Xyntha Dosage/Direction for Use

Dosing Considerations: Treatment with Xyntha should be initiated under the supervision of a health professional experienced in the treatment of hemophilia A.
Xyntha is appropriate for use in adults and children including newborns.
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. Individual patients may vary in their response to factor VIII, achieving different levels of in vivo recovery and demonstrating different half-lives. Doses administered should be titrated to the patient's clinical response. In the presence of an inhibitor, higher doses or appropriate alternative treatment may be required. Dosage adjustment for patients with renal or hepatic impairment has not been studied in clinical trials.
The number of units of factor VIII administered is expressed in International Units (IU), which are related to the current World Health Organization (WHO) international standard for factor VIII activity. Factor VIII activity in plasma is expressed either as a percentage (relative to normal human plasma) or in IU (relative to an International Standard for factor VIII in plasma).
One IU of factor VIII activity corresponds approximately to the quantity of factor VIII in one mL 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 2 IU/dL. The required dosage is determined using the following formula: Required units = body weight (kg) x desired factor VIII rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL).
Clinical data support the use of the one-stage clotting assay for monitoring Xyntha therapy.
The labeled potency of Xyntha is based on the European Pharmacopoeia chromogenic substrate assay in which the Pfizer In-House Recombinant Factor VIII Potency Reference Standard has been calibrated using a one-stage clotting assay. This method of potency assignment is intended to harmonize Xyntha with clinical monitoring using a one-stage clotting assay.
Precise monitoring of the replacement therapy by means of plasma factor VIII activity assay should be considered, particularly for surgical intervention.
Recommended Dose and Dosage Adjustment: Dosing for Bleeding and Surgery: In the case of the following hemorrhagic events, consideration should be given to maintaining the factor VIII activity at or above the plasma levels (in % of normal or in IU/dL) for the indicated period, as outlined in the following table. (See Table 6.)

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Dosage for Prophylaxis: Xyntha has been administered prophylactically in a pivotal clinical trial in adolescent and adult previously treated patients at a dose of 30 ± 5 IU/kg given 3 times weekly.
Inhibitors: Patients using factor VIII replacement therapy should be monitored for the development of factor VIII inhibitors. If expected factor VIII activity plasma levels are not attained, or if bleeding is not controlled with an appropriate dose, an assay should be performed to determine if a factor VIII inhibitor is present. In patients with factor VIII inhibitors, factor VIII therapy may not be effective and other therapeutic options should be considered. Management of such patients should be directed by health professionals with experience in the care of patients with hemophilia.
Administration: Patients should follow the specific reconstitution and administration procedures provided by their health professionals. For instructions, patients should follow the recommendations in Administration and Reconstitution (see Cautions for Usage). The procedures as follows are provided as general guidelines for the reconstitution and administration of Xyntha.
Additional instructions are provided after Infusion section that detail the use of a Xyntha vial and a Xyntha Solofuse or multiple Xyntha Solofuse (see Combined Use of a Xyntha Vial Kit and a Xyntha Solofuse, and Multiple Xyntha Solofuse Reconstitution to a 10 cc or Larger Luer Lock Syringe under Cautions for Usage).
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Xyntha Vial Kit: Xyntha is administered by intravenous (IV) infusion after reconstitution of the lyophilized powder with the supplied pre-filled diluent (0.9% Sodium Chloride solution) syringe.
Xyntha Solofuse: Xyntha Solofuse is administered by IV infusion after reconstitution of the freeze-dried powder with the diluent (0.9% Sodium Chloride). Both the Xyntha powder and the diluent are supplied within the prefilled dual-chamber syringe.
Missed Dose: Proceed with the next dose immediately and continue at regular intervals as advised by the health professionals. Do not take a double dose to make up for a forgotten dose.