Antihemophilic Factor

Trade Names:
Advate
- Injection, powder for solution antihemophilic factor (AHF) (recombinant) 250 units
- Injection, powder for solution AHF (recombinant) 500 units
- Injection, powder for solution AHF (recombinant) 1,000 units
- Injection, powder for solution AHF (recombinant) 1,500 units
- Injection, powder for solution AHF (recombinant) 2,000 units
- Injection, powder for solution AHF (recombinant) 3,000 units

Trade Names:
Alphanate
- Injection, lyophilized powder for solution AHF (human) ≥ 5 units/mg of total protein

Trade Names:
Helixate FS
- Injection, lyophilized powder for solution AHF (recombinant) 250 units
- Injection, lyophilized powder for solution AHF (recombinant) 500 units
- Injection, lyophilized powder for solution AHF (recombinant) 1,000 units
- Injection, lyophilized powder for solution AHF (recombinant) 2,000 units

Trade Names:
Hemofil M
- Injection, powder for solution AHF (human) 2 to 20 units/mg of total protein

Trade Names:
Koate-DVI
- Injection, lyophilized powder for solution 250 units AHF (human)
- Injection, lyophilized powder for solution 500 units AHF (human)
- Injection, lyophilized powder for solution 1,000 units AHF (human)

Trade Names:
Kogenate FS
- Injection, lyophilized powder for solution AHF (recombinant) 250 units
- Injection, lyophilized powder for solution AHF (recombinant) 500 units
- Injection, lyophilized powder for solution AHF (recombinant) 1,000 units
- Injection, lyophilized powder for solution AHF (recombinant) 2,000 units

Trade Names:
Monoclate-P
- Injection, lyophilized powder for solution AHF (human) 250 units
- Injection, lyophilized powder for solution AHF (human) 500 units
- Injection, lyophilized powder for solution AHF (human) 1,000 units
- Injection, lyophilized powder for solution AHF (human) 1,500 units

Trade Names:
Recombinate
- Injection, lyophilized powder for solution AHF (recombinant) 250 units
- Injection, lyophilized powder for solution AHF (recombinant) 500 units
- Injection, lyophilized powder for solution AHF (recombinant) 1,000 units

Trade Names:
ReFacto
- Injection, lyophilized powder for solution AHF (recombinant) 250 units
- Injection, lyophilized powder for solution AHF (recombinant) 500 units
- Injection, lyophilized powder for solution AHF (recombinant) 1,000 units
- Injection, lyophilized powder for solution AHF (recombinant) 2,000 units

Trade Names:
Xyntha
- Injection, lyophilized powder for solution AHF (recombinant) 250 units
- Injection, lyophilized powder for solution AHF (recombinant) 500 units
- Injection, lyophilized powder for solution AHF (recombinant) 1,000 units
- Injection, lyophilized powder for solution AHF (recombinant) 2,000 units

Increases factor VIII plasma levels, temporarily correcting the coagulation defect caused by factor VIII deficiency in patients with hemophilia A.

Mean C max is 120 units/dL.

Mean C max at 24 weeks is 109 units/dL.

Mean C max at 12 mo is 2.21 units/mL.

C max at 6 mo is 1.24 units/mL.

Mean steady-state Vd is 0.47 dL/kg.

Mean half-life is approximately 12 h.

Mean half-life at 24 weeks is 14 h.

Mean half-life is 18 h.

Mean half-life is 11.4 h.

Control and prevention of bleeding episodes in patients with hemophilia A; surgical prophylaxis of bleeding in patients with hemophilia A. May be of therapeutic value in patients with factor VIII inhibitors not exceeding 10 Bethesda units (BU)/mL.

For routine prophylactic treatment to reduce the frequency of bleeding episodes and the risk of joint damage in children with no preexisting joint damage.

Short-term prophylaxis to reduce the frequency of spontaneous bleeding episodes.

Hypersensitivity to any component of the product.

Known hypersensitivity to hamster or mouse proteins.

Patients who have manifested life-threatening immediate hypersensitivity reactions, including anaphylaxis.

Known hypersensitivity to mouse proteins.

Known hypersensitivity to bovine, hamster, or mouse proteins.

Known hypersensitivity to hamster proteins.

Dosage and duration of treatment depend on the severity of the factor VIII deficiency, the location and extent of bleeding, and the patient's clinical condition. Titrate administered doses to the patient's response. The required dosage can be determined using the following formula:

AHF units required = body weight (kg) Ч desired factor VIII increase (% normal) Ч 0.5

A peak level of 70% is required in a 40 kg child. See individual product information for dosing guidelines for treatment of hemorrhages and surgical procedures.

IV Administer at least 2 times/wk. In some cases, especially in children, shorter dosage intervals or higher doses may be necessary. In clinical studies, the mean dose/infusion for previously treated patients and previously untreated patients was 29 and 53 units/kg, respectively.

IV 25 units/kg of body weight every other day.

• Dosing and duration of treatment varies based on severity of bleeding and types of surgery. See individual product labeling for more information.
• AHF concentrates may be administered on a regular schedule for prophylaxis of bleeding.
• Administer at room temperature.
• As a general rule, 1 unit of AHF activity per kg will increase the circulating AHF level by 2%.
• Administer at a rate that is comfortable to the patient.
• May administer at a rate of up to 10 mL/min with no significant reactions.

• Kogenate FS
• Kogenate FS is administered by IV injection after reconstitution of lyophilized powder with supplied diluent.
• Administer Kogenate FS within 3 h after reconstitution.
• A dose of Kogenate FS may be administered over a period of 1 to 15 min.

• ReFacto
• ReFacto is administered by IV infusion after reconstitution of the lyophilized powder.
• 1 unit of factor VIII activity corresponds approximately to the quantity of factor VIII in 1 mL of normal human plasma.

• Xyntha
• Xyntha is administered by IV infusion after reconstitution of the freeze-dried powder with supplied pre-filled diluent syringe.
• Do not administer reconstituted Xyntha in the same tubing or container with other medicinal products.
• When reconstituted, contains polysorbate 80, which is known to increase the rate of di-(2-ethylhexy)phthalate (DEHP) extraction from polyvinyl chloride (PVC). Consider this during the preparation and administration of Xyntha , including storage time elapsed in a PVC container following reconstitution.

Store in refrigerator at 36° to 46°F. May be stored at temperatures not exceeding 86°F for 6 mo. Avoid freezing.

Store in refrigerator at 36° to 46°F. Do not freeze. May be stored at temperatures not exceeding 86°F for up to 2 mo.

Store in refrigerator at 36° to 46°F. Alternatively, may be stored at temperatures not exceeding 77°F for up to 3 mo. Do not freeze. Protect from extreme exposure to light.

Store in refrigerator at 36° to 46°F or at temperatures not exceeding 86°F. Avoid freezing. Administer within 3 h of reconstitution.

Store in refrigerator at 36° to 46°F. Store lyophilized powder at temperatures of up to 77°F for up to 6 mo. Avoid freezing. Administer within 3 h of reconstitution.

Store in refrigerator at 36° to 46°F. Alternatively, may be stored at a temperature not exceeding 77°F for up to 6 mo. Avoid freezing.

Store in refrigerator at 36° to 46°F. Alternatively, may be stored at temperatures not exceeding 77°F for up to 3 mo. At the end of 3 mo, the product should be used immediately or discarded. Avoid freezing. Avoid prolonged exposure of vial to light. Reconstituted product may be stored at room temperature prior to administration. Use within 3 h after reconstitution.

Store in refrigerator at 36° to 46°F. Alternatively, may be stored at temperatures not exceeding 77°F for up to 3 mo. The diluent syringe may be stored at 36° to 77°F. Avoid freezing. Avoid prolonged exposure of vial to light.

None well documented.

None well documented.

Slight increase in BP (1%); hypotension (postmarketing).

Hemorrhage (2%); hypotension, vasodilatation (1%); thrombophlebitis of upper arm (postmarketing).

Headache (29%).

Headache, lethargy, somnolence.

Dizziness (2%); depersonalization (1%).

Headache.

Dizziness, headache (4%); asthenia (2%); somnolence (1%); neuropathy (postmarketing).

Headache (24%); asthenia (5%).

Urticaria.

Rash (2%); pruritus (1%); urticaria (postmarketing).

Pruritus, rash, urticaria (16%).

Pruritus (2%); rash, urticaria (1%).

Nasopharyngitis (15%); pharyngolaryngeal pain (11%).

Rhinitis (1%).

Blurred vision.

Taste perversion (3%).

Nausea, vomiting.

Nausea, unusual taste (1%).

Nausea.

Nausea, stomachache.

Nausea (4%); anorexia, diarrhea, GI hemorrhage (1%).

Nausea (9%); diarrhea, vomiting (5%).

UTI (1%).

Decreased coagulation factor VIII, hematoma.

Factor VIII inhibition (15%).

Factor VIII inhibitor (32%); factor VIII AB lab increase (26%); Chinese hamster ovary AB lab increase (17%); mouse immunoglobulin G AB lab increase (12%).

Allergic reaction.

Allergic reactions, anaphylactic reactions (postmarketing).

Anaphylactoid reaction (1%).

Increased AST (1%).

Stinging at infusion site.

Injection-site reactions (2%).

Catheter removal (59%); infusion-site reactions (7%).

Injection-site pain (2%); injection-site reaction (1%).

Arthralgia (23%).

Arthralgia (1%).

Cough (15%).

Dyspnea (postmarketing).

Dyspnea (2%); rhinitis (1%).

Limb injury (35%); pyrexia (17%); accident (15%); fall (13%).

Chills, fever.

Jittery feeling; tingling in the arm, ear, and face.

Central line infection (19%); pyrexia (3%).

Factor VIII inhibitors, mild chills.

Fever (6%); catheter thrombosis, chills, pain (2%); abdominal pain, catheter infection, edema, infection (1%); arm weakness (postmarketing).

Pyrexia (41%).

Identification of clotting defect as factor VIII deficiency is essential before administering AHF. When indicated, monitor plasma factor VIII activity levels by one-stage clotting assay to confirm that adequate factor VIII levels have been achieved and are maintained.

Determine pulse rate before and during administration. If a sufficient increase occurs, reducing the rate of administration or temporarily halting the injection usually allows the symptoms to disappear promptly.

Monitor patients for development of factor VIII inhibitors.

Category C .

Undetermined.

Studies in previously treated patients younger than 6 yr of age are currently ongoing. A least 54 subjects younger than 16 yr of age have been treated with Advate in phase 2/3 studies.

Safety and efficacy not established in children younger than 16 yr of age.

Appropriate for use in children of all ages, including neonates.

Safety and efficacy not established in children.

Safety and efficacy have been demonstrated in 33 children; as in adults, base dosing upon weight.

Studies did not include subjects 65 yr of age and older. Use with caution. Individualize dose selection.

Allergic-type hypersensitivity (including anaphylaxis) reactions may occur.

Hemofil M and Monoclate-P contain trace amounts of mouse proteins; therefore, patients may develop hypersensitivity to these proteins. Advate , Helixate FS , Kogenate FS , and ReFacto contain trace amounts of mouse and hamster proteins; therefore, patients may develop hypersensitivity to these proteins. Xyntha contains trace amounts of hamster proteins; therefore, patients may develop hypersensitivity to these proteins. Recombinate contains trace amounts of bovine, hamster, and mouse proteins; therefore, patients may develop hypersensitivity to these proteins.

When large or frequently repeated doses are needed in patients of blood group A, B, or AB, intravascular hemolysis may occur; monitor the hematocrit and direct Coombs tests.

Alphanate , Hemofil M , Koate-DVI , and Monoclate-P are made from human blood, which may contain infectious agents, such as viruses, that can cause disease.

Certain components used in packaging contain dry natural latex rubber that may cause allergic reactions in latex-sensitive individuals.

Neutralizing antibodies (inhibitors) of factor VIII may occur in patients with hemophilia A. Inhibitor titers above 10 BU/mL are likely to make control of hemostasis with AHF concentrates either impossible or impractical because of the large doses required. Alternative means of treating or preventing bleeding may be required.

Some viruses, such as parvovirus B19 or hepatitis A, are particularly difficult to remove or inactivate at this time and may seriously affect seronegative pregnant women or immunocompromised individuals.

Not effective in controlling the bleeding of patients with von Willebrand disease.

Massive doses have rarely resulted in acute hemolytic anemia, hyperfibrinogenemia, or increased bleeding tendency.

No symptoms of overdose have been reported.

• Instruct patients to discontinue use and contact health care provider if early signs or symptoms of hypersensitivity or anaphylaxis (including generalized urticaria, hypotension, rash with itching, tightness of the chest, and wheezing) occur.
• Advise patients that some viruses, such as parvovirus B19 or hepatitis A, are particularly difficult to remove or inactivate at this time and may seriously affect seronegative pregnant women or immunocompromised individuals.
• Advise patients to contact health care provider if they experience a lack of clinical response to factor VIII replacement therapy because this may be a manifestation of an inhibitor.
• Advise patients to bring an adequate supply of agent for anticipated treatment when traveling and to consult health care provider before traveling.

Comments for Antihemophilic Factor