The factor IX content is approximately 50 times purified over whole plasma, and when reconstituted as directed, Konyne 80 contains 25 times as much factor IX as an equal volume of fresh plasma. Konyne 80, containing approximately 1000 IU of factor IX administered in 40 mL, contains the factor IX content of 1 liter of fresh plasma. Konyne 80 must be administered intravenously.

Factors II, VII, IX and X are the vitamin K dependent coagulation factors and are synthesized in the liver. Congenital deficiencies of each of the four factors do occur and may result in a bleeding tendency. Naturally low levels of the vitamin K dependent factors may also be found in vitamin K deficiency and in severe liver disease.

This product has been heated at 80°C for 72 hours and there is no evidence of adverse effects upon the product. In a study ³ designed to assess the effectiveness of heat treatment at 68°C for 72 hours, hepatitis naive chimpanzees were inoculated with heated Antihemophilic Factor (Human) and Factor IX Complex preparations to which had been previously added non-A, non-B hepatitis Hutchinson Strain ⁴ to a total level of 2500 chimpanzee infectious doses (CID). The chimpanzees receiving heated preparations failed to exhibit any symptoms of non-A, non-B hepatitis. In contrast, one chimpanzee receiving Antihemophilic Factor (Human) concentrate which was not heated after the non-A, non-B inoculum was added, developed abnormally elevated alanine aminotransferase (ALT) levels beginning 10 weeks postinoculation and liver histopathology at 6 weeks. From these results, it was concluded that the heat treatment employed inactivated a known quantity of non-A, non-B hepatitis: at least 2500 CID.

Additional in vitro studies ⁵ on the effect of heating Factor IX Complex, Konyne® 80, in a dried state at 80°C for 72 hours, on virus inactivation were carried out with a number of viruses, including human immunodeficiency virus (HIV), added to Factor IX Complex prior to heating. The following table shows the amount of each model virus inactivated by the process:

Note: For publications on the clinical use of Konyne®, please refer to references 1,2, 6-17.

CONTRAINDICATIONS

PRECAUTIONS

General

Pregnancy Category C

Information for Patient

ADVERSE REACTIONS

DOSAGE AND ADMINISTRATION

The amount of Konyne 80 required for normalizing hemostasis will depend upon the patient and upon the circumstances. Sufficient Konyne 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:

Prophylaxis

Maintenance Dose

Inhibitor Patients

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

Reconstitution

Warm the unopened diluent and concentrate to room temperature (NMT 37°C, 99°F).
After removing the plastic flip-top caps (Fig. A) 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 (Fig. B).
Remove the remaining portion of the plastic cartridge. Invert the diluent bottle and penetrate the rubber seal on the concentrate bottle (Fig. C) 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 (Fig. D), optimal reconstitution time is achieved by swirling continuously until completely dissolved (Fig. E). 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® 80 solution into the syringe through the filter needle which is supplied in the package (Fig. F). Replace the filter needle with an appropriate sterile injection needle, e.g., 21 gauge × 1 inch, and inject intravenously.
If the same patient is to receive more than one bottle of Konyne 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.

HOW SUPPLIED

STORAGE

Konyne 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 80 concentrate may be stored for a period of up to 1 month at temperatures not to exceed 25°C (77°F) during travel.

CAUTION

LIMITED WARRANTY

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.