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 EpisodesType of Bleeding Episode | Factor VIII Level Required (IU/dL or % of normal) | Frequency of Doses (hours) | Duration of Therapy |
---|
Minor |
Early hemarthrosis, minor muscle or oral bleeds. | 20–40 | 12–24 | 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 | 12–24 | 3–4 days or until adequate local hemostasis is achieved. |
Major |
Gastrointestinal bleeding. Intracranial, intra-abdominal, or intrathoracic bleeding. Fractures. | 60–100 | 8–24 | Until 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 Surgery | Factor VIII Level Required (IU/dL or % of normal) | Frequency of Doses (hours) | Duration of Therapy (days) |
---|
Minor |
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 |
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. |
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.
2.3 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.
- 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.