"The U.S. Food and Drug Administration today notified Ranbaxy Laboratories, Ltd., that it is prohibited from manufacturing and distributing active pharmaceutical ingredients (APIs) from its facility in Toansa, India, for FDA-regulated drug product"...
The use of Antihemophilic Factor (Recombinant), Bioclate (antihemophilic factor) TM is indicated in hemophilia A (classical hemophilia) for the prevention and control of hemorrhagic episodes.1 Bioclate (antihemophilic factor) TM is also indicated in the perioperative management of patients with hemophilia A (classical hemophilia).
Bioclate (antihemophilic factor) TM can be of significant therapeutic value in patients with acquired AHF inhibitors not exceeding 10 Bethesda Units per mL.2 In clinical studies with Bioclate (antihemophilic factor) TM, 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 s.c. uses, the dosage of Bioclate (antihemophilic factor) TM should be controlled by frequent laboratory determinations of circulating AHF levels.
Bioclate (antihemophilic factor) TM is not indicated in von Willebrands disease.
DOSAGE AND ADMINISTRATION
Each bottle of Bioclate (antihemophilic factor) TM 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. The high purity of Bioclate (antihemophilic factor) TM has been thought to influence the difficulty of producing an accurate potency measurement in vitro.
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 Factor.
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 b.d. weight (IU/kg) by two. This calculation is based on the clinical findings of Abildgaard et al8 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 preinfusion baseline of approximately 2.0 IU/dL per IU/kg b.d. weight.
Example (Assuming patients baseline AHF level is at < 1%):
- A dose of 1750 IU AHF administered to a 70 kg patient, i.e. 25 IU/kg (1 750/70), should be expected to cause a peak postinfusion AHF increase of 25 x 2 = 50 IU/dL (50% of normal).
- 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. 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 patients plasma at suitable intervals to assure that adequate AHF levels have been reached and are maintained. Other dosage regimens have been proposed s.c. as that of Schimpf, et al, which describes continuous maintenance therapy.9
Use Aseptic Technique
- Bring Antihemophilic Factor (Recombinant), Bioclate (antihemophilic factor) TM, (dry concentrate) and Sterile Water for Injection, USP, (diluent) to room temperature.
- Remove caps from concentrate and diluent bottles to expose central portion of rubber stoppers.
- 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 diluent stopper.
- Remove protective covering from other end of double-ended needle. Invert diluent bottle over the upright Bioclate (antihemophilic factor) TM bottle, then rapidly insert free end of the needle through the Bioclate (antihemophilic factor) TM 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 Bioclate (antihemophilic factor) TM bottle. Swirl gently until all material is dissolved. Be sure that Bioclate (antihemophilic factor) TM is completely dissolved, otherwise active material will be removed by the filter.
NOTE: Do not refrigerate after reconstitution. See Administration.
Use Aseptic Technique
Administer at room temperature. Bioclate (antihemophilic factor) TM should be administered not more than 3 hours after reconstitution.
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 Antihemophilic Factor (Recombinant), Bioclate (antihemophilic factor) TM.
Plastic syringes are recommended for use with this product since proteins such as AHF tend to stick to the ground-glass surface of all-glass syringes.
- Attach filter needle to a disposable syringe and draw back plunger to admit air into syringe.
- Insert needle into reconstituted Bioclate (antihemophilic factor) TM.
- 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 Bioclate (antihemophilic factor) TM, the contents of multiple 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 Bioclate (antihemophilic factor) TM. Please note, filter needles are intended to filter the contents of a single bottle of Bioclate (antihemophilic factor) TM only.
Rate of Administration
Preparations of Bioclate (antihemophilic factor) TM 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 Bioclate (antihemophilic factor) TM. 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.
Antihemophilic Factor (Recombinant), Bioclate (antihemophilic factor) TM is available in single-dose bottles which contain nominally 250, 500 and 1000 International Units per bottle. Bioclate (antihemophilic factor) TM is packaged with 10 mL of Sterile Water for Injection, USP, a double-ended needle, and a filter needle.
Bioclate (antihemophilic factor) TM 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.
- 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 320:1 66-1 70, 1989
- Kessler CM: An Introduction to Factor VIII Inhibitors: The Detection and Quantitation. Am J Med 91 (Suppl 5A): 1 S-5S, 1991
- Schwarzinger I, Pabinger I, Korninger C, Haschke F, Kundi M, Niessner H, Lechner K: Incidence of inhibitors in patients with severe and moderate hemophilia A treated with factor VIII concentrates. Am J Hematology 24:241 -245, 1987
- Penner JA, Kelly PE: Management of patients with factor VIII or IX inhibitors. Sem Thromb Hemostasis 1:386-399, 1975
- Ehrenforth S, Kreuz W, Scharrer I, et al: Incidence of development of factor VIII and factor IX inhibitors in haemophiliacs. Lancet 339:594-598, 1992
- McMillan CW, Shapiro SS, Whitehurst D, et al: The natural history of factor VIII inhibitors in patients with hemophilia A: a national cooperative study. II. Observations on the initial development of factor Vlll:C inhibitors. Blood 71:344-348, 1988
- Addiego JE Jr., Gomperts E, Liu S, et al: Treatment of hemophilia A with a highly purified Factor VIII concentrate prepared by Anti-FVIIIc immunoaffinity chromatography. Thrombosis and Haemostasis 67:19-27, 1992
- Abildgaard CE, Simone JV, Corrigan JJ, et al: Treatment of hemophilia with glycine-precipitated Factor VIII. New Eng J Med 275:471 -475, 1966
- Schimpf K, Rothmann 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
- Gill EM: The Natural History of Factor VIII Inhibitors in Patients With Hemophilia A. Hoyer LW (ed), Factor VIII lnhtbitors, N.Y., AR Liss, 1984, pp 19-29
- RasiV, Ikkala E: Haemophiliacs with factor VIII inhibitors in Finland: prevalence, incidence and outcome. Br J Haematol 76:369-371, 1990
- Lusher JM, Salzman PM: Viral Safety and Inhibitor Development Associated With Factor VIIIC Ultra-Purified From Plasma in Hemophiliacs Previously Unexposed to Factor VIIIC Concentrates. Seminars in Hematology 27:1-7, 1990
Last reviewed on RxList: 12/8/2004
This monograph has been modified to include the generic and brand name in many instances.
Additional Bioclate 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.