Control and Prevention of Bleeding Episodes

Kogenate® FS is an antihemophilic factor that is indicated for the control and prevention of bleeding episodes in adults and children (0-16 years) with hemophilia A.

Peri-operative Management

Kogenate FS is indicated for surgical prophylaxis in adults and children with hemophilia A.

Routine Prophylaxis in Children with Hemophilia A with No Pre-existing Joint Damage

Kogenate FS is indicated for routine prophylactic treatment to reduce the frequency of bleeding episodes and the risk of joint damage in children with no pre-existing joint damage.

Kogenate FS is not indicated for the treatment of von Willebrand's disease.

For Intravenous Use After Reconstitution

• Treatment with Kogenate FS should be initiated under the supervision of a physician experienced in the treatment of hemophilia A.
• Each vial of Kogenate FS has the recombinant factor VIII (rFVIII) potency in international units stated on the label.
• Dosage and duration of treatment depend on the severity of the factor VIII deficiency, the location and extent of bleeding, and the patient's clinical condition.¹ Careful control of replacement therapy is especially important in cases of major surgery or life-threatening bleeding episodes. [See Table 1 and Table 2.]

The expected in vivo peak increase in factor VIII level expressed as IU/dL (or % normal) can be estimated using the following formulas:

Dosage (units) = body weight (kg) x desired factor VIII rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL)

OR

IU/dL (or % normal)=Total Dose (IU)/body weight (kg) x 2 [IU/dL]/[IU/kg]

Examples (assuming patient's baseline factor VIII level is < 1% of normal):

1. A dose of 1750 IU Kogenate FS administered to a 70 kg patient should be expected to result in a peak post-infusion factor VIII increase of 1750 IU x {[2 IU/dL]/[IU/kg]}/[70 kg] = 50 IU/dL (50% of normal).
2. A peak level of 50% is required in a 15 kg child. In this situation, the appropriate dose would be: 50 IU/dL/{[2 IU/dL]/[IU/kg]} x 15 kg = 375 IU.

Doses administered should be titrated to the patient's clinical response. Patients may vary in their pharmacokinetic (e.g., half-life, in vivo recovery) and clinical responses to Kogenate FS.^2,3,4 Although the dose can be estimated by the calculations above, it is highly recommended that, whenever possible, appropriate laboratory tests including serial factor VIII activity assays be performed. [See WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY.]

Control and Prevention of Bleeding Episodes

The careful control of treatment dose is especially important in cases of life-threatening bleeding episodes or major surgery.

The following table can be used to guide dosing in bleeding episodes:

Table 1 : Control and Prevention of Bleeding Episodes for Children and Adults

Peri-operative Management

The careful control of treatment dose is especially important in cases of major surgery or life-threatening bleeding episodes.

The following table can be used to guide dosing in surgery:

Table 2 : Peri-operative Management for Adults and Children

Routine Prophylaxis in Children with No Pre-existing Joint Damage

The recommended dose for routine prophylaxis is 25 IU/kg of body weight every other day.⁵

Instructions for Use

Kogenate FS is administered by intravenous (IV) injection after reconstitution. Patients should follow the specific reconstitution and administration procedures provided by their physicians.

For instructions, patients should follow the recommendations in the FDA-Approved Patient Labeling. [See FDA-Approved Patient Labeling]

Reconstitution, product administration, and handling of the administration set and needles must be done with caution. Percutaneous puncture with a needle contaminated with blood can transmit infectious viruses including HIV (AIDS) and hepatitis. Obtain immediate medical attention if injury occurs. Place needles in a sharps container after single use. Discard all equipment, including any reconstituted Kogenate FS product, in an appropriate container.

Preparation and Reconstitution

The procedures below are provided as general guidelines for the reconstitution and administration of Kogenate FS.

Always work on a clean surface and wash hands before performing the following procedures.

Vacuum Transfer and Reconstitution

1. Warm the unopened diluent and the concentrate to a temperature not to exceed 37°C or 99°F.
2. After removing the plastic flip-top caps (Fig. A), aseptically cleanse the rubber stoppers of both vials with alcohol, being careful not to handle the rubber stopper.
3. Remove the protective cover from one end of the plastic transfer needle cartridge and penetrate the stopper of the diluent vial (Fig. B).
4. Remove the remaining portion of the protective cover, invert the diluent vial and penetrate the rubber seal on the concentrate vial (Fig. C) with the needle at an angle.
5. The vacuum will draw the diluent into the concentrate vial. Hold the diluent vial at an angle to the concentrate vial in order to direct the jet of diluent against the wall of the concentrate vial (Fig. C). Avoid excessive foaming. If the diluent does not get drawn into the vial, there is insufficient vacuum and the product should not be used.
6. After removing the diluent vial and transfer needle (Fig. D), swirl until completely dissolved without creating excessive foaming (Fig. E).
7. Re-swab top of reconstituted Kogenate FS vial with alcohol. Allow the stopper to air dry.
8. After the concentrate powder is completely dissolved, withdraw the solution into the syringe through the filter needle that is supplied in the package (Fig. F). Replace the filter needle with the administration set provided and inject intravenously. NOTE: See accompanying instructions for Infusion Set with Filter.
9. If the same patient is to receive more than one vial, the contents of two vials may be drawn into the same syringe through a separate unused filter needle before attaching the vein needle.
10. Kogenate FS should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Administration

For Intravenous Use Only After Reconstitution

• Kogenate FS should be inspected visually for particulate matter and discoloration prior to administration, wherever solution and container permit. Turbid or discolored solution should be discarded.
• Reconstituted Kogenate FS may be stored at room temperature prior to administration, but is to be administered within 3 hours. It is recommended to use the IV administration set provided.
• A dose of Kogenate FS may be administered over a period of 1 to 15 minutes. The rate of administration however, should be adapted to the response of each individual patient. The pulse rate should be determined before and during administration of Kogenate FS. If there is a significant increase in pulse rate, reducing the rate of administration or temporarily halting the injection allows the symptoms to disappear promptly.

Dosage Forms And Strengths

Kogenate FS is available as a lyophilized powder in single use glass vials containing 250, 500, 1000, 2000, and 3000 International Units (IU).

Each vial of Kogenate FS is labeled with the recombinant antihemophilic factor activity expressed in IU per vial. This potency assignment employs a factor VIII concentrate standard that is referenced to a WHO International Standard for factor VIII concentrates, and is evaluated by appropriate methodology to ensure accuracy of the results.

Kogenate FS is available as a kit in the following single use glass vial sizes. A suitable volume of Sterile Water for

Injection, USP, a double-ended transfer needle, a filter needle, and an administration set are provided in the kit.

Actual factor VIII activity in IU is stated on the label of each Kogenate FS Vial.

Storage and Handling

Product as Packaged for Sale:

• Store Kogenate FS at +2°C to +8°C (36°F to 46°F) for up to 30 months from the date of manufacture. Within this period, Kogenate FS may be stored for a period of up to 12 months at temperatures up to +25°C or 77°F, such as in home treatment situations.
• The starting date of room temperature storage should be clearly recorded on the unopened product carton. Once stored at room temperature, the product must not be returned to the refrigerator. The shelf-life then expires after the storage at room temperature, or the expiration date on the product vial, whichever is earlier.
• Do not use Kogenate FS after the expiration date indicated on the vial.
• Do not freeze.
• Protect from extreme exposure to light and store the lyophilized powder in the carton prior to use.

Product After Reconstitution

• Administer Kogenate FS within 3 hours after reconstitution.
• It is recommended to use the administration set provided.

REFERENCES

1. White GC, Rosendaal F, Aledort LM, Lusher JM, Rothschild C, Ingerslev J, for the Factor VIII and Factor IX Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definitions in hemophilia. Thromb Haemost 85:560-75, 2001.

2. Abildgaard CF, Simone JV, Corrigan JJ, et al: Treatment of hemophilia with glycine-precipitated Factor VIII. N Engl J Med 275(9):471–5, 1966.

3. Schwartz RS, Abildgaard CF, Aledort LM, et al: Human recombinant DNA-derived antihemophilic factor (factor VIII) in the treatment of hemophilia A. Recombinant Factor VIII Study Group. N Engl J Med 323(26):1800-5, 1990.

4. White GC 2nd, Courter S, Bray GL, et al: A multicenter study of recombinant factor VIII (Recombinate) in previously treated patients with hemophilia A. The Recombinate Previously Treated Patient Study Group.Thromb Haemost 77(4):660-667, 1997.

5. Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske B, Hacker MR, Kilcoyne R, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med 2007;357(6):535-44.

Kogenate FS Customer Service 1-888-606-3780. Bayer Reimbursement HELPline 1-800-288-8374. For more information, visit www.kogenatefs.com. Bayer HealthCare LLC Tarrytown, NY 10591 USA

Last reviewed on RxList: 6/11/2012
This monograph has been modified to include the generic and brand name in many instances.