when use of desmopressin is known or suspected to be inadequate.133 Designated an orphan drug by FDA for treatment of von Willebrand disease.169

Alphanate is indicated in adult and pediatric patients with von Willebrand disease who are undergoing surgical and/or invasive procedures and cannot receive desmopressin because the drug is ineffective or contraindicated;122 designated an orphan drug by FDA for this use.169 Alphanate is not indicated for patients with type 3 von Willebrand disease undergoing major surgery.122 232

Limited data suggest that certain other intermediate- or high-purity antihemophilic factor (human) preparations (i.e., Koate-DVI) that contain sufficient quantities of von Willebrand factor: Ristocetin cofactor (vWF:RCo) and von Willebrand factor antigen (wWF:AG) may be effective in the management of von Willebrand disease.111 161 201 244

Very high purity preparations (Hemofil-M, Monarc-M, Monoclate-P) of antihemophilic factor (human) prepared using immunoaffinity purification should not be used in the treatment of von Willebrand disease; such preparations do not contain adequate amounts of von Willebrand factor.111 152 153 161 167 201 244

Antihemophilic Factor (Human) Dosage and Administration

General

  • In patients with hemophilia A, confirm deficiency of factor VIII prior to initiating therapy;133 152 153 158 continue monitoring factor VIII levels periodically during treatment to individualize dosage and assess response to therapy.122 133 158 (See Laboratory Monitoring under Cautions.)

  • In patients with von Willebrand disease, confirm deficiency of vWF:RCo prior to initiating therapy;133 continue monitoring vWF:RCo levels periodically during treatment to individualize dosage and assess response to therapy.133 (See Laboratory Monitoring under Cautions.)

  • Correct factor VIII and/or vWF:RCo deficiency prior to surgical procedures.158 167 215

Administration

IV Administration

Administer by slow IV injection or by IV infusion over several minutes.122 133 152 153 158 167

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

Administer using plastic syringes only; antihemophilic factor (human) may adhere to glass.122 133 152 153 167

Filter solution prior to administration.122 133 152 153 158 215

Instructions on reconstitution, dilution, and administration vary according to preparation; consult manufacturer’s labeling for specific information on each antihemophilic factor (human) product.122 133 152 153 158 167

Reconstitution

Prior to reconstitution, allow injection concentrate and diluent to warm to room temperature; do not exceed 37°C.122 133 152 153 158 167 Solution may precipitate if administered below room temperature.a

Reconstitute antihemophilic factor (human) concentrate with diluent provided by manufacturer.122 133 152 153 158 167

Gently swirl solution to dissolve powder completely; do not shake.122 133 152 153 167

Rate of Administration

Individualize infusion rates according to patient response and comfort.158 167 Monitor pulse rate before and during infusion.152 153 Slow infusion rate or temporarily discontinue therapy if there is a substantial increase in pulse rate.152 153

Alphanate, Hemofil-M, Monarc-M: Administer at a rate ≤10 mL/minute.122 152 153

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).122 133 152 153 158 167 168 One unit is approximately equivalent to amount of factor VIII or von Willebrand factor:Ristocetin cofactor (vWF:RCo) in 1 mL of fresh pooled human plasma.122 133 158 167

Individualize dosage and duration of therapy based on degree of factor VIII deficiency (measuring factor VIII levels prior to and at regular intervals during therapy), desired factor VIII levels, patient’s weight, type and severity of bleeding, presence of factor VIII inhibitors, and clinical response.122 133 158 167 215

Use the following calculations and dosage guidelines (based on the degree of hemorrhage or type of surgery) for administering the drug in patients with hemophilia A.122 133 152 153 158 167

These calculations and suggested dosage regimens are only approximations and should not preclude appropriate clinical monitoring, laboratory determinations, and individualization of dosage based on the hemostatic requirements of patients.122 133 152 153 158 167 Perform serial assays of factor VIII at suitable intervals to ensure that adequate levels have been attained and maintained.122 133 152 153 158 167 Consult manufacturers’ prescribing information for specific dosage recommendations for each antihemophilic factor (human) preparation.122 133 152 153 158 167

Careful control of the dose is especially important in cases of life-threatening bleeding or major surgery.152 153 If calculated dosage is ineffective in achieving adequate factor VIII levels or if bleeding is not controlled, consider the possibility that inhibitors to antihemophilic factor may have developed.122 152 153 215 (See Development of Inhibitors to Antihemophilic Factor under Cautions.) Some patients with inhibitors may require higher or more frequent doses.122 152 153 158

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

Dosage required to achieve desired factor VIII levels:122 152 153 158 167

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 dosage:122 152 153 158 167

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

Pediatric Patients

Hemophilia A
Alphanate
IV

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

Pediatric patients >16 years of age with moderate hemorrhage (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 hemorrhage (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; 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

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 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

Hemofil-M, Monarc-M

The manufacturer of Hemofil-M and Monarc-Mstates that there are no clear indications in labeling concerning use of Hemofil-M and Monarc-M in pediatric patients.152 153 234

Humate-P
IV

Adequate and well-controlled studies evaluating use in pediatric patients with hemophilia A not available.133 When immediate control of bleeding is necessary in a pediatric patient, manufacturer recommends that the general recommendations for dosage and administration in adults be considered.133 (See Humate-P dosage recommendations for adults under Dosage and Administration.)

Monoclate-P
IV

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

Moderate hemorrhage: 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 hemorrhage (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
IV

Various dosing regimens have been recommended; optimal dosage remains to be established.215 218 225 231 Dosages of 25–40 units/kg every other day (minimum 3 times a week) usually recommended.215 231 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

Evaluate patients periodically to determine continued need for prophylaxis; some patients may require life-long prophylaxis.218

von Willebrand Disease (Alphanate)

Amount of von Willebrand factor:Ristocetin cofactor (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 should be reevaluated whenever a different manufacturing lot is indicated on the vial.122

IV

Surgical or invasive procedures: Initially, 75 units/kg of vWF:RCo prior to procedure; follow with additional doses of 50–75 units/kg of vWF:RCo every 8–12 hours as clinically needed.122 May reduce dosage after third postoperative day; continue treatment until healing is complete.122

von Willebrand Disease (Humate IV-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

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 hemorrhage (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma, traumatic hemorrhage) and when use of desmopressin is inappropriate: 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 hemorrhage (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 hemorrhage (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma, hemarthrosis, traumatic hemorrhage): 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 hemorrhage (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 hemorrhage (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma, hemarthrosis, traumatic hemorrhage): 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 Bleeding During and After Surgery

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 dose of 60 units/kg of vWF:RCo.133

IVR = (Plasma vWF:RCotime + 30 minutes - Plasma vWF:RCobaseline) / 60 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

Hemophilia A
Alphanate
IV

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

Moderate hemorrhage (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 hemorrhage (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

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 hemorrhage (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 hemorrhage (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 hemorrhage (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, Monarc-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.152 153 To maintain an adequate level, administer doses every 12–24 hours for 1–3 days until bleeding resolves (indicated by relief of pain) or healing achieved.152 153

More extensive hemarthrosis, muscle hemorrhage, or hematoma: Administer appropriate dosage to achieve peak plasma factor VIII postinfusion level of 30–60% of normal.152 153 Give doses every 12–24 hours for 3 days or longer until pain and disability resolve.152 153

Life-threatening bleeding (e.g., head injury, throat bleeding, severe abdominal pain): Administer appropriate dosage to achieve a peak plasma factor VIII postinfusion level of 60–100% of normal.152 153 Give doses every 8–24 hours until bleeding resolves.152 153

Minor surgery (e.g., tooth extraction): Administer appropriate dosage to achieve a peak plasma factor VIII postinfusion level of 60–80% of normal.152 153 A single infusion given in conjunction with an oral antifibrinolytic agent usually is sufficient in about 70% of patients.152 153

Major surgery: Administer appropriate dosage to achieve peak plasma factor VIII pre- and postoperative levels of 80–100% of normal.152 153 Repeat doses every 8–24 hours depending on state of healing.152 153

Koate-DVI
IV

Mild hemorrhage (superficial or early hemorrhage): 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 hemorrhage (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 hemorrhage (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 hemorrhage: A single infusion may be sufficient to achieve a plasma factor VIII level of ≥30% of normal.167

Moderate hemorrhage: 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 hemorrhage (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
IV

Various dosing regimens have been recommended; optimal dosage remains to be established.215 218 231 Dosages of 25–40 units/kg every other day (minimum 3 times a week) usually recommended.215 231 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

Evaluate patients periodically to determine continued need for prophylaxis.218

Acquired Hemophilia
IV

When used in patients with acquired factor VIII inhibitors ≤10 Bethesda units/mL, dosages of antihemophilic factor (human) should be controlled by frequent monitoring of plasma factor VIII levels.152 153 Individualize treatment.122

von Willebrand Disease (Alphanate)

Amount of von Willebrand factor:Ristocetin cofactor (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

Minor surgical or invasive procedures: Initially, 60 units/kg of vWF:RCo prior to procedure; follow with additional doses of 40–60 units/kg of vWF:RCo every 8–12 hours as clinically needed.122 Maintain a vWF level of 40–50% of normal for 1–3 days after procedure.122 May reduce dosage after third postoperative day, but continue treatment until healing is complete.122

Major surgical or invasive procedures: Initially, 60 units/kg of vWF:RCo prior to procedure; follow with additional dosages of 40–60 units/kg of vWF:RCo every 8–12 hours as clinically needed.122 Maintain a vWF level of 40–50% of normal for at least 3–7 days after procedure.122 May reduce dosage after third postoperative day, but continue treatment until healing is complete.122

von Willebrand Disease (Humate IV-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 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

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 hemorrhage (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma, traumatic hemorrhage) and when use of desmopressin is inappropriate: 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 hemorrhage (e.g., epistaxis, oral bleeding, menorrhagia): 40–50 units/kg of vWF:RCo given as 1 or 2 doses.133

Major hemorrhage (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma, hemarthrosis, traumatic hemorrhage): 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 hemorrhage (e.g., epistaxis, oral bleeding, menorrhagia): 40–50 units/kg of vWF:RCo given as 1 or 2 doses.133

Major hemorrhage (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma, hemarthrosis, traumatic hemorrhage): 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 Bleeding During and After Surgery

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.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 dose of 60 units/kg of vWF:RCo.133

IVR = (Plasma vWF:RCotime + 30 minutes - Plasma vWF:RCobaseline) / 60 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

Alphanate (Pediatric patients >16 years of age): Maximum infusion rate of 10 mL/minute.122 Higher rates may result in vasomotor reactions.122

Adults

Hemophilia A
IV

Alphanate, Hemofil-M, Monarc-M: Maximum infusion rate of 10 mL/minute.122 152 153 Higher rates may result in vasomotor reactions.122

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

Cautions for Antihemophilic Factor (Human)

Contraindications

  • Known hypersensitivity to commercially available antihemophilic factor or von Willebrand factor preparations or any ingredient in the formulations.133

  • Known hypersensitivity to murine protein (Hemofil-M, Monarc-M, Monoclate-P).152 153 167

  • The manufacturers state that there are no known contraindications to the use of Alphanate or Koate-DVI.122 158

Warnings/Precautions

Warnings

Risk of Transmissible Agents in Plasma-derived Preparations

Improved donor screening, viral-inactivating procedures (e.g., solvent/detergent, heat treatment), and/or immunoaffinity chromatography procedures have reduced but not completely eliminated risk of pathogen transmission with plasma-derived antihemophilic factor preparations.103 111 122 133 152 153 154 158 167 183 215

Possibility still exists for transmission of human viruses (e.g., HIV, HAV, HBV, HCV) and other infectious agents (e.g., transfusion-transmitted virus [TTV], CJD, vCJD, transmissible spongiform encephalopathy [TSE] diseases, other unknown viruses).103 111 122 133 152 153 154 158 167 174 183 196 199 200 202

Current viral-depleting methods apparently can inactivate lipid-encapsulated viruses, such as HBV, HIV-1, HIV-2, and HCV; however, these methods are less effective against viruses that do not have a lipid envelope (e.g., parvovirus B19, HAV).103 111 133 167 195

Carefully weigh risk of pathogen transmission versus benefits of antihemophilic factor (human) prior to initiating therapy.103 122 152 153 158 Report any suspected infections associated with the drug to the manufacturer, FDA, and CDC.111 122 133 152 153 158 167

Risk of Hepatitis

Risk of hepatitis A or hepatitis B infection.111 133 233 235

Monitor closely for signs and symptoms of hepatitis A during therapy.133 (See Advice to Patients.)

Experts recommend administration of hepatitis B vaccine to all individuals with bleeding disorders who are seronegative and have not already been vaccinated; vaccination is recommended at birth or at time of diagnosis.111 122 133 158 197

Immunization with hepatitis A vaccine is recommended for all individuals ≥12 months of age with hemophilia A or other congenital bleeding disorders who are HAV seronegative.111 233 235

Risk of HIV Infection

Potential vehicle for transmission of HIV.111 HIV seroconversion reported in the past in patients who received blood or blood products from donors not screened for HIV and/or prepared using suboptimal viral-inactivating procedures.100 101 102 107 127 136 142 147 148 149 (See Risk of Transmissible Agents in Plasma-derived Preparations under Cautions.)

No reports to date of HIV seroconversion with currently available antihemophilic factor (human) preparations.111 152 153

Risk of Creutzfeldt-Jakob Disease

Theoretical possibility of transmitting causative agent of CJD or vCJD.103 122 174 202 Several probable cases of vCJD transmission reported from transfusion of human RBCs.174 219 However, no cases of CJD or vCJD from antihemophilic factor preparations reported to date.103 For further information on CJD and vCJD precautions related to blood and blood products, consult the FDA’s guidance for industry ().202

Risk of West Nile Virus

Evidence of West Nile virus (WNV) transmission through transplanted organs (e.g., heart, liver, kidney) and blood products.205 208 209 237 However, WNV transmission through commercially available factor VIII preparations unlikely due to current viral-inactivating procedures.207 237

For further information on WNV precautions related to blood and blood products, consult the FDA’s guidance for industry ().237

Thromboembolism

Thromboembolic events reported in patients with von Willebrand disease receiving antihemophilic factor (human), usually occurring in setting of known thrombotic risk factors.122 133 Preliminary reports indicate higher risk in females.122 133

Although a causal relationship not established, high levels of endogenous factor VIII have been associated with thrombosis.122 133

Exercise caution when using coagulation factor replacement therapy in all von Willebrand disease patients with high thrombotic risk.122 133 Consider use of antithrombotic measures.122

Development of Inhibitors to Antihemophilic Factor

Risk for development of inhibitors (alloantibodies) to factor VIII following antihemophilic factor therapy.110 122 134 160 167 179 180 181 182 194 222 Inhibitors reported in about 20–30% of patients receiving antihemophilic factor (human), usually within the first 10–20 days of treatment.167 215 223

Inhibitors may diminish or neutralize response to therapy.122 164 165 166 169 222 Anamnestic responses and increased levels of inhibitor possible with continued administration of drug.160 176 179 180 182 194 215

Monitor for development of antihemophilic factor inhibitors during treatment with clinical observation and appropriate laboratory tests.152 153 Perform screening tests for inhibitors routinely and immediately prior to surgery.215 222 The World Federation of Hemophilia recommends that children be screened every 3–12 months or every 10–20 days during treatment, whichever occurs first.215 Screen adults whenever clinically indicated.215 Consider possibility that inhibitors may have developed in patients who fail to respond to adequate dosages of antihemophilic factor (human) or those with unexpectedly prolonged aPTT.122 152 153 158 215 222

Consider several factors (e.g., severity and location of bleeding, type [low- or high-responding] and titer of inhibitor, history of anamnestic response, previous response to these preparations) when treating patients with inhibitors.111 154 160 176 179 181 182 184 215 216 Consultation with a hemophilia treatment center strongly recommended.111 154 158 160 176 184 215 Carefully monitor such patients, especially when surgical procedures indicated.122 164 165 166 169 Use clinical response and frequent assessment of factor VIII levels to guide treatment.152 153 158 Higher than recommended dosages may be required to achieve hemostasis in patients with inhibitors.122

Risk of developing inhibitors to von Willebrand factor currently not known; some reports suggest possible development of antibodies to von Willebrand factor following replacement therapy in patients with type 3 von Willebrand disease.122

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (hives, generalized urticaria, tightness of the chest, wheezing, hypotension, anaphylaxis) reported.122 133 152 153

The principal protein in Hemofil M and Monarc-M is albumin human.152 153 Adverse reactions associated with IV administration of albumin are rare; however, nausea, fever, chills, and urticaria have been reported in patients receiving the protein.152 153

If hypersensitivity reaction occurs, discontinue drug immediately and initiate appropriate therapy.122 152 153 167 When using Alphanate, consider using product from a different lot if a reaction occurs.122

Antibody Formation to Trace Animal Proteins

Some preparations of antihemophilic factor (human) contain trace amounts of animal proteins (Hemofil-M, Monarc-M, Monoclate-P) which may stimulate antibody production and cause hypersensitivity reactions.152 153 167

Latex Sensitivity

Packaging components for some preparations (e.g., Hemofil-M, Koate-DVI, Monarc-M) may contain natural latex proteins; take appropriate precautions if injection is handled by or administered to individuals with a history of natural latex sensitivity.152 153 158 238 241

General Precautions

Hematologic Effects

Some preparations of antihemophilic factor (human) contain trace amounts of blood groups A and B isohemagglutins; intravascular hemolysis and anemia possible, especially when large or frequently repeated doses are given to individuals with blood groups A, B, or AB.122 133 158

Monitor for signs of intravascular hemolysis and progressive anemia (performing hematocrit and direct antiglobulin [Coombs test]) in such individuals.122 133 158 167 If hemolysis or hemolytic anemia occurs, discontinue therapy and initiate appropriate treatment; consider administration of serologically compatible RBCs from blood group O.122

Laboratory Monitoring

To ensure adequate therapeutic response, monitor factor VIII levels prior to and at regular intervals during therapy, especially in patients with major bleeding or who require surgery.122 152 153 158 167

To ensure adequate therapeutic response, monitor vWF:RCo levels prior to and at least once daily during therapy, and during and after surgery in patients with von Willebrand disease.133

Monitor for development of inhibitors during treatment, prior to surgery, and when switching between different antihemophilic factor preparations.215 (See Development of Inhibitors to Antihemophilic Factor under Cautions.)

Specific Populations

Pregnancy

Category C.122 133 152 153 158 167

Lactation

Not known whether antihemophilic factor (human) is distributed into human milk.234 236

Pediatric Use

Alphanate: Safety and efficacy not established in children ≤16 years of age with hemophilia A.122 In a well controlled clinical study in patients who previously received factor VIII concentrates for hemophilia A, the single pediatric patient receiving Alphanate responded similarly when compared with adult patients; no adverse events were reported.122 Also used in pediatric patients with von Willebrand disease undergoing surgical and/or invasive procedures.122

Hemofil-M: Manufacturer states that there are no clear indications in labeling concerning use in pediatric patients.234

Humate-P: No adequate and well-controlled studies in pediatric patients with hemophilia A.133 Long-term evaluation of joint damage not available for pediatric patients; joint damage may result from suboptimal treatment of hemarthroses.133 When necessary for immediate control of bleeding in pediatric patients with hemophilia A, manufacturer recommends that the general recommendations for dosage and administration in adults be considered.133 Safety and efficacy have been established for management of bleeding in infants, children, and adolescents with von Willebrand disease; safety and efficacy not established in neonates with von Willebrand disease.133

Koate-DVI: Has not been studied in pediatric patients; manufacturer states that the drug has been used extensively in pediatric patients.158 Adverse effects reported in pediatric patients generally have been similar to those reported in adults.158

Monarc-M: Manufacturer states that there are no clear indications in labeling concerning use in pediatric patients.234

Monoclate-P: Safety and efficacy established in children with hemophilia A; manufacturer recommends following adult dosage guidelines.167

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients.133 167 Use with caution due to greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly.167 Individualize dosage.133 167

Common Adverse Effects

Hemophilia A: Urticaria,122 133 152 153 fever,122 133 152 153 chills,122 133 152 153 167 nausea,122 133 152 153 158 167 chest tightness,133 152 153 stinging at infusion site,122 167 paresthesia,133 158 headache,122 158 rash,133 pruritus,133 edema,133 vasodilation,133 postoperative hemorrhage,133 vomiting,122 pain,122 133 somnolence,122 lethargy,122 jitteriness,158 abdominal pain,158 blurred vision.158

Von Willebrand disease: Urticaria,133 chest tightness,133 rash,122 133 pruritus,122 133 chills,122 133 paresthesia,122 133 edema,122 133 phlebitis,133 pharyngitis,122 headache,122 133 fever,133 pseudothrombocytopenia,133 extremity pain,133 vasodilation,133 hypervolemia,133 constipation,133 urinary retention,133 dizziness,133 postoperative complications (e.g., hemorrhage,133 nausea,133 pain133 ).

Interactions for Antihemophilic Factor (Human)

No formal drug interaction studies to date.122

Antihemophilic Factor (Human) Pharmacokinetics

Absorption

Bioavailability

Following IV administration, peak plasma concentrations of factor VIII generally occur 10–15 minutes after end of infusion; may occur up to 1–2 hours later.223

Plasma Concentrations

Following IV infusion over 5–15 minutes, plasma concentrations of factor VIII increase by approximately 0.02–0.025 unit/mL per units/kg administered.223

Duration

Von Willebrand disease: Decreased bleeding time generally persists for <6 hours.122

Distribution

Extent

Circulates in plasma; minimally distributed (about 14%) outside vascular system.223

Does not readily cross placenta.a

Not known whether antihemophilic factor (human) is distributed into human milk.234 236

Plasma Binding

Binds noncovalently to von Willebrand factor.110 154 160 175 194 223

Elimination

Elimination Route

Rapidly cleared from plasma following IV administration.a Possibly eliminated partly via reticuloendothelial system.223

Half-life

Factor VIII: About 12 hours (range: 8–18 hours).122 133 152 153 158 167 a

Von Willebrand factor: Approximately 7–11 hours.122 133

Special Populations

Possible increased clearance of factor VIII in patients with severe von Willebrand disease.223

Stability

Storage

Parenteral

Powder for Infusion

Alphanate: 2–8°C (avoid freezing to prevent damage to the diluent vial); may store at room temperature ≤30°C up to 2 months.122 Do not refrigerate after reconstitution; use solution within 3 hours of reconstitution.122

Hemofil-M: 2–8°C (avoid freezing to prevent damage to the diluent vial) or at room temperature ≤30°C up to expiration date.153 Do not refrigerate after reconstitution; use solution within 3 hours of reconstitution.153

Humate-P: ≤25°C up to expiration date; avoid freezing.133 Do not refrigerate after reconstitution; use solution within 3 hours of reconstitution.133

Koate DVI: 2–8°C (avoid freezing to prevent damage to the diluent vial); may store at room temperature ≤25°C up to 6 months.158 Do not refrigerate after reconstitution; use solution within 3 hours of reconstitution.158

Monarc-M: 2–8°C (avoid freezing to prevent damage to the diluent vial) or at room temperature ≤30°C up to expiration date.152 Do not refrigerate after reconstitution; use solution within 3 hours of reconstitution.152

Monoclate-P: 2–8°C (avoid freezing to prevent damage to the diluent vial) up to expiration date or store at room temperature ≤25°C for up to 6 months.167 Use solution within 3 hours of reconstitution.167

Actions

  • Factor VIII is essential for blood clotting and maintenance of hemostasis.110 122 123 134 152 153 154 155 160 175 194

  • Patients with hemophilia A (classic hemophilia) have decreased levels of endogenous factor VIII or dysfunctional factor VIII, resulting in a hemorrhagic tendency and clinical manifestations such as bleeding into soft tissues, muscles, and weight-bearing joints.110 123 134 160 175 194

  • Decreased levels of endogenous factor VIII also may occur in patients with von Willebrand disease who have levels of vWF that are insufficient for in vivo stabilization of factor VIII.123 134 176 177

  • Clinical severity and frequency of bleeding in patients with hemophilia A correlate with the degree of deficiency in factor VIII activity.110 123 134 154 194 Patients with mild hemophilia A generally have >5% of normal activity, those with moderate disease generally have 1–5% of normal activity, and those with severe disease have <1% of normal activity.110 123 160 194

  • Administration of antihemophilic factor (human) to patients with hemophilia A results in increased plasma levels of factor VIII and temporarily corrects the coagulation defect in these patients.122 152 153 158 160 194

  • Provides exogenous source of von Willebrand factor (Alphanate, Humate-P); decreases bleeding time and temporarily corrects coagulation defect in patients with von Willebrand disease.122 133 Von Willebrand factor promotes platelet adhesion and aggregation on damaged vascular endothelium; binds noncovalently to factor VIII, and stabilizes and protects factor VIII from degradation.110 133 154 160 175 194 223

  • Prepared using different methods (e.g., precipitation, gel filtration, chromatography, ultrafiltration) to isolate and purify factor VIII and von Willebrand factor (for Alphanate and Humate-P).122 133 152 153 158 167

  • Undergoes viral inactivation processes (solvent/detergent, heat treatment [pasteurization, dry heat]) to reduce risk of viral transmission.111 122 133 152 153 158 159 167 168

Advice to Patients

  • Risk for development of inhibitors to factor VIII; importance of informing clinician if usual dosages of factor VIII not able to control bleeding.110 122 134 160 167 179 180 181 182 194 222

  • Risk of transmission of parvovirus B19 and/or hepatitis A from plasma-derived factor VIII products.122 133 152 153 158 167 Importance of informing clinician if symptoms of potential parvovirus B19 infection (e.g., low grade fever, drowsiness, chills, runny nose, rash, arthralgias, arthritis, joint pain) or hepatitis A infection (e.g., low grade fever, anorexia, nausea, vomiting, fatigue, jaundice, dark urine, abdominal pain) occur.122 133 152 153 158 167

  • Importance of discontinuing therapy and immediately informing clinician if hives, urticaria, chest tightness, dyspnea, faintness, hypotension, wheezing, or other manifestations of hypersensitivity reaction or anaphylaxis occur.122 133 152 153 167

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.122 133 152 153 158 167

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.122 133 152 153 158 167

  • Importance of informing patients of other important precautionary information.122 133 152 153 158 167 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Antihemophilic Factor (Human)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV use

number of units indicated on label

Alphanate (solvent/detergent-inactivated; heparin agarose chromatography and selective precipitation purified)

Grifols

Hemofil-M Method M Monoclonal Purified (monoclonal antibody-purified; solvent/detergent-inactivated)

Baxter

Humate-P (heat-treated, wet method; pasteurized)

CSL Behring

Koate-DVI (solvent/detergent-inactivated, heat-treated)

Talecris

Monarc-M Method M Monoclonal Purified (monoclonal antibody-purified; solvent/detergent-inactivated)

Baxter

Monoclate-P (heat-treated, wet method; pasteurized; monoclonal antibody-purified)

CSL Behring

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions February 1, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

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