20 to 40 IU per kg every other day (3 to 4 times weekly).
•
Alternatively, use every third day dosing regimen targeted to maintain FVIII trough levels ≥ 1%.
DOSAGE FORMS AND STRENGTHS
ADVATE is available as a lyophilized powder in single-use vials containing nominally 250, 500, 1000, 1500, 2000, 3000 or 4000 IU. (3) CONTRAINDICATIONS
Do not use in patients who have life-threatening hypersensitivity reactions, including anaphylaxis, to mouse or hamster protein or other constituents of the product (mannitol, trehalose, sodium chloride, histidine, Tris, calcium chloride, polysorbate 80, and/or glutathione). (4) WARNINGS AND PRECAUTIONS
•
Hypersensitivity reactions including anaphylaxis may occur. Patients may develop hypersensitivity to mouse or hamster protein, which is present in trace amounts in the product. Should symptoms occur, discontinue treatment with ADVATE and administer appropriate treatment. ( 5.1)
•
Development of activity-neutralizing antibodies may occur. If expected plasma factor VIII activity levels are not attained, or if bleeding is not controlled with an appropriate dose, perform an assay that measures factor VIII inhibitor concentration. ( 5.2, 5.3)
ADVERSE REACTIONS
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Serious adverse drug reactions reported are hypersensitivity and factor VIII inhibitors. (6.1)
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The most common adverse drug reactions observed in greater than 5% of patients are pyrexia, headache, cough, and nasopharyngitis, arthralgia, vomiting, upper respiratory tract infection, limb injury, nasal congestion and diarrhea. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Baxter Healthcare Corporation at 1-866-888-2472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch (6)
USE IN SPECIFIC POPULATIONS
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Pregnancy: No human or animal data. Use only if clearly needed. ( 8.1)
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Pediatric Use: Clearance (based on per kg body weight) is higher in the pediatric population. Dose adjustment may be needed. ( 8.4)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Sections or subsections omitted from the full prescribing information are not listed.
1 INDICATIONS AND USAGE
ADVATE [Antihemophilic Factor (Recombinant)] is a recombinant antihemophilic factor indicated for use in children and adults with hemophilia A (congenital factor VIII deficiency) for:
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Control and prevention of bleeding episodes.
•
Perioperative management.
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Routine prophylaxis to prevent or reduce the frequency of bleeding episodes.
ADVATE is not indicated for the treatment of von Willebrand disease.
2 DOSAGE AND ADMINISTRATION
For intravenous injection after reconstitution only.
2.1 Dose
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Dosage and duration of treatment depend on the severity of factor VIII deficiency, the location and extent of the bleeding, and the patient’s clinical condition. Careful control of replacement therapy is especially important in cases of major surgery or life-threatening bleeding episodes.
•
Each vial of ADVATE has the recombinant factor VIII potency in International Units (IU) stated on the label. The expected in vivo peak increase in factor VIII level expressed as IU/dL of plasma or percent of normal can be estimated using the following formulas:
IU/dL (or % of normal) = [total dose (IU)/body weight (kg)] x 2 [IU/dL]/[IU/kg]
OR
Required dose (International Units) = body weight (kg) x desired factor VIII rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL)
Examples (assuming patient's baseline factor VIII level is < 1% of normal):
1.
A dose of 1750 IU ADVATE administered to a 70 kg patient should be expected to result in a peak post-infusion factor VIII increase of 1750 IU × {[2 IU/dL]/[IU/kg]}/[70 kg] = 50 IU/dL (50% of normal).
2.
A peak level of 70% is required in a 40 kg child. In this situation, the appropriate dose would be 40 kg × 70 IU/dL/{[2 IU/dL]/[IU/kg]} = 1400 IU.
•
Base the dose and frequency on the individual clinical response. Patients may vary in their pharmacokinetic (e.g., half-life, in vivo recovery) and clinical responses to ADVATE. Although the dose can be estimated by the calculations above, whenever possible, perform appropriate laboratory tests including serial factor VIII activity assays. [see Warnings and Precautions (5.3) and Clinical Pharmacology ( 12.3)]
Control and Prevention of Bleeding Episodes
A guide for dosing ADVATE for the control and prevention of bleeding episodes is provided in
