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Kogenate (Antihemophilic Factor (Recombinant)) - Indications and Dosage

 
 



INDICATIONS AND USAGE

Kogenate FS is indicated for the treatment of classical hemophilia (hemophilia A) in which there is a demonstrated deficiency of activity of the plasma clotting factor FVIII. Kogenate FS provides a means of temporarily replacing the missing clotting factor in order to correct or prevent bleeding episodes, or in order to perform emergency or elective surgery in hemophiliacs.

In clinical studies with the predecessor productKOGENATE, some patients who developed inhibitors on study continued to manifest a clinical response when inhibitor titers were less than 10 Bethesda Units (BU) per mL. When an inhibitor is present, the dosage requirement for FVIII is variable. The dosage can be determined only by clinical response, and by monitoring circulating FVIII levels after treatment (see DOSAGE AND ADMINISTRATION). Because Kogenate FS has similar biological activity toKOGENATE it can be used in the same manner.

Kogenate FS does not contain von Willebrand's factor and therefore is not indicated for the treatment of von Willebrand's disease.

INSTRUCTIONS FOR USE

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 Antihemophilic Factor (Recombinant) product, in accordance with biohazard procedures.

RECONSTITUTION

Always wash your hands before performing the following procedures:

VACUUM TRANSFER

  1. Warm the unopened diluent and the concentrate to a temperature not to exceed 37°C, 99°F.
  2. After removing the plastic flip-top caps (Fig. A), aseptically cleanse the rubber stoppers of both bottles 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 bottle (Fig. B).
  4. Remove the remaining portion of the protective cover, invert the diluent bottle and penetrate the rubber seal on the concentrate bottle (Fig. C) with the needle at an angle.
  5. The vacuum will draw the diluent into the concentrate bottle. 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 (Fig. C). Avoid excessive foaming. If the diluent does not get drawn into the bottle, there is insufficient vacuum and the product should not be used.
  6. After removing the diluent bottle and transfer needle (Fig. D), swirl until completely dissolved without creating excessive foaming (Fig. E).
  7. Re-swab top of reconstituted Kogenate FS bottle with alcohol. Allow the stopper to air dry.
  8. After the concentrate powder is completely dissolved, withdraw 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: Firmly grasp one or both wings to perform venipuncture; do not use the post-use needle shield for this purpose.
  9. After infusion, lock post-use needle shield in place using one of the following methods:
    1. One-hand technique: Hold tubing in hand and advance needle shield with thumb and index finger until locked over needle tip (Fig. G).
    2. Two-hand technique: Hold wing stationary and slide needle shield forward with other hand until locked over needle tip (Fig. H).
  10. If the same patient is to receive more than one bottle, the contents of two bottles may be drawn into the same syringe through a separate unused filter needle before attaching the vein needle.
  11. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

RATE OF ADMINISTRATION

The rate of administration should be adapted to the response of the individual patient, but administration of the entire dose in 5 to 10 minutes or less is well tolerated.

DOSAGE AND ADMINISTRATION

Each bottle of Kogenate FS has the rFVIII potency in international units stated on the label based on the one-stage assay methodology. The reconstituted product must be administered within 3 hours after reconstitution. It is recommended to use the administration set provided.

GENERAL APPROACH TO TREATMENT AND ASSESSMENT OF TREATMENT EFFICACY

The dosages described below are presented as general guidance. It should be emphasized that the dosage of Kogenate FS required for hemostasis must be individualized according to the needs of the patient, the severity of the deficiency, the severity of the hemorrhage, the presence of inhibitors, and the FVIII level desired. It is often critical to follow the course of therapy with FVIII level assays. The clinical effect of FVIII is the most important element in evaluating the effectiveness of treatment. It may be necessary to administer more FVIII than estimated in order to attain satisfactory clinical results. If the calculated dose fails to attain the expected FVIII levels, or if bleeding is not controlled after administration of the calculated dosage, the presence of a circulating inhibitor in the patient should be suspected. Its presence should be substantiated and the inhibitor level quantitated by appropriate laboratory tests. When an inhibitor is present, the dosage requirement for FVIII could be extremely variable among different patients, and the optimal treatment can be determined only by the clinical response.

Some patients with low-titer inhibitors (< 10 BU) can be successfully treated with FVIII preparations without a resultant anamnestic rise in inhibitor titer.6 FVIII levels and clinical response to treatment must be assessed to insure adequate response. Use of alternative treatment products, such as Factor IX Complex concentrates, Antihemophilic Factor (Porcine), recombinant Factor VIIa or Anti-Inhibitor Coagulant Complex, may be necessary for patients with anamnestic responses to FVIII treatment and/or high-titer inhibitors.

CALCULATION OF DOSAGE

The in vivo percent elevation in FVIII level can be estimated by multiplying the dose of Kogenate® FS Antihemophilic Factor (Recombinant) per kilogram of body weight (IU/kg) by 2% per IU per kg. This method of calculation is based on clinical findings with the use of plasma-derived and recombinant AHF products7-9 and is illustrated in the following examples:

Expected % factor VIII increase = # units administered × 2%/IU/kg
body weight (kg)
        
Example for a 70 kg adult: 1400 IU × 2%/IU/kg
70 kg
= 40%
or   
Dosage required (IU) = body weight (kg) × desired % FVIII increase
2%/IU/kg
                
Example for a 15 kg child: 15 kg×100%
2%/IU/kg
= 750 IU required
  

The dosage necessary to achieve hemostasis depends upon the type and severity of the bleeding episode, according to the following general guidelines:

Hemorrhagic event Therapeutically necessary plasma level of FVIII activity Dosage necessary to maintain the therapeutic plasma level
Minor hemorrhage
(superficial, early hemorrhages, hemorrhages into joints)
20-40% 10-20 IU per kg Repeat dose if evidence of further bleeding.
Moderate to major hemorrhage (hemorrhages into muscles, hemorrhages into the oral cavity, definite hemarthroses, known trauma) 30-60% 15-30 IU per kg Repeat one dose at 12-24 hours if needed.
Surgery (minor surgical procedures)     
Major to life-threatening hemorrhage (intracranial, intraabdominal or intrathoracic hemorrhages, gastrointestinal bleeding, central nervous system bleeding, bleeding in the retropharyngeal or retroperitoneal spaces, or iliopsoas sheath) 80-100% Initial dose
40-50 IU per kg
Repeat dose
20-25 IU per kg every 8-12 hours.
Fractures Head trauma      
Surgery
Major surgical procedures
~100% Preoperative dose 50 IU/kg
Verify ~100% activity prior to surgery. Repeat as necessary after 6 to 12 hours initially, and for 10 to 14 days until healing is complete.

Prophylaxis

AHF concentrates may also be administered on a regular schedule for prophylaxis of bleeding, as reported by Nilsson et al.10

HOW SUPPLIED

Kogenate® FS Antihemophilic Factor (Recombinant) is supplied in the following single use bottles. A suitable volume of Sterile Water for Injection, USP, a sterile double-ended transfer needle, a sterile filter needle, and a sterile administration set are provided.

NDC Number Approximate FVIII Activity (IU) Diluent (mL)
0026-0372-20 250 2.5
0026-0372-30 500 2.5
0026-0372-50 1000 2.5

STORAGE

Kogenate FS should be stored under refrigeration (2-8°C; 36-46°F). Freezing must be avoided. Do not use beyond the expiration date indicated on the bottle. Protect from extreme exposure to light and store the lyophilized powder in the carton prior to use.

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