Advate Dosage

Generic name: antihemophilic factor, human recombinant
Dosage form: injection

The information at Drugs.com is not a substitute for medical advice. ALWAYS consult your doctor or pharmacist.

For Intravenous Use After Reconstitution only

  • Treatment with ADVATE should be initiated under the supervision of a physician experienced in the treatment of hemophilia A.
  • Each vial of ADVATE has the recombinant Factor VIII potency in international units stated on the label. The expected in vivo peak increase in Factor VIII level expressed as IU/dL of plasma or percent normal can be estimated by multiplying the dose administered per kg body weight (IU/kg) by 2.
  • The dosage and duration depend on the severity of Factor VIII deficiency, the location and extent of the bleeding, and the patient's clinical condition. Careful control of replacement therapy is especially important in cases of major surgery or life-threatening bleeding episodes. [Control and Prevention of Bleeding Episodes (2.1) and Perioperative Management (2.2)]

The expected in vivo peak increase in Factor VIII level expressed as IU/dL (or % of normal) can be estimated using the following formulas:

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

OR

Dose (IU) = body weight (kg) × Desired Factor VIII Rise (IU/dL or % of normal) × 0.5 (IU/kg per IU/dL)

Examples (assuming patient's baseline Factor VIII level is < 1% of normal):

  1. A dose of 1750 IU ADVATE administered to a 70 kg patient should be expected to result in a peak post-infusion Factor VIII increase of 1750 IU × {[2 IU/dL]/[IU/kg]}/[70 kg] = 50 IU/dL (50% of normal).
  2. A peak level of 70% is required in a 40 kg child. In this situation, the appropriate dose would be 40 kg × 70 IU/dL/{[2 IU/dL]/[IU/kg]} = 1400 IU.

The dose and frequency of administration should be based on the individual clinical response. Patients may vary in their pharmacokinetic (e.g. half-life, in vivo recovery) and clinical responses to ADVATE. Although you can estimate the dose by the calculations above, it is highly recommended that, whenever possible, appropriate laboratory tests including serial Factor VIII activity assays be performed  [see WARNINGS and PRECAUTIONS: Monitoring Laboratory Tests (5.4) and Pharmacokinetics (12.3)].

Control and Prevention of Bleeding Episodes

A guide for dosing in the treatment of bleeding episodes is provided in Table 1. The careful control of treatment dose is especially important in cases of life-threatening episodes.

Table 1 Guide to ADVATE Dosing for Treatment of Bleeding Episodes in Adults and Children
*
Dose (IU/kg) = Desired Factor VIII Rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL)
Degree of Hemorrhage
Or
Type of Bleeding Episodes
Required Peak Post-infusion Factor VIII Activity in the Blood
(as % of Normal or IU/dL)
Dosage and Frequency Necessary to Maintain the Therapeutic Plasma Level
Minor
Early hemarthrosis, mild muscle bleeding, or mild oral bleeding episode.
20-40 10-20 IU/kg* Repeat infusions every 12 to 24 hours (8 to 24 hours for patients under the age of 6) for one to three days until the bleeding episode is resolved (as indicated by relief of pain) or healing is achieved.
Moderate
Moderate bleeding into muscles, bleeding into the oral cavity, definite hemarthroses, and known trauma.
30-60 15-30 IU per kg* Repeat infusions every 12 to 24 hours (8 to 24 hours for patients under the age of 6) for three days or more until the bleeding episode is resolved (as indicated by relief of pain) or healing is achieved.
Major
Significant gastrointestinal bleeding, intracranial, intra-abdominal or intrathoracic bleeding, central nervous system bleeding, bleeding in the retropharyngeal or retroperitoneal spaces or iliopsoas sheath, Fractures, Head trauma.
60-100 Initial dose 30-50 IU per kg:
Repeat dose 30-50 IU per kg every 8 to 24 hours (6 to 12 hours for patients under the age of 6) until resolution of the bleeding episode has occurred.

Peri-operative Management

A guide for dosing in perioperative management is provided in Table 2. The careful control of dose and duration of treatment is especially important in cases of major surgery or life-threatening bleeding episodes.

Table 2 Guide to ADVATE Dosing for Perioperative Management in Adults and Children
Type of Surgery Required Peak Post-infusion Factor VIII Activity in the Blood
(% of Normal or IU/dL)
Frequency of Infusion
*
Dose (IU/kg) = Desired Factor VIII Rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL)

Minor

Including tooth extraction

60-100 A single bolus infusion (30-50 IU/kg*) beginning within one hour of the operation. Optional additional dosing every 12 to 24 hours as needed to control bleeding. For dental procedures, adjunctive therapy may be considered.

Major

Examples include intracranial, Intra-abdominal, or Intrathoracic surgery, joint replacement surgery

80-120
(pre- and post-operative)
Preoperative bolus infusion: 40-60 IU/kg*. Verify 100% activity has been achieved prior to surgery. Maintenance bolus infusion (40-60 IU/kg*) repeat infusions every 8 to 24 hours (6 to 24 hours for patients under the age of 6), depending on the desired level of Factor VIII and state of wound healing.

Instruction for Use

ADVATE is administered by intravenous (IV) injection after reconstitution. Patients should follow the specific reconstitution and administration procedures provided by their physicians.

For instructions, patients should follow the recommendations in the FDA-approved patient labeling.

Reconstitution, product administration, and handling of the administration set and needles must be done with caution. Percutaneous puncture with a needle contaminated with blood can transmit infectious viruses including HIV (AIDS) and hepatitis. Obtain immediate medical attention if injury occurs. Place needles in a sharps container after single use. Discard all equipment, including any reconstituted ADVATE in an appropriate container.

Preparation and Reconstitution:

The procedures below are provided as general guidelines for the reconstitution and administration of ADVATE. Always work on a clean surface and wash your hands before performing the following procedures.

  1. Bring the ADVATE (dry factor concentrate) and Sterile Water for Injection, USP (diluent) to room temperature.
  2. Remove caps from the factor concentrate and diluent vials.
  3. Cleanse stoppers with germicidal solution, and allow to dry prior to use. Place the vials on a flat surface.
  4. Open the BAXJECT II device package by peeling away the lid, without touching the inside (Figure A). Do not remove the device from the package.
  5. Turn the package over. Press straight down to fully insert the clear plastic spike through the diluent vial stopper (Figure B).
  6. Grip the BAXJECT II package at its edge and pull the package off the device (Figure C). Do not remove the blue cap from the BAXJECT II device. Do not touch the exposed white plastic spike.
  7. Turn the system over, so that the diluent vial is on top. Quickly insert the white plastic spike fully into the ADVATE vial stopper by pushing straight down (Figure D). The vacuum will draw the diluent into the ADVATE vial.
  8. Swirl gently until ADVATE is completely dissolved.

Do not refrigerate after reconstitution.

Administration

ADVATE is intended for intravenous use after reconstitution only.

  • Inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit. The solution should be clear and colorless in appearance. If not, do not use the solution and notify Baxter immediately.
  • Administer ADVATE at room temperature not more than 3 hours after reconstitution.
  • Plastic syringes must be used with this product, since proteins such as ADVATE tend to stick to the surface of glass syringes.
  1. Use aseptic technique.
  2. Remove the blue cap from the BAXJECT II device. Connect the syringe to the BAXJECT II device (Figure E). DO NOT INJECT AIR.
  3. Turn the system upside down (factor concentrate vial now on top). Draw the factor concentrate into the syringe by pulling the plunger back slowly (Figure F).
  4. Disconnect the syringe; attach a suitable needle and inject intravenously as instructed under Administration by Bolus Infusion.
  5. If a patient is to receive more than one vial of ADVATE, 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 ADVATE and Sterile Water for Injection only, therefore reconstituting and withdrawing a second vial into the syringe requires a second BAXJECT II device.

Administration by bolus infusion

Administer a dose of ADVATE over a period of ≤ 5 minutes (maximum infusion rate, 10 mL/min). Determine the pulse rate before and during administration of ADVATE. 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.

Figure A Figure B Figure C

4. 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

6. 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.


Figure D Figure E Figure F

Turn the system over, so that the diluent vial is on top. Quickly insert the white plastic spike fully into the ADVATE vial stopper by pushing straight down. The vacuum will draw the diluent into the ADVATE vial.

2. Remove the blue cap from the BAXJECT II device. Connect the syringe to the BAXJECT II device. DO NOT INJECT AIR.

Turn the system upside down (factor concentrate vial now on top). Draw the factor concentrate into the syringe by pulling the plunger back slowly

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