Hemofil M (Antihemophilic Factor) - Indications and Dosage

INDICATIONS AND USAGE

The use of HEMOFIL M, Antihemophilic Factor (Human) (AHF), Method M, Monoclonal Purified, is indicated in hemophilia A (classical hemophilia) for the prevention and control of hemorrhagic episodes.

HEMOFIL M AHF can be of significant therapeutic value in patients with acquired Factor VIII inhibitors not exceeding 10 Bethesda Units per mL.³ However, in such uses, the dosage should be controlled by frequent laboratory determinations of circulating AHF.

HEMOFIL M AHF is not indicated in von Willebrand's disease.

DOSAGE AND ADMINISTRATION

Each bottle of HEMOFIL M AHF is labeled with the AHF activity expressed in IU per bottle. This potency assignment is referenced to the World Health Organization International Standard.

The high purity of HEMOFIL M AHF has been thought to influence the difficulty of producing an accurate potency measurement. Experiments have shown that to achieve accurate activity levels, such a potency assay should be conducted using plastic test tubes and pipets as well as substrate containing normal levels of von Willebrand's Factor.

The expected in vivo peak AHF level, expressed as IU/dL of plasma or % (percent) of normal, can be calculated by multiplying the dose administered per kg body weight (IU/kg) by two. This calculation is based on the clinical finding by Abildgaard, et al,⁴ which is supported by data from the collaborative study of in vivo recovery and survival with 15 different lots of HEMOFIL M AHF on 56 hemophiliacs that demonstrated a mean peak recovery point above the mean pre-infusion baseline of about 2.0 IU/dL per infused IU/kg body weight.⁵

Example:

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.

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 bee reached and are maintained.

Other dosage regimens have been proposed such as that of Schimpf, et al, which describes continuous maintenance therapy.⁶

RECONSTITUTION: USE ASEPTIC TECHNIQUE

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

Note: Do not refrigerate after reconstitution.

ADMINISTRATION: USE ASEPTIC TECHNIQUE

Administer at room temperature.

HEMOFIL M, Antihemophilic Factor (Human) (AHF), Method M, Monoclonal Purified, should be administered not more than three 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.

Plastic syringes are recommended for use with this product. The ground glass surface of all-glass syringes tend to stick with solutions of this type.

1. Attach filter needle to a disposable syringe and draw back plunger to admit air into syringe.
2. Insert needle into reconstituted HEMOFIL M AHF.
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 HEMOFIL M AHF, the contents of two bottles may be drawn into the same syringe by drawing up each bottle through a separate unused filter needle. This practice lessens the loss of HEMOFIL M AHF. Please note, filter needles are intended to filter the contents of a single bottle of HEMOFIL M AHF only.

RATE OF ADMINISTRATION

Preparations of HEMOFIL M AHF 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 HEMOFIL M AHF. Should a significant increase occur, reducing the rate of administration or temporarily halting the injection usually allows the symptoms to disappear promptly.

HOW SUPPLIED

HEMOFIL M AHF is available as single dose bottles. Each bottle is labeled with the potency in International Units, and is packaged together with 10 mL of Sterile Water for Injection, USP, a double-ended needle, and a filter needle.

STORAGE

HEMOFIL M AHF can be stored under refrigeration [2°-8°C (36°-46°F)] or at room temperature, not to exceed 30°C (86°F), until expiration date noted on the package. Avoid freezing to prevent damage to the diluent bottle.