2 DOSAGE AND ADMINISTRATION
For intravenous use after reconstitution only.
- 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)
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.
|Type of Bleeding Episode||Factor VIII Level Required (IU/dL or % of normal)||Frequency of Doses|
|Duration of Therapy|
|Early hemarthrosis, minor muscle or oral bleeds.||20–40||12–24||At least 1 day, depending upon the severity of the bleeding episode.|
|Bleeding into muscles.|
Mild head trauma.
Bleeding into the oral cavity.
|30–60||12–24||3–4 days or until adequate local hemostasis is achieved.|
Intracranial, intra-abdominal, or intrathoracic bleeding.
|60–100||8–24||Until bleeding is resolved.|
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.
|Type of Surgery||Factor VIII Level Required (IU/dL or % of normal)||Frequency of Doses|
|Duration of Therapy|
|Minor operations, including tooth extraction.||30–60||12–24||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 operations.||60–100||8–24||Until threat is resolved, or in the case of surgery, until adequate local hemostasis and wound healing are achieved.|
- 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
- Always wash hands before performing the following procedures.
- Use aseptic technique during the reconstitution procedures.
- 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.
- 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)]
- Allow the XYNTHA vial and the prefilled diluent syringe to reach room temperature.
- Remove the plastic flip-top cap from the XYNTHA vial to expose the central portions of the rubber stopper.
- 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.
- Peel back the cover from the clear plastic vial adapter package. Do not remove the adapter from the package.
- 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.
- 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.
- 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.
- Lift the package away from the adapter and discard the package.
- 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.
- Slowly depress the plunger rod to inject all the diluent into the XYNTHA vial.
- 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.
- Invert the XYNTHA vial and slowly draw the solution into the syringe.
- Detach the syringe from the vial adapter by gently pulling and turning the syringe counterclockwise. Discard the empty XYNTHA vial with the adapter attached.
- 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.
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.
- Attach the syringe to the luer end of the infusion set tubing provided.
- Apply a tourniquet and prepare the injection site by wiping the skin well with an alcohol swab provided in the kit.
- 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.
- Inject the reconstituted XYNTHA product intravenously over several minutes. The rate of administration should be determined by the patient's comfort level.
- 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.
- Reconstitute the XYNTHA vial using the instructions described in Preparation and Reconstitution [see Dosage and Administration (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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Invert the vial and slowly draw the solution into the large luer lock syringe.
- Detach the syringe from the vial adapter by gently turning and pulling the syringe counterclockwise. Discard the vial with the adapter attached.
- Attach the infusion set to the large luer lock syringe as directed [see Dosage and Administration (2.3)].