Helixate 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. Helixate 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 product HELIXATE, 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 an be determined only by clinical response, and by monitoring circulating FVIII levels after treatment (see DOSAGE AND ADMINISTRATION). Because Helixate FS has similar biological activity to HELIXATE it can be used in the same manner.

Helixate FS does not contain von Willebrands factor and therefore is not indicated for the treatment of von Willebrands disease

Each bottle of Helixate 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 Helixate 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 Helixate® 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 products^7-9 and is illustrated in the following examples:

Expected % factor VIII increase =          # units administered X 2%/IU/kg 
                                                                     --------------------------------------------
                                                                                      body weight (kg)

Example for a 70 kg adult:                                   1400 IU X 2%/IU/kg
                                                                      --------------------------------------------              = 40%
                                                                                              70(kg)

or

Dosage required (IU) =                    body weight kg x desired % FVIII increase
                                                                    -------------------------------------------
                                                                                          2%/IU/kg

Example for a 15 kg child:                                         15 kg X 100%
                                                                                    --------------------------               = 750 IU required
                                                                                            2%/IU/kg

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

Prophylaxis

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

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 Helixate® FS 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 Helixate 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:

a) One-hand technique: Hold tubing in hand and advance needle shield with thumb and index finger until locked over needle tip (Fig. G).

b) 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.

Helixate® 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.

STORAGE

Helixate 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.

CAUTION
Rx only

REFERENCES

6.   Kasper CK: Complications of hemophilia A treatment: factor VIII inhibitors. Ann NY Acad Sci 614:97-105,1991.

7.   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.

8.   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.

9.   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.

10.  Nilsson IM, Berntorp E, Löfqvist T, et al: Twenty-five years experience of prophylactic treatment in severe haemophilia A and B. J Intern Med232(1):25-32,1992.

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