Xyntha

/ Pfizer

Treatment with Xyntha should be initiated under the supervision of a physician 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
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.
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.

Maintenance of Factor VIII Activity for Various Hemorrhagic Events: See prescribing information for full details.
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 physicians with experience in the care of patients with hemophilia.
Administration
Patients should follow the specific reconstitution and administration procedures provided by their
physicians. For instructions- See prescribing information for full details.

Treatment and prophylaxis of bleeding in patients with hemophilia A (congenital factor VIII deficiency).

XYNTHA is contraindicated in patients who have manifested life-threatening immediate hypersensitivity reactions, including anaphylaxis, to the product or its components, including hamster proteins.

Hypersensitivity Reactions
Allergic-type hypersensitivity reactions, including anaphylaxis, are possible with XYNTHA. Inform patients of the early signs or symptoms of hypersensitivity reactions (including hives [rash with itching], generalized urticaria, chest tightness, wheezing, and hypotension) and anaphylaxis. Discontinue XYNTHA if hypersensitivity symptoms occur and administer appropriate emergency treatment.
XYNTHA contains trace amounts of hamster proteins. Patients treated with this product may develop hypersensitivity to these non-human mammalian proteins.

The most common adverse reactions (≥10%) with XYNTHA in adult and pediatric previously treated patients (PTPs) were headache, arthralgia, pyrexia, and cough.See prescribing information for full details.

Pregnancy: It is not known whether XYNTHA can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.
Lactation: There is no information regarding the presence of XYNTHA in human milk, the effect on the breastfed infant, or the effects on milk production.
See prescribing information for full details.         

Compatibility: In the absence of incompatibility studies, this drug in reconstituted  form should not be administered in the same tubing or container with other medicinal products.
Storage: Antihemophilic Factor (Recombinant), Plasma/Albumin-Free should be stored under refrigeration at a temperature of 2°C to 8°C.