Xyntha Dosage/Direction for Use

For intravenous use after reconstitution only.
Dose: Initiate treatment with XYNTHA 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. 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.
The expected in vivo peak increase in factor VIII level expressed as IU/dL (or % of normal) can be estimated using the following formulas: (See Equation 1.)

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or; (See Equation 2.)

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Control and Prevention of Bleeding Episodes: A guide for dosing XYNTHA for the control and prevention of bleeding episodes is provided in Table 6. Maintain the plasma factor VIII activity at or above the plasma levels (in % of normal or in IU/dL) outlined in Table 6 for the indicated period. (See Table 6.)

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Perioperative Management: A guide for dosing XYNTHA during surgery (perioperative management) is provided in Table 7. Maintain the plasma factor VIII activity level at or above the level (in % of normal or in IU/dL) outlined in Table 7 for the indicated period. Monitor the replacement therapy by means of plasma factor VIII activity. (See Table 7.)

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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 Pharmacology: Pharmacokinetics under Actions].
Adjust the dosing regimen (dose or frequency) based on the patient's clinical response.
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 [see Dosage & Administration].
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.
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.
6. Grasp the plunger rod. 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.
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.
8. Lift the package away from the adapter and discard the package.
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.
10. Slowly depress the plunger rod to inject all the diluent into the XYNTHA vial.
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.
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.
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.
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.
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.