(antihemophilic factor [recombinant])

Prescribing Information
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2 DOSAGE AND ADMINISTRATION

2 DOSAGE AND ADMINISTRATION

For intravenous use after reconstitution only.

2.1 Dose

  • 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 % of 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 % of normal) = Total Dose (IU)/body weight (kg) × 2 [IU/dL]/[IU/kg]

On-demand treatment and  Control of Bleeding Episodes

A guide for dosing XYNTHA for on-demand treatment and control of bleeding episodes is provided in Table 1. Maintain the plasma factor VIII activity at or above the levels (in % of normal or in IU/dL) outlined in Table 1 for the indicated period.

Table 1: Dosing for On-demand Treatment and Control of Bleeding Episodes
Type of Bleeding EpisodeFactor VIII Level Required (IU/dL or % of normal)Frequency of Doses
(hours)		Duration of Therapy
Minor
Early hemarthrosis, minor muscle or oral bleeds.20–4012–24At least 1 day, depending upon the severity of the bleeding episode.
Moderate
Bleeding into muscles.
Mild head trauma.
Bleeding into the oral cavity.		30–6012–243–4 days or until adequate local hemostasis is achieved.
Major
Gastrointestinal bleeding.
Intracranial, intra-abdominal, or intrathoracic bleeding.
Fractures.		60–1008–24Until bleeding is resolved.

Perioperative Management

A guide for dosing XYNTHA during surgery (perioperative management) is provided in Table 2. Maintain the plasma factor VIII activity level at or above the level (in % of normal or in IU/dL) outlined in Table 2 for the indicated period. Monitor the replacement therapy by means of plasma factor VIII activity.

Table 2: Dosing for Perioperative Management
Type of SurgeryFactor VIII Level Required (IU/dL or % of normal)Frequency of Doses
(hours)		Duration of Therapy
(days)
Minor
Minor operations, including tooth extraction.30–6012–243–4 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.60–1008–24Until threat is resolved, or in the case of surgery, until adequate local hemostasis and wound healing are achieved.

Routine Prophylaxis

  • Adults and adolescents (≥12 years): The recommended starting regimen is 30 IU/kg of XYNTHA administered 3 times weekly.
  • Children (<12 years): The recommended starting regimen is 25 IU/kg of XYNTHA administered every other day. More frequent or higher doses may be required in children <12 years of age to account for the higher clearance in this age group [see Clinical Pharmacology (12.3)].
  • Adjust the dosing regimen (dose or frequency) based on the patient's clinical response.

2.2 Preparation and Reconstitution

Preparation

  1. Always wash hands before performing the following procedures.
  2. Use aseptic technique during the reconstitution procedures.
  3. Use all components in the reconstitution and administration of this product as soon as possible after opening their sterile containers to minimize unnecessary exposure to the atmosphere.

Note:

  • If the patient uses more than one vial of XYNTHA per infusion, reconstitute each vial according to the following instructions. Remove the diluent syringe, leaving the vial adapter in place. Use a separate 10 milliliter or larger luer lock syringe (not included in this kit) to draw back the reconstituted contents of each vial. Do not detach the diluent syringe or the large luer lock syringe until ready to attach the large luer lock syringe to the next vial adapter.
  • If the patient uses one vial of XYNTHA with one XYNTHA SOLOFUSE® for the infusion, reconstitute the vial and the syringe according to the instructions for each respective product kit. Use a separate 10 milliliter or larger luer lock syringe (not included in this kit) to draw back the reconstituted contents of the vial and the syringe. [see Dosage and Administration (2.4)]

Reconstitution

  1. Allow the XYNTHA vial and the prefilled diluent syringe to reach room temperature.
  2. Remove the plastic flip-top cap from the XYNTHA vial to expose the central portions of the rubber stopper.
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  3. 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 or allow it to touch any surface.
  4. Peel back the cover from the clear plastic vial adapter package. Do not remove the adapter from the package.
  5. Place the XYNTHA vial on a flat surface. While holding the adapter package, place the vial adapter over the XYNTHA vial and press down firmly on the package until the adapter spike penetrates the vial stopper.
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  6. 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.
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  7. 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 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.
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  8. Lift the package away from the adapter and discard the package.
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  9. Place the XYNTHA vial, with the adapter attached, 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.
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  10. Slowly depress the plunger rod to inject all the diluent into the XYNTHA vial.
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  11. Without removing the syringe, gently swirl the contents of the XYNTHA 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, discard the solution and use a new kit.
  12. Invert the XYNTHA vial and slowly draw the solution into the syringe.
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  13. Detach the syringe from the vial adapter by gently pulling and turning the syringe counterclockwise. Discard the empty XYNTHA vial with the adapter attached.

Note:

  • If the solution is not used immediately, carefully replace the syringe cap. Do not touch the syringe tip or the inside of the cap.
  • Store the reconstituted solution at room temperature prior to administration, but use within 3 hours after reconstitution.
  • XYNTHA, 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, including storage time elapsed in a PVC container following reconstitution. The tubing of the infusion set included with this kit does not contain DEHP.

2.3 Administration

For intravenous infusion after reconstitution only.

Inspect the final XYNTHA solution visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The solution should be clear to slightly opalescent and colorless. If it is not, discard the solution and use a new kit.

Use the tubing and the prefilled diluent syringe provided in this kit or a single sterile disposable plastic syringe. Do not administer XYNTHA in the same tubing or container with other medicinal products.

  1. Attach the syringe to the luer end of the infusion set tubing provided.
  2. Apply a tourniquet and prepare the injection site by wiping the skin well with an alcohol swab provided in the kit.
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  3. Remove the protective needle cover and perform venipuncture. Insert the needle on the infusion set tubing into the vein, and remove the tourniquet. Verify proper needle placement.
  4. Inject the reconstituted XYNTHA product intravenously over several minutes. The rate of administration should be determined by the patient's comfort level.
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  5. After infusing XYNTHA, remove and discard the infusion set. The amount of drug product left in the infusion set will not affect treatment.
    Note: Dispose of all unused solution, the empty vial(s), and other used medical supplies in an appropriate container.

2.4 Use of a XYNTHA Vial Kit with a XYNTHA SOLOFUSE Kit

These instructions are for the use of only one XYNTHA Vial Kit with one XYNTHA SOLOFUSE Kit.

  1. Reconstitute the XYNTHA vial using the instructions described in Preparation and Reconstitution [see Dosage and Administration (2.2)].
  2. Detach the empty diluent syringe from the vial adapter by gently turning and pulling the syringe counterclockwise, leaving the contents in the XYNTHA vial with the vial adapter in place.
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  3. Reconstitute the XYNTHA SOLOFUSE using the instructions included with the product kit, remembering to remove most, but not all, of the air from the drug product chamber.
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  4. After removing the protective blue vented cap, connect the XYNTHA SOLOFUSE to the vial adapter by inserting the tip into the adapter opening while firmly pushing and turning the syringe clockwise until secured.
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  5. Slowly depress the plunger rod of the XYNTHA SOLOFUSE until the contents empty into the XYNTHA vial. The plunger rod may move back slightly after release.
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  6. Detach and discard the empty XYNTHA SOLOFUSE from the vial adapter.
    Note: If the syringe turns without detaching from the vial adapter, grasp the white collar and turn.
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  7. Connect a sterile 10 milliliter or larger luer lock syringe to the vial adapter. Inject some air into the vial to make withdrawing the vial contents easier.
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  8. Invert the vial and slowly draw the solution into the large luer lock syringe.
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  9. Detach the syringe from the vial adapter by gently turning and pulling the syringe counterclockwise. Discard the vial with the adapter attached.
  10. Attach the infusion set to the large luer lock syringe as directed [see Dosage and Administration (2.3)].
Medication Guide

FDA-APPROVED PATIENT LABELING

FDA-Approved Patient Labeling

Patient Information

XYNTHA® /ZIN-tha/
[Antihemophilic Factor (Recombinant)]

Please read this patient information carefully before using XYNTHA and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your medical problems or your treatment.

What is XYNTHA?

XYNTHA is an injectable medicine that is used to help control and reduce bleeding in people with hemophilia A. Hemophilia A is also called classic hemophilia. Your healthcare provider may give you XYNTHA when you have surgery.

XYNTHA is not used to treat von Willebrand's disease.

What should I tell my healthcare provider before using XYNTHA?

Tell your healthcare provider about all of your medical conditions, including if you:

  • have any allergies, including allergies to hamsters.
  • are pregnant or planning to become pregnant. It is not known if XYNTHA may harm your unborn baby.
  • are breastfeeding. It is not known if XYNTHA passes into your milk and if it can harm your baby.

Tell your healthcare provider about all of the medicines you take, including all prescription and non-prescription medicines, such as over-the-counter medicines, supplements, or herbal remedies.

How should I infuse XYNTHA?

Step-by-step instructions for infusing with XYNTHA are provided at the end of this leaflet.

The steps listed below are general guidelines for using XYNTHA. Always follow any specific instructions from your healthcare provider. If you are unsure of the procedures, please call your healthcare provider before using.

Call your healthcare provider right away if bleeding is not controlled after using XYNTHA.

Call your healthcare provider right away if you take more than the dose you should take.

Talk to your healthcare provider before traveling. Plan to bring enough XYNTHA for your treatment during this time.

What are the possible side effects of XYNTHA?

Call your healthcare provider or go to the emergency department right away if you have any of the following symptoms because these may be signs of a serious allergic reaction:

  • wheezing
  • difficulty breathing
  • chest tightness
  • turning blue (look at lips and gums)
  • fast heartbeat
  • swelling of the face
  • faintness
  • rash
  • hives

Common side effects of XYNTHA are

  • headache
  • joint pain
  • fever
  • cough
  • vomiting
  • diarrhea
  • weakness

Your body can make antibodies against XYNTHA (called "inhibitors") that may stop XYNTHA from working properly. Your healthcare provider may need to take blood tests from time to time to monitor for inhibitors.

Talk to your healthcare provider about any side effect that bothers you or that does not go away. You may report side effects to FDA at 1-800-FDA-1088.

How should I store XYNTHA?

Store XYNTHA in the refrigerator at 36° to 46°F (2° to 8°C). Store the diluent syringe at 36° to 77°F (2° to 25°C).

Do not freeze.

Protect from light.

XYNTHA can last at room temperature (below 77°F) for up to 3 months. If you store XYNTHA at room temperature, carefully write down the date you put XYNTHA at room temperature, so you will know when to either put it back in the refrigerator, use it immediately, or throw it away. There is a space on the carton for you to write the date.

If stored at room temperature, XYNTHA can be returned one time to the refrigerator until the expiration date. Do not store at room temperature and return it to the refrigerator more than once. Throw away any unused XYNTHA after the expiration date.

Infuse XYNTHA within 3 hours of reconstitution. You can keep the reconstituted solution at room temperature before infusion for up to 3 hours. If you have not used it in 3 hours, throw it away.

Do not use reconstituted XYNTHA if it is not clear to slightly opalescent and colorless.

Dispose of all materials, whether reconstituted or not, in an appropriate medical waste container.

What else should I know about XYNTHA?

Medicines are sometimes prescribed for purposes other than those listed here. Talk to your healthcare provider if you have any concerns. You can ask your healthcare provider for information about XYNTHA that was written for healthcare professionals.

Do not share XYNTHA with other people, even if they have the same symptoms that you have.

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