Recommended Topic Related To:

Xyntha

"The U.S. Food and Drug Administration today approved Eloctate, Antihemophilic Factor (Recombinant), Fc fusion protein, for use in adults and children who have Hemophilia A. Eloctate is the first Hemophilia A treatment designed to require less fre"...

Xyntha

Indications
Dosage
How Supplied

INDICATIONS

Control of Bleeding Episodes in Hemophilia A

XYNTHA Antihemophilic Factor (Recombinant), Plasma/Albumin-Free is indicated for the control and prevention of bleeding episodes in patients with hemophilia A (congenital factor VIII deficiency or classic hemophilia).

XYNTHA (antihemophilic factor) does not contain von Willebrand factor and, therefore, is not indicated in von Willebrand's disease.

Surgical Prophylaxis in Patients with Hemophilia A

XYNTHA Antihemophilic Factor (Recombinant), Plasma/Albumin-Free is indicated for surgical prophylaxis in patients with hemophilia A.

DOSAGE AND ADMINISTRATION

Treatment with XYNTHA Antihemophilic Factor (Recombinant), Plasma/Albumin-Free should be initiated 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. Doses administered should be titrated to the patient's clinical response. In the presence of an inhibitor, higher doses may be required.1

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 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)

The labeled potency of XYNTHA (antihemophilic factor) is based on the European Pharmacopoeia chromogenic substrate assay, in which the Wyeth manufacturing standard has been calibrated using a one- stage clotting assay. This method of potency assignment is intended to harmonize XYNTHA (antihemophilic factor) with clinical monitoring using a one-stage clotting assay. [see CLINICAL PHARMACOLOGY]

Control of Bleeding Episodes

In the case of the following bleeding events, consideration should be given to maintaining the factor VIII activity at or above the plasma levels (in % of normal or in IU/dL) outlined below for the indicated period.

Type of Bleeding Episode Factor VIII
Level Required
(IU/dL or % of normal)
Frequency of Doses /
Duration of Therapy
Minor
Early hemarthrosis, minor muscle or oral bleeds.
20-40
Repeat every 12-24 hours as necessary until resolved. At least 1 day, depending upon the severity of the bleeding episode.
Moderate
Bleeding into muscles. Mild head trauma. Bleeding into the oral cavity.
30-60
Repeat infusion every 12-24 hours for 3-4 days or until adequate local hemostasis is achieved.
Major
Gastrointestinal bleeding. Intracranial, intra-abdominal or intrathoracic bleeding. Fractures.
60-100
Repeat infusion every 8-24 hours until bleeding is resolved.

Surgical Prophylaxis in Patients with Hemophilia A

In the case of the following bleeding events, consideration should be given to maintaining the factor VIII activity at or above the plasma levels (in % of normal or in IU/dL) outlined below for the indicated period. Monitoring of replacement therapy by means of plasma factor VIII activity is recommended, particularly for surgical intervention.

The following chart can be used to guide dosing in surgery:

Type of Bleeding Episode Factor VIII
Level Required
(IU/dL or % of normal)
Frequency of Doses /
Duration of Therapy
Minor
Minor operations, including tooth extraction.
30-60
Repeat infusion every 12-24 hours for 3-4 days or until adequate local hemostasis is achieved. For tooth extraction, a single infusion plus oral antifibrinolytic therapy within 1 hour may be sufficient.
Major
Major operations.
60-100
Repeat infusion every 8-24 hours until threat is resolved, or in the case of surgery, until adequate local hemostasis and wound healing are achieved.

Instructions for Use

XYNTHA (antihemophilic factor) is administered by intravenous (IV) infusion after reconstitution of the freeze-dried powder with the supplied pre-filled diluent (0.9% Sodium Chloride solution) syringe.

Patients should follow the specific reconstitution and administration procedures provided by their physicians. For instructions, patients should follow the recommendations in the FDA-Approved Patient Labeling . The procedures below are provided as general guidelines for the reconstitution and administration of XYNTHA (antihemophilic factor) .

Preparation and Reconstitution

Preparation
  1. Always wash your hands before performing the following procedures.
  2. Aseptic technique (meaning clean and germ-free) should be used during the reconstitution procedure.
  3. All components used in the reconstitution and administration of this product should be used as soon as possible after opening their sterile containers to minimize unnecessary exposure to the atmosphere.

Note: If you use more than one vial of XYNTHA (antihemophilic factor) per infusion, each vial should be reconstituted according to the following instructions. The diluent syringe should be removed, leaving the vial adapter in place, and a separate large luer lock syringe may be used to draw back the reconstituted contents of each vial. Do not detach the diluent syringes or the large luer lock syringe until you are ready to attach the large luer lock syringe to the next vial adapter.

Reconstitution
  1. Allow the vials of freeze-dried XYNTHA (antihemophilic factor) and the pre-filled diluent syringe to reach room temperature.
  2. Remove the plastic flip-top cap from the XYNTHA (antihemophilic factor) vial to expose the central portions of the rubber stopper.
  3. Reconstitution - illustration 1

  4. Wipe the top of the vial with the alcohol swab provided, or use another antiseptic solution, and allow to dry. After cleaning, do not touch the rubber stopper with your hand or allow it to touch any surface.
  5. Peel back the cover from the clear plastic vial adapter package. Do not remove the adapter from the package.
  6. Place the vial on a flat surface. While holding the adapter package, place the vial adapter over the vial and press down firmly on the package until the adapter spike penetrates the vial stopper.
  7. Reconstitution - illustration 2

  8. Grasp the plunger rod as shown in the diagram. Avoid contact with the shaft of the plunger rod. Attach the threaded end of the plunger rod to the diluent syringe plunger by pushing and turning firmly.
  9. Reconstitution - illustration 3

  10. Break off the tamper-resistant plastic tip cap from the diluent syringe by snapping the perforation of the cap. Do not touch the inside of the cap or the syringe tip. The diluent syringe may need to be recapped (if not administering reconstituted XYNTHA (antihemophilic factor) immediately), so place the cap on its top on a clean surface in a spot where it would be least likely to become environmentally contaminated.
  11. Reconstitution - illustration 4

  12. Lift the package away from the adapter and discard the package.
  13. Reconstitution - illustration 5

  14. Place the vial on a flat surface. Connect the diluent syringe to the vial adapter by inserting the tip into the adapter opening while firmly pushing and turning the syringe clockwise until secured.
  15. Reconstitution - illustration 6

  16. Slowly depress the plunger rod to inject all the diluent into the XYNTHA (antihemophilic factor) vial.
  17. Reconstitution - illustration 7

  18. Without removing the syringe, gently swirl the contents of the vial until the powder is dissolved.
    Note: The final solution should be inspected visually for particulate matter before administration. The solution should be clear to slightly opalescent and colorless. If it is not, the solution should be discarded and a new kit should be used.
  19. Invert the vial and slowly draw the solution into the syringe.
  20. Reconstitution - illustration 8

  21. Detach the syringe from the vial adapter by gently pulling and turning the syringe counter-clockwise. Discard the vial with the adapter attached.

Note: If the solution is not to be used immediately, the syringe cap should be carefully replaced. Do not touch the syringe tip or the inside of the cap.

The reconstituted solution may be stored at room temperature prior to administration, but should be administered within 3 hours.

XYNTHA (antihemophilic factor) , when reconstituted, contains polysorbate 80, which is known to increase the rate of di-(2-ethylhexyl)phthalate (DEHP) extraction from polyvinyl chloride (PVC). This should be considered during the preparation and administration of XYNTHA (antihemophilic factor) , including storage time elapsed in a PVC container following reconstitution. It is important that the recommendations in Dosage and Administration (2) be followed closely.

Administration

XYNTHA (antihemophilic factor) is administered by intravenous (IV) infusion after reconstitution with the supplied pre-filled diluent (0.9% Sodium Chloride solution, 4 mL) syringe. Parenteral drug products should be inspected for particulate matter and discoloration prior to administration, whenever solution and container permit.

XYNTHA (antihemophilic factor) should be administered using the tubing provided in this kit and the pre-filled diluent syringe provided, or a single sterile disposable plastic syringe. In addition, the solution should be withdrawn from the vial using the vial adapter.

  1. Attach the syringe to the luer end of the infusion set tubing provided.
  2. Apply a tourniquet and prepare the injections site by wiping the skin well with an alcohol swab provided in the kit.
  3. Administration - illustration 1

  4. Perform venipuncture. Insert the needle on the infusion set tubing into the vein, and remove the tourniquet. The reconstituted XYNTHA (antihemophilic factor) product should be injected intravenously over several minutes. The rate of administration should be determined by the patient's comfort level.
  5. Administration - illustration 1

Reconstituted XYNTHA (antihemophilic factor) should not be administered in the same tubing or container with other medicinal products.3

Following completion of XYNTHA (antihemophilic factor) treatment, remove the infusion set and discard. Dispose of all unused solution, the empty vial(s), and the used needles and syringes in an appropriate container for throwing away waste that might hurt others if not handled properly.

HOW SUPPLIED

Dosage Forms And Strengths

XYNTHA (antihemophilic factor) is supplied as a white to off-white powder in the following dosages:

  • 250 IU
  • 500 IU
  • 1000 IU
  • 2000 IU

XYNTHA™ Antihemophilic Factor (Recombinant), Plasma/Albumin-Free is supplied in kits that include single-use (Freeze-Dried) vials that contain nominally 250, 500, 1000, or 2000 IU per vial:

250 IU Kit: NDC 58394-012-01
500 IU Kit: NDC 58394-013-01
1000 IU Kit: NDC 58394-014-01
2000 IU Kit: NDC 58394-015-01

Actual factor VIII activity in IU is stated on the label of each XYNTHA Antihemophilic Factor (Recombinant), Plasma/Albumin-Free vial.

In addition, each XYNTHA Antihemophilic Factor (Recombinant), Plasma/Albumin-Free kit contains: one pre-filled diluent syringe containing 4 mL 0.9% Sodium Chloride with plunger rod for assembly, one vial adapter, one sterile infusion set, two alcohol swabs, one bandage, one gauze, and one package insert.

Storage and Handling

Product as packaged for sale: XYNTHA Antihemophilic Factor (Recombinant), Plasma/Albumin-Free should be stored under refrigeration at a temperature of 2° to 8°C (36° to 46°F). XYNTHA (antihemophilic factor) may also be stored at room temperature not to exceed 25°C (77°F) for up to 3 months, until the expiration date. The patient should write in the space provided on the outer carton the date the product was placed at room temperature. At the end of the 3-month period, the product should not be put back into the refrigerator, but should be used immediately or discarded. The diluent syringe may be stored at 2° to 25°C (36° to 77°F). Freezing should be avoided to prevent damage to the pre-filled diluent syringe. During storage, avoid prolonged exposure of XYNTHA (antihemophilic factor) vial to light. Do not use XYNTHA (antihemophilic factor) after the expiration date on the label.

Product after reconstitution: The reconstituted solution may be stored at room temperature prior to administration. The product does not contain a preservative and should be used within 3 hours.

REFERENCES

1. Nilsson IM, Berntorp EE and Freiburghaus C. Treatment of patients with factor VIII and IX inhibitors. Thromb Haemost. 1993;70(1):56-59.

2.   Hoyer LW. Hemophilia A. N Engl J Med. 1994;330:38-47.

3.   Juhlin F. Stability and Compatibility of Reconstituted Recombinant Factor VIII SQ, 250 IU/ml, in a System for Continuous Infusion. Pharmacia Document 9610224, 1996.

Wyeth Pharmaceuticals Inc. Philadelphia, PA 19101. FDA Rev date: n/a

Last reviewed on RxList: 3/18/2008
This monograph has been modified to include the generic and brand name in many instances.

Indications
Dosage
How Supplied
A A A

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


Women's Health

Find out what women really need.