DOSAGE AND ADMINISTRATION
Each vial of RECOMBINATE is labeled with the Factor VIII activity expressed in IU per vial. This potency assignment is referenced to the World Health Organization International Standard for Factor VIII:C Concentrate and is evaluated by appropriate methodology to ensure accuracy of the results.
The expected in vivo peak increase in Factor VIII level expressed as IU/dL of plasma or % (percent) of normal can be estimated by multiplying the dose administered per kg body weight (IU/kg) by two. This calculation is based on the clinical findings of Abildgaard et al
4 and is supported by the data generated by 419 clinical pharmacokinetic studies with RECOMBINATE in 67 patients over time. This pharmacokinetic data demonstrated a peak recovery point above the pre-infusion baseline of approximately 2.0 IU/dL per IU/kg body weight.
Examples (Assuming patient’s baseline Factor VIII level is at <1%):
(1) A dose of 1750 IU RECOMBINATE administered to a 70 kg patient, i.e. 25 IU/kg (1750 IU/70 kg), should be expected to cause a peak post-infusion Factor VIII increase of 25 IU/kg x 2 (IU/dL)/(IU/kg) = 50 IU/dL (50% of normal).
(2) A peak level of 70% is required in a 40 kg child. In this situation, the dose would be 70 IU/dL/[2(IU/dL)/(IU/kg)] x 40 kg = 1400 IU.
Recommended Dosage Schedule
Physician supervision of the dosage is required. The following dosage schedule may be used as a guide.
Degree of hemorrhage
Required peak post infusion Factor VIII activity in the blood (as % of normal or IU/dL plasma)
Frequency of Infusion
|Early hemarthrosis or muscle bleed or oral bleed
||Begin infusion every 12 to 24 hours for one-three days until the bleeding episode is resolved (as indicated by pain), or healing is achieved.
|More extensive hemarthrosis, muscle bleed, or hematoma
||Repeat infusion every 12 to 24 hours for (usually) three days or more until pain and disability are resolved.
|Life threatening bleeds such as head injury, throat bleed, severe abdominal pain
||Repeat infusion every 8 to 24 hours until threat is resolved
Type of Operation
|Minor surgery, including tooth extraction
||A single infusion plus oral antifibrinolytic therapy within one hour is sufficient in approximately 70% of cases.
(pre- and post-operative)
|Repeat infusion every 8 to 24 hours depending on state of healing.
If bleeding is not controlled with the recommended dose, the plasma level of Factor VIII should be determined and a sufficient dose of RECOMBINATE should be administered to achieve a satisfactory clinical response.
The careful control of the substitution therapy is especially important in cases of major surgery or life threatening hemorrhages. In presence of a low titer inhibitor, doses larger than those recommended may be necessary as per standard care.
Although dosage can be estimated by the calculations above, it is strongly recommended that whenever possible, appropriate laboratory tests including serial Factor VIII assays be performed on the patient’s plasma at suitable intervals to assure that adequate Factor VIII levels have been reached and are maintained.
Patients should be evaluated for the development of Factor VIII inhibitors, if the expected plasma Factor VIII activity levels are not attained, or if bleeding is not controlled with an appropriate dose.
Reconstitution: Use Aseptic Technique
- Bring RECOMBINATE (dry factor concentrate) and Sterile Water for Injection, USP, (diluent) to room temperature.
- Remove caps from concentrate and diluent vials.
- Cleanse stoppers with germicidal solution and allow to dry prior to use. Place vials on a flat surface.
- Open the BAXJECT II device package by peeling away the lid, without touching the inside. Do not remove the device from the package.
- Turn the package over. Press straight down to fully insert the clear plastic spike through the diluent vial stopper.
- Grip the BAXJECT II package at its edge and pull the package off the device. Do not remove the blue cap from the BAXJECT II device.Do not touch the exposed white plastic spike.
- Turn the system over, so that the diluent vial is on top. Quickly insert the white plastic spike fully into the RECOMBINATE vial stopper by pushing straight down. The vacuum will draw the diluent into the RECOMBINATE vial.
- Swirl gently until RECOMBINATE is completely dissolved. After reconstitution, the solution should be colorless to faint yellow, and substantially free from foreign particles.
NOTE: Do not refrigerate after reconstitution. (See Administration)
Administration: Use Aseptic Technique
RECOMBINATE is administered by intravenous (IV) injection after reconstitution.
Administer at room temperature.
RECOMBINATE should be administered not more than 3 hours after reconstitution.
Intravenous Syringe Injection
Parenteral drug products should be inspected for particulate matter and discoloration prior to administration, whenever solution and container permit. The solution should be colorless to faint yellow in appearance. If not, do not use the solution and notify Baxter immediately.
Plastic syringes are recommended for use with this product since proteins such as RECOMBINATE tend to stick to the surface of glass syringes.
- Remove the blue cap from the BAXJECT II device. Connect the syringe to the BAXJECT II device. DO NOT INJECT AIR.
- Turn over the connected vials so that the RECOMBINATE vial is on top. Draw the factor concentrate into the syringe by pulling the plunger back slowly.
- Disconnect the syringe; attach a suitable needle and inject intravenously as instructed under Rate of Administration.
- If a patient is to receive more than one vial of RECOMBINATE, the contents of multiple vials may be drawn into the same syringe. Please note that the BAXJECT II device is intended for use with a single vial of RECOMBINATE and Sterile Water for Injection only, therefore reconstituting and withdrawing a second vial into the syringe requires a second BAXJECT II device.
Rate of Administration
The rate of administration should be a rate that ensures the comfort of the patient. Preparations of RECOMBINATE can be administered at a rate of up to 10 mL per minute with no significant reactions when reconstituted with 10 mL sWFI.
The pulse rate should be determined before and during administration of RECOMBINATE. Should a significant increase in pulse rate occur, reducing the rate of administration or temporarily halting the injection usually allows the symptoms to disappear promptly.