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Advate (Antihemophilic Factor) - Indications and Dosage

 
 



INDICATIONS AND USAGE

ADVATE rAHF-PFM is indicated in hemophilia A (classical hemophilia) for the prevention and control of bleeding episodes. ADVATE rAHF-PFM is also indicated in the perioperative management of patients with hemophilia A. ADVATE rAHF-PFM can be of therapeutic value in patients with Factor VIII inhibitors not exceeding 10 Bethesda Units (BU) per mL.1, 2 However, in patients with a known or suspected inhibitor to Factor VIII, the plasma Factor VIII level should be monitored frequently and the dose of ADVATE rAHF-PFM should be adjusted accordingly.

ADVATE rAHF-PFM is not indicated for the treatment of von Willebrand's disease.

DOSAGE AND ADMINISTRATION

Each vial of ADVATE rAHF-PFM is labeled with the rAHF activity expressed in IU per vial. This potency assignment employs a Factor VIII concentrate standard that is referenced to a WHO International Standard for Factor VIII:C Concentrates, 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 2. This calculation is based on the findings of several pharmacokinetic studies of rAHF concentrates, 10, 11, 12, 13 and is supported by the data generated by 223 pharmacokinetic studies with ADVATE rAHF-PFM in 107 Phase 2/3 pivotal study subjects. These pharmacokinetic data demonstrated a peak post-infusion recovery of approximately 1.5-2.5 IU/dL per IU/kg above the pre-infusion baseline.

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

  1. A dose of 1,750 IU ADVATE rAHF-PFM administered to a 70 kg patient should be expected to result in a peak post-infusion Factor VIII increase of 1750 IU × {[2IU/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 70 IU/dL/{[2IU/dL]/[IU/kg]} × 40 kg = 1400 IU.

RECOMMENDED DOSE SCHEDULE

Physician supervision of the treatment regimen is required. A guide for dosing in the treatment of hemorrhages is provided in Table 8. A guide for dosing in perioperative management is provided in Table 9. The careful control of replacement therapy is especially important in cases of major surgery or life-threatening hemorrhages.

Table 8.
Guide to ADVATE rAHF-PFM Dosing for Treatment of Hemorrhages
Degree of Hemorrhage Required Peak Post infusion Factor VIII Activity in the Blood (as % of normal or IU/dL) Frequency of Infusion
Early hemarthrosis, muscle bleeding episode, or mild oral bleeding episode 20-40 Begin infusions every 12 to 24 hours for one to three days until the bleeding episode is resolved (as indicated by relief of pain) or healing is achieved.
More extensive hemarthrosis, muscle bleeding episode, or hematoma 30-60 Repeat infusions every 12 to 24 hours for (usually) three days or more until pain and disability are resolved.
Life-threatening bleeding episodes such as head injury, throat bleeding episode, or severe abdominal pain 60-100 Repeat infusions every 8 to 24 hours until resolution of the bleeding episode has occurred.

Table 9.
Guide to ADVATE rAHF-PFM Dosing for Surgical Procedures
Type of Procedure Required Peak Post infusion Factor VIII Activity in the Blood (as % of Normal or IU/dL) Frequency of Infusion
Minor surgery, including tooth extraction 60-100 Give a single bolus infusion beginning within one hour of the operation, with optional additional dosing every 12-24 hours as needed to control bleeding. For dental procedures, adjunctive therapy may be considered.
Major surgery 80-120
(pre- and post-operative)
For bolus infusion replacement, repeat infusions every 8 to 24 hours, depending on the desired level of Factor VIII and state of wound healing.

Although dose can be estimated by the calculations above, it is highly recommended that, whenever possible, appropriate laboratory tests including serial Factor VIII activity assays be performed on the patient's plasma at suitable intervals to assure that adequate Factor VIII levels have been reached and are maintained.

RECONSTITUTION: USE ASEPTIC TECHNIQUE

  1. Bring the ADVATE rAHF-PFM (dry concentrate) and Sterile Water for Injection (diluent) to room temperature.
  2. Remove caps from the concentrate and diluent vials.
  3. Cleanse stoppers with germicidal solution, and allow to dry prior to use.
  4. Remove protective covering from one end of the double-ended needle and insert exposed needle through the center of the stopper.
  5. Remove protective covering from the other end of the double-ended needle. Invert diluent bottle over the upright ADVATE rAHF-PFM bottle, then rapidly insert the free end of the needle through the ADVATE rAHF-PFM bottle stopper at its center. The vacuum in the bottle will draw in the diluent.
  6. Disconnect the two bottles by removing the needle from the diluent bottle stopper, then remove the needle from the ADVATE rAHF-PFM bottle. Swirl gently until all material is dissolved. Be sure that ADVATE rAHF-PFM is completely dissolved, otherwise active materials will be removed by the filter needle.

NOTE:    Do not refrigerate after reconstitution.

ADMINISTRATION: USE ASEPTIC TECHNIQUE

Parenteral drug products should be inspected for particulate matter and discoloration prior to administration, whenever solution and container permit. A colorless appearance is acceptable for ADVATE rAHF-PFM. ADVATE rAHF-PFM should be administered at room temperature not more than 3 hours after reconstitution. Plastic syringes must be used with this product, since proteins such as ADVATE rAHF-PFM tend to stick to the surface of glass syringes.

  1. Attach filter needle to a disposable syringe and draw back plunger to admit air into the syringe.
  2. Insert needle into reconstituted ADVATE rAHF-PFM.
  3. Inject air into bottle and then withdraw the reconstituted material into the syringe.
  4. Remove and discard the filter needle from 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 bottle of ADVATE rAHF-PFM, the contents of the multiple bottles may be drawn into the same syringe by drawing up each bottle through a separate unused filter needle. Filter needles are intended to filter the contents of a single bottle of ADVATE rAHF-PFM only.

ADMINISTRATION BY BOLUS INFUSION

A dose of ADVATE rAHF-PFM should be administered over a period of </= 5 minutes (maximum infusion rate, 10 mL/min). The pulse rate should be determined before and during administration of ADVATE rAHF-PFM. 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.

HOW SUPPLIED

ADVATE rAHF-PFM is available in single-dose vials that contain nominally 250, 500, 1000, and 1500 IU per vial. ADVATE rAHF-PFM is packaged with 5 mL of Sterile Water for Injection, a double-ended needle, a filter needle, infusion set/blood collection set *, 10 mL sterile syringe, alcohol swabs, bandages, one full prescribing physician insert, and one patient insert.

STORAGE

ADVATE rAHF-PFM should be refrigerated (2°-8°C [36°-46°F]). Avoid freezing to prevent damage to the diluent vial. ADVATE rAHF-PFM may be stored at room temperature (22°-28°C [72°-82°F]) for a period of up to 6 months until the expiration date. Do not use beyond the expiration date printed on the vial.


* Approved for both indications under 510(k).

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