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Recombinate (Antihemophilic Factor) - Indications and Dosage

 
 



INDICATIONS AND USAGE

The use of RECOMBINATE rAHF is indicated in hemophilia A (classical hemophilia) for the prevention and control of hemorrhagic episodes.1 RECOMBINATE rAHF is also indicated in the perioperative management of patients with hemophilia A (classical hemophilia).

RECOMBINATE rAHF can be of therapeutic value in patients with acquired AHF inhibitors not exceeding 10 Bethesda Units per mL2. In clinical studies with RECOMBINATE rAHF, patients with inhibitors who were entered into the previously treated patient trial and those previously untreated children who have developed inhibitor activity on study, showed clinical hemostatic response when the titer of inhibitor was less than 10 Bethesda Units per mL. However, in such uses, the dosage of RECOMBINATE rAHF should be controlled by frequent laboratory determinations of circulating AHF levels.

RECOMBINATE rAHF is not indicated in von Willebrand's disease.

DOSAGE AND ADMINISTRATION

Each bottle of RECOMBINATE rAHF is labeled with the AHF activity expressed in IU per bottle. 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 AHF 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 8 and is supported by the data generated by 419 clinical pharmacokinetic studies with rAHF 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.

Example (Assuming patient's baseline AHF level is at <1%):

  1. A dose of 1750 IU AHF administered to a 70 kg patient, i.e. 25 IU/kg (1750/70), should be expected to cause a peak post-infusion AHF increase of 25 × 2 = 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 70/2 × 40 = 1400 IU.

RECOMMENDED DOSAGE SCHEDULE

Physician supervision of the dosage is required. The following dosage schedule may be used as a guide.

Hemorrhage   
Degree of hemorrhage Required peak post-infuson
AHF activity in the blood (as % of normal or IU/dL plasma)
Frequency of infusion
Early hemarthrosis or muscle bleed or oral bleed 20-40 Begin infusion every 12 to 24 hours for one-three days until the bleeding episode as indicated by pain is resolved or healing is achieved.
More extensive hemarthrosis, muscle bleed, or hematoma 30-60 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 60-100 Repeat infusion every 8 to 24 hours until threat is resolved.
Surgery
Type of Operation
Minor surgery, including tooth extraction 60-80 A single infusion plus oral antifibrinolytic therapy within one hour is sufficient in approximately 70% of cases.
Major surgery 80-100 (pre- and post-operative) Repeat infusion every 8 to 24 hours depending on state of healing.

The careful control of the substitution therapy is especially important in cases of major surgery or life threatening hemorrhages.

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

Other dosage regimens have been proposed such as that of Schimpf, et al, which describes continuous maintenance therapy.9

RECONSTITUTION: USE ASEPTIC TECHNIQUE

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

NOTE: Do not refrigerate after reconstitution. See Administration.

ADMINISTRATION: USE ASEPTIC TECHNIQUE

Administer at room temperature.

RECOMBINATE rAHF 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. A colorless to faint yellow appearance is acceptable for RECOMBINATE rAHF.

Plastic syringes are recommended for use with this product since proteins such as AHF tend to stick to the surface of all-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 RECOMBINATE rAHF.
  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 Rate of Administration.
  5. If a patient is to receive more than one bottle of RECOMBINATE rAHF, the contents of 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 RECOMBINATE rAHF only.

RATE OF ADMINISTRATION

Preparations of RECOMBINATE, Antihemophilic Factor (Recombinant) (rAHF) can be administered at a rate of up to 10 mL per minute with no significant reactions.

The pulse rate should be determined before and during administration of RECOMBINATE rAHF. 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

RECOMBINATE rAHF is available in single-dose bottles which contain nominally 250, 500 and 1000 International Units per bottle. RECOMBINATE rAHF is packaged with 10 mL of Sterile Water for Injection, USP, a double-ended needle, a filter needle, one physician insert and one patient insert.

STORAGE

RECOMBINATE rAHF can be stored under refrigeration [2°-8°C (36°-46°F)] or at room temperature, not to exceed 30°C (86°F). Avoid freezing to prevent damage to the diluent bottle. Do not use beyond the expiration date printed on the bottle.

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