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Factor IX Complex, Konyne (factor ix complex) ® 80 is indicated for the prevention and control of bleeding caused by Factor IX deficiency due to hemophilia B.
Konyne (factor ix complex) 80 is not indicated for use in the treatment of factor VII deficiency.
Konyne (factor ix complex) 80 is appropriate for use in:
- Hemophilia B (Christmas disease); demonstrated factor IX deficiency in children or adults with real or impending bleeding episodes. Spontaneous bleeding can occur even in the absence of any trauma.
- Reversal of coumarin anticoagulant induced hemorrhage; in situations where prompt reversal is required (e.g., preceding emergency surgery, trauma, etc.), administration of fresh-frozen plasma should be initially considered as treatment; however, Konyne (factor ix complex) 80 may be considered as a secondary approach if the risk of transmitting hepatitis is considered justifiable in the face of a life-threatening situation. 6 - 8
- Treatment of bleeding episodes in patients with hemophilia A (factor VIII deficiency) who have inhibitors to factor VIII. 9
In addition to coumarin anticoagulant induced deficiencies, low levels of factors II, VII, IX and X may be found in vitamin K deficiency, in patients with gut sterilization due to oral antibiotics, in patients with liver disease, and in those with nephrotic syndrome. However, Factor IX Complex, Konyne (factor ix complex) 80® is not indicated in these situations and treatment should be aimed at correcting the primary condition.
Note: For publications on the clinical use of Konyne (factor ix complex) ®, please refer to references 1,2, 6-17.
DOSAGE AND ADMINISTRATION
Each bottle of Konyne 80 has the factor IX activity, in IU, stated on the bottle label. One IU is defined as the activity present in 1 mL of fresh, normal plasma. The potency is standardized in terms of factor IX content.
The amount of Konyne (factor ix complex) 80 required for normalizing hemostasis will depend upon the patient and upon the circumstances. Sufficient Konyne (factor ix complex) 80 should be administered to achieve and maintain a plasma level of at least 20% until hemostasis is achieved.
Levels of factor IX of 30 to 40 percent are considered effective in stopping hemorrhages. 1 Bleeds in life- or limb-threatening areas require factor IX levels of 50 to 80 percent which should be maintained at 30 to 40 percent for a few days. 1 The desired hemostatic plasma level in surgical patients for minor procedures or invasive dental surgery is between 30 and 40 percent of normal. 1 This can be achieved by a dosage not exceeding 30 to 40 units per kg body weight. In major hemorrhage, as during surgery or severe accidental trauma, plasma levels of 60 to 80 percent just prior to surgery, maintained above 30 percent for a further 5 to 7 days and then above 15 to 20 percent for 7 to 10 additional days, until healing occurs, are required. 1
While the range of values in normal clinical practice is likely to vary depending upon differences between patients, their clinical condition and the type of assay employed, it is again stressed that high dosages, especially if frequently repeated (e.g., more than once per day) are hazardous. Such regimens can induce major thrombotic complications and hence must be avoided.
The following formulas may be used as guidelines to calculate an appropriate dose or to estimate the expected percentage increase obtained from a given dose:
|Expected factor IX = IU administered x 1.0 |
increase (in % of normal) body weight (in kg)
|IU required = body weight (kg) x desired factor IX increase (% normal) x 1.0|
Thus, in order to bring a 70 kg patient from 0% to 50% of normal, the patient would require 70 x 50 x 1.0 = 3500 IU or 50 IU/kg body weight.
The ideal treatment for proven congenital deficiency of procoagulants is prophylactic administration. For prophylaxis against hemorrhage during times of extensive physical activity, the plasma factor IX levels should be raised to 15 to 30 percent. Maintenance dosage should be adapted to the individual patient's needs. Additional Factor IX Complex, Konyne (factor ix complex) ® 80 should be administered when a patient on prophylaxis is exposed to trauma or surgery.
Maintenance dosage should be administered according to the clinical response and the factor IX level achieved. Such dosage is usually about 10-20 IU per kg body weight per day.
For treatment of bleeding episodes in patients with hemophilia A (factor VIII deficiency) who have inhibitors to factor VIII, the recommended dose should be 75 IU/kg. A second dose may be administered after 12 hours if necessary. 9
- Warm the unopened diluent and concentrate to room temperature (NMT 37°C, 99°F).
- After removing the plastic flip-top caps aseptically cleanse the rubber stoppers of both bottles.
- Remove the protective cover from the plastic transfer-needle cartridge with tamper-proof seal and penetrate the stopper of the diluent bottle.
- Remove the remaining portion of the plastic cartridge. Invert the diluent bottle and penetrate the rubber seal on the concentrate bottle with the needle at an angle.
Alternate method of transferring sterile water: With a sterile needle and syringe, withdraw the appropriate volume of diluent and transfer to the bottle of lyophilized concentrate.
- Hold the diluent bottle at an angle to the concentrate bottle in order to direct the jet of diluent against the wall of the concentrate bottle. The vacuum will draw the diluent into the concentrate bottle. Avoid excessive foaming. Do not shake the concentrate bottle.
- After removing the diluent bottle and transfer-needle, optimal reconstitution time is achieved by swirling continuously until completely dissolved. Reconstitution can also be achieved by very gently agitating until dissolved.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
- After the concentrate powder is completely dissolved, withdraw the Factor IX Complex, Konyne (factor ix complex) ® 80 solution into the syringe through the filter needle which is supplied in the package. Replace the filter needle with an appropriate sterile injection needle, e.g., 21 gauge x 1 inch, and inject intravenously.
- If the same patient is to receive more than one bottle of Konyne (factor ix complex) 80, the contents of two bottles may be drawn into the same syringe through filter needles before attaching the vein needle.
Rate of Administration
The rate of administration should be adapted to the response of the individual patient, but is generally well-tolerated at a rate of approximately 100 IU per minute.
Factor IX Complex, Konyne® 80 is supplied in single dose bottles with the total IU of factor IX activity stated on the label of each bottle. A suitable volume of Sterile Water for Injection, USP, a sterile double-ended transfer needle, and a sterile filter needle are provided.
|0026-0626-20||500 IU||20 mL|
|0026-0626-50||1000 IU||40 mL|
Konyne (factor ix complex) 80 should be stored under refrigeration (2-8°C; 36-46°F). Freezing should be avoided as breakage of the diluent bottle might occur.
Konyne (factor ix complex) 80 concentrate may be stored for a period of up to 1 month at temperatures not to exceed 25°C (77°F) during travel.
U.S. federal law prohibits dispensing without prescription.
A number of factors beyond our control could reduce the efficacy of this product or even result in an ill effect following its use. These include improper storage and handling of the product after it leaves our hands, diagnosis, dosage, method of administration, and biological differences in individual patients. Because of these factors it is important that this product be stored properly, that the directions be followed carefully during use, and that the risk of transmitting viruses be carefully weighed before the product is prescribed.
No warranty, express or implied, including any warranty of merchantability or fitness is made. Representatives of the Company are not authorized to vary the terms or the contents of the printed labeling, including the package insert, for this product except by printed notice from the Company's headquarters. The prescriber and user of this product must accept the terms hereof.
- Johnson AJ, Aronson DL, Williams WJ: Preparation and clinical use of plasma and plasma fractions. In: Williams WJ (ed): Hematology, 4th ed, New York, McGraw-Hill, 1990, ch 170, pp 1659-1673.
- Zauber NP, Levin J: Factor IX levels in patients with hemophilia B (Christmas disease) following transfusion with concentrates of factor IX or fresh frozen plasma (FFP). Medicine (Baltimore) 56(3): 213-24, 1977.
- Mozen MM, Louie RE, Mitra G: Heat inactivation of viruses in antihemophilic factor concentrates. Abstracts, XVIth International Congress of the World Federation of Hemophilia, Rio de Janeiro, Aug. 24-28, 1984. Number 240.
- Feinstone SM, Alter HJ, Dienes HP, et al: Non-A, non-B hepatitis in chimpanzees and marmosets. J Infect Dis 144(6):588-98, 1981.
- Unpublished data in files of Bayer Corporation.
- Taberner DA, Thompson JM, Poller L: Comparison of prothrombin complex concentrate and vitamin K 1 in oral anticoagulant reversal. Br Med J 2(6027):83-5, 1976.
- Menache D, Roberts HR: Summary report and recommendations of the task force members and consultants. Thromb Diath Haemorrh 33:645-7, 1975.
- Aronson DL: Factor IX Complex. Semin Thromb Hemostas 6(1):28-43, 1979.
- Lusher JM, Shapiro SS, Palascak JE, et al: Efficacy of prothrombin-complex concentrates in hemophiliacs with antibodies to factor VIII: a multicenter therapeutic trial. N Engl J Med 303(8):421-5, 1980.
- Hoag MS, Johnson FF, Robinson AJ, et al: Treatment of hemophilia B with a new clotting-factor concentrate. N Engl J Med 280(11):581-6, 1969.
- Hoag MS, Johnson FF, Robinson AJ, et al: Use of plasma concentrate in congenital factor VII and IX deficiencies. Clin Res 17:152, 1969.
- Breen FA Jr, Tullis JL: Prothrombin concentrates in treatment of Christmas disease and allied disorders. JAMA 208(10):1848-52, 1969.
- Kasper CK: Postoperative thrombosis in hemophilia. N Engl J Med 289(3):160, 1973.
- Kasper CK: Surgical operation in hemophilia B. Use of factor IX concentrate. Calif Med 113(1):4-8, 1970.
- George JN, Breckenridge RT: The use of factor VIII and factor IX concentrates during surgery. JAMA 214(9):1673-6, 1970.
- Gunay U, Choi HS, Maurer HS, et al: Commercial preparations of prothrombin complex. A clinical comparison. Am J Dis Child 126(6):775-7, 1973.
- White GC 2d, Lundblad RL, Kingdon HS: Prothrombin complex concentrates: preparation, properties, and clinical uses. Curr Top Hematol 2:203-44, 1979.
- Colombo M, Mannucci PM, Carnelli V, et al: Transmission of non-A, non-B hepatitis by heat-treated factor VIII concentrate. Lancet 2(8445):1-4, 1985.
- National Hemophilia Foundation Medical and Scientific Advisory Council. Hemophilia Information Exchange AIDS Update: Recommendations concerning AIDS and the treatment of hemophilia. HIV infection, Section I.G. (Rev. Jan., 1988).
Last reviewed on RxList: 12/8/2004
This monograph has been modified to include the generic and brand name in many instances.
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