XYNTHA- antihemophilic factor (recombinant)
Wyeth BioPharma Division of Wyeth Pharmaceuticals Inc., a subsidiary of Pfizer Inc.
1 INDICATIONS AND USAGE
XYNTHA, Antihemophilic Factor (Recombinant), is indicated for use in adults and children with hemophilia A (congenital factor VIII deficiency) for:
Control and prevention of bleeding episodes
Perioperative management
XYNTHA does not contain von Willebrand factor, and therefore is not indicated in patients with von Willebrand's disease.
2 DOSAGE AND ADMINISTRATION
For intravenous use after reconstitution only.
2.1 Dose
Initiate treatment with XYNTHA under the supervision of a physician experienced in the treatment of hemophilia A.
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 the administered doses to the patient's clinical response.
One International Unit (IU) of factor VIII activity corresponds approximately to the quantity of factor VIII in one milliliter of normal human plasma. The calculation of the required dosage of factor VIII is based upon the empirical finding that, on average, 1 IU of factor VIII per kg body weight raises the plasma factor VIII activity by approximately 2 IU/dL.2
The expected in vivo peak increase in factor VIII level expressed as IU/dL (or % normal) can be estimated using the following formulas:
Dosage (International Units) = body weight (kg) � desired factor VIII rise (IU/dL or % of normal) � 0.5 (IU/kg per IU/dL)
or
IU/dL (or % normal) = Total Dose (IU)/body weight (kg) � 2 [IU/dL]/[IU/kg]
DESCRIPTION
The active ingredient in XYNTHA, Antihemophilic Factor (Recombinant), is a recombinant antihemophilic factor (rAHF), also called coagulation factor VIII, which is produced by recombinant DNA technology. It is secreted by a genetically engineered Chinese hamster ovary (CHO) cell line. The cell line is grown in a chemically defined cell culture medium that contains recombinant insulin, but does not contain any materials derived from human or animal sources.
The rAHF in XYNTHA is a purified glycoprotein, with an approximate molecular mass of 170 kDa consisting of 1,438 amino acids, which does not contain the B-domain.13 The amino acid sequence of the rAHF is comparable to the 90 + 80 kDa form of human coagulation factor VIII.
The purification process uses a series of chromatography steps, one of which is based on affinity chromatography using a patented synthetic peptide affinity ligand.14 The process also includes a solvent-detergent viral inactivation step and a virus-retaining nanofiltration step.
The potency expressed in International Units (IU) is determined using the chromogenic assay of the European Pharmacopoeia. The Wyeth manufacturing reference standard for potency has been calibrated against the World Health Organization (WHO) International Standard for factor VIII activity using the one-stage clotting assay. The specific activity of XYNTHA is 5,500 to 9,900 IU per milligram of protein.
XYNTHA is formulated as a sterile, nonpyrogenic, no preservative, lyophilized powder preparation for intravenous injection. Each single-use prefilled dual-chamber syringe (named XYNTHA SOLOFUSE) contains nominally 250, 500, 1000, 2000, or 3000 IU of XYNTHA. Upon reconstitution, the product is a clear to slightly opalescent, colorless solution that contains sodium chloride, sucrose, L-histidine, calcium chloride and polysorbate 80.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
XYNTHA temporarily replaces the missing clotting factor VIII that is needed for effective hemostasis.
12.2 Pharmacodynamics
The activated partial thromboplastin time (aPTT) is prolonged in patients with hemophilia. Determination of aPTT is a conventional in vitro assay for biological activity of factor VIII. Treatment with XYNTHA normalizes the aPTT over the effective dosing period.
