"The U.S. Food and Drug Administration today approved Tretten, Coagulation Factor XIII A-Subunit (Recombinant), the first recombinant product for use in the routine prevention of bleeding in adults and children who have a rare clotting disorder, k"...
Autoplex® T, Anti-Inhibitor Coagulant Complex, Heat Treated, is indicated for use in patients with Factor VIII inhibitors who are bleeding or are to undergo surgery.2-5 The intravenous administration of this preparation is intended to control bleeding episodes in such patients.
Approximately 10% of individuals with hemophilia A (classical hemophilia) have laboratory-measurable inhibitors to Factor VIII.6 For these patients, the treatment of choice depends upon the following factors: the severity of the bleeding episode, the existing level of inhibitor and whether the patient responds to infusion of Factor VIII with increasing antibody titers (anamnestic rise of Factor VIII antibody).
The following table is presented as a guide in determining the preferred therapy with respect to the use of Anti-Inhibitor Coagulant Complex or Antihemophilic Factor (Human) in patients with Factor VIII inhibitors. Inhibitor level categories are given in the shaded areas of the table and the corresponding recommended product or products are given in the unshaded areas. Other regimens have been proposed.7
|PRESENT LEVEL OF FACTOR VIII INHIBITOR||HISTORICAL MAXIMUM LEVEL OF FACTOR VIII INHIBITOR||< 2 B.U.a||2-10 B.U.||> 10 B.U.|
|< 2 B.U.||AHFb||AICCc or AHF||AICC|
|2-10 B.U.||AICCor AHF||AICCor AHF||AICC|
|> 10 B.U.||AICC||AICC||AICC|
| a B.U. designates Bethesda Units.
b AHF designates Antihemophilic Factor (Human).
c AICC designates Anti-Inhibitor Coagulant Complex.
Patients whose present Factor VIII inhibitor levels are greater than 10 Bethesda Units, as well as patients whose inhibitor levels are historically known to rise to greater than 10 Bethesda Units following treatment with Antihemophilic Factor (Human), should be treated with Anti-Inhibitor Coagulant Complex.
Patients whose present Factor VIII inhibitor levels are between 2 and 10 Bethesda Units and whose inhibitor levels are historically known to remain in this range following treatment with Antihemophilic Factor (Human) may be treated with either Antihemophilic Factor (Human) or Anti-Inhibitor Coagulant Complex, depending on the patient's clinical history and the severity of the bleeding episode.
Patients with Factor VIII inhibitor levels of less than 2 Bethesda Units whose inhibitor levels are historically known to remain at 2 Bethesda Units or less following treatment with Antihemophilic Factor (Human) may be treated with appropriate doses of Antihemophilic Factor (Human).
For patients who have low levels of Factor VIII inhibitor and whose history does not include adequate laboratory indications of an anamnestic response to Antihemophilic Factor (Human), the treatment of choice should be based on clinical judgement. In such patients who are having non-critical or minor bleeding episodes, the use of Autoplex® T, Anti-Inhibitor Coagulant Complex, Heat Treated, will maintain the inhibitor at a low level and allow the use of other coagulant therapeutic agents in subsequent major emergencies.
DOSAGE AND ADMINISTRATION
Each bottle of Autoplex® T, Anti-Inhibitor Coagulant Complex, Heat Treated, is labeled with the number of Hyland Factor VIII Correctional Units that it contains. One Hyland Factor VIII Correctional Unit is that quantity of activated prothrombin complex which, upon addition to an equal volume of Factor VIII deficient or inhibitor plasma, will correct the clotting time (ellagic acid-activated partial thromboplastin time) to 35 seconds (normal).
The recommended dosage range is 25 to 100 Hyland Factor VIII Correctional Units per kg of body weight, depending upon the severity of hemorrhage. If no hemostatic improvement is observed approximately 6 hours following the initial administration, the dosage should be repeated.
Subsequent dosage and administration intervals should be adjusted according to the patient's clinical response. (See Laboratory Tests.)
Reconstitution: Use Aseptic Technique
- Bring Autoplex® T, Anti-Inhibitor Coagulant Complex, Heat Treated, (dry concentrate), and Sterile Water for Injection, USP, (30 mL) (diluent) to room temperature.
- Remove caps from concentrate and diluent bottles to expose central portions of rubber stoppers.
- Cleanse stoppers with germicidal solution.
- Remove protective covering from one end of the double-ended needle and insert exposed needle through diluent stopper.
- Remove protective covering from the other end of the double-ended needle. Invert diluent bottle over the upright concentrate bottle, then rapidly insert free end of the needle through the concentrate bottle stopper at its center. Vacuum in the concentrate bottle will draw in diluent.
- Disconnect the two bottles by removing needle from the diluent bottle, then remove needle from concentrate bottle stopper. Swirl or rotate the concentrate bottle until all material is dissolved. Do not shake vigorously.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Note: Do not refrigerate after reconstitution.
Rate of Administration
It is recommended that Autoplex® T, Anti-Inhibitor Coagulant Complex, Heat Treated, be infused initially at a rate of 2 mL/min. If infusion at this rate is well tolerated the administration rate may be gradually increased to 10 mL/min.
Administration: Use Aseptic Technique
When reconstitution of Autoplex® T, Anti-Inhibitor Coagulant Complex, Heat Treated, is complete, its infusion should commence as soon as practical; however, it must be completed within 1 hour.
The reconstituted solution should be at room temperature during infusion.
Intravenous Drip Infusion
When a Hyland administration set is used, follow directions for use printed on the administration set container. When an administration set from another source is used, follow directions accompanying that set where necessary. The use of a Hyland administration set is recommended as it contains a suitable filter.
Intravenous Syringe Injection
- Attach filter needle to syringe and draw back plunger to admit air into the syringe.
- Insert needle into the reconstituted Autoplex® T (anti-inhibitor coagulant complex, heat treated) , Anti-Inhibitor Coagulant Complex, Heat Treated.
- 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 patient is to receive more than one bottle of concentrate, 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 concentrate. Please note: filter needles are intended to filter the contents of a single bottle of Autoplex® T (anti-inhibitor coagulant complex, heat treated) , Anti-Inhibitor Coagulant Complex, Heat Treated, only.
Autoplex® T, Anti-Inhibitor Coagulant Complex, Heat Treated, is packaged with 30 mL Sterile Water for Injection, USP; a double-ended needle; a filter needle; and a package insert.
Autoplex® T, Anti-Inhibitor Coagulant Complex, Heat Treated, should be stored under ordinary refrigeration (2 - 8°C, 36 - 46°F). Avoid freezing to prevent damage to the diluent bottle.
2. Kurczynski EM, Penner JA: Activated prothrombin concentrate for patients with factor VIII inhibitors. New Eng J Med 291:164-167, 1974
3. Penner JA, Kelly PE: Management of patients with factor VIII or IX inhibitors. Semin Thromb Hemostas 1:386-399, 1975
4. Buchanan GR, Kevy SV: Use of prothrombin complex concentrates in hemophiliacs with inhibitors: Clinical and laboratory studies. Pediatrics 62:767-774, 1978
5. Mannucci PM, Federici F, Vigano S, et al: Multiple dental extractions with a new prothrombin complex concentrate in two patients with factor VIII inhibitors. Thromb Res 15:359-364, 1979
6. Shapiro SS: Antibodies to blood coagulation factors. Clinics in Haematology 8:207-214, 1979
7. Roberts HR: Hemophiliacs with inhibitors: Therapeutic options. New Eng J. Med 305:757-758, 1981
Abildgaard CF, Penner JA, Watson-Williams EJ: Anti-Inhibitor Coagulant Complex (Autoplex) for treatment of factor VIII inhibitors in hemophilia. Blood 56:978, 1980
Fekete L F, Holst SL, Peetoom F, et al: “Auto” Factor IX Concentrate: A new therapeutic approach to treatment of hemophilia A patients with inhibitors. Proceedings, 14th International Congress of Haematology. Sao Paulo, Brazil, 1972
Horwith G, Revie DR. Efficacy of viral clearance methods used in the manufacture of activated concentrates: focus on AUTOPLEX® T. Haemophilia 5 (Supple 3): 19, 1999
Kantrowitz JL et al. Early experience with the use of Anti-Inhibitor Coagulant Complex to treat bleeding in hemophiliacs with inhibitors to factor VIII. Clin Ther 9 (4): 405, 1987
Kelly P, Penner JA: Antihemophilic factor inhibitors: Management with prothrombin complex concentrates. JAMA 236:2061, 1976
Lundblad RL et al. Measurement of active coagulation factors in Autoplex® T with colorimetric active site-specific assay technology. Thrombosis and Haemostatsis 80 (5): 3, 1998
Seligsohn U, Kasper CK, ěsterud B, et al: Activated factor VII. Presence in factor IX concentrates and persistence in the circulation after infusion. Blood 53:828, 1979
White, GC, Seventeen years' experience with Autoplex®/Autoplex® T (anti-inhibitor coagulant complex, heat treated) : evaluation of inpatients with severe haemophilia A and factor VIII inhibitors at major haemophilia centre. HAEMOPHILIA: Vol. 6, No. 5, 508-512, 2000.
Distributed by: Nabi®, Boca Raton, FL 33487 USA. Manufactured by: Baxter Healthcare Corporation, Glendale, CA 91203 USA. FDA rev date: n/aThis monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 1/13/2009
Additional Autoplex-T 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.