"The U.S. Food and Drug Administration is alerting hospitals, health care professionals, and patients of a voluntary recall of all non-expired drug products produced and distributed for sterile use by Abrams Royal Compounding Pharmacy in Dallas, T"...
The use of RECOMBINATE (antihemophilic factor (recombinant)) rAHF is indicated in hemophilia A (classical hemophilia) for the prevention and control of hemorrhagic episodes.1 RECOMBINATE (antihemophilic factor (recombinant)) rAHF is also indicated in the perioperative management of patients with hemophilia A (classical hemophilia).
RECOMBINATE (antihemophilic factor (recombinant)) rAHF can be of therapeutic value in patients with acquired AHF inhibitors not exceeding 10 Bethesda Units per mL2. In clinical studies with RECOMBINATE (antihemophilic factor (recombinant)) 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 (antihemophilic factor (recombinant)) rAHF should be controlled by frequent laboratory determinations of circulating AHF levels.
DOSAGE AND ADMINISTRATION
Each bottle of RECOMBINATE (antihemophilic factor (recombinant)) 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 x 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 x 40 = 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 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.|
|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
- Bring RECOMBINATE, Antihemophilic Factor (Recombinant) (rAHF) (dry concentrate) and Sterile Water for Injection, USP, (diluent) to room temperature.
- Remove caps from concentrate and diluent bottles.
- Cleanse stoppers with germicidal solution and allow to dry prior to use.
- Remove protective covering from one end of double-ended needle and insert exposed needle through the center of the stopper.
- Remove protective covering from other end of double-ended needle. Invert diluent bottle over the upright RECOMBINATE (antihemophilic factor (recombinant)) rAHF bottle, then rapidly insert free end of the needle through the RECOMBINATE (antihemophilic factor (recombinant)) rAHF bottle stopper at its center. The vacuum in the bottle will draw in the diluent.
- Disconnect the two bottles by removing needle from diluent bottle stopper, then remove needle from RECOMBINATE (antihemophilic factor (recombinant)) rAHF bottle. Swirl gently until all material is dissolved. Be sure that RECOMBINATE (antihemophilic factor (recombinant)) 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 (antihemophilic factor (recombinant)) 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 solut ion and container permit. A colorless to faint yellow appearance is acceptable for RECOMBINATE (antihemophilic factor (recombinant)) 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.
- Attach filter needle to a disposable syringe and draw back plunger to admit air into the syringe.
- Insert needle into reconstituted RECOMBINATE (antihemophilic factor (recombinant)) rAHF.
- Inject air into bottle and then withdraw the reconstituted material into the syringe.
- Remove and discard the filter needle from the syringe; attach a suitable needle and inject intravenously as instructed under Rate of Administration.
- If a patient is to receive more than one bottle of RECOMBINATE (antihemophilic factor (recombinant)) 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 (antihemophilic factor (recombinant)) 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 (antihemophilic factor (recombinant)) 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.
RECOMBINATE (antihemophilic factor (recombinant)) rAHF is available in single-dose bottles which contain nominally 250, 500 and 1000 International Units per bottle. RECOMBINATE (antihemophilic factor (recombinant)) 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.
RECOMBINATE (antihemophilic factor (recombinant)) 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 box.
1. White GC, McMillan CW, Kingdon HS, et al: Use of recombinant antihemophilic factor in the treatment of two patients with classic hemophilia. New Eng J Med 320:166-170, 1989
2. Kessler CM: An Introduction to Factor VIII Inhibitors: The Detection and Quantitation. Am J Med 91 (Suppl 5A):1S-5S, 1991
8. Abildgaard CF, Simone JV, Corrigan JJ, et al: Treatment of hemophilia with glycine-precipitated Factor VIII. New Eng J Med 275:471-475, 1966
9. Schimpf K, Rothman P, Zimmermann K: Factor VIII dosis in prophylaxis of hemophilia A; A further controlled study in Proc XIth Cong W.F.H. Kyoto, Japan, Academic Press, 1976, pp 363-366
To enroll in the confidential, industry-wide Patient Notification System, call 1-888-UPDATE U (1-888-873-2838). Manufactured by: Baxter Healthcare Corporation Westlake Village, CA 91362, USA. Revised December 2004.
Last reviewed on RxList: 2/20/2009
This monograph has been modified to include the generic and brand name in many instances.
Additional Recombinate Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.