Reconstitution and Administration

Overview

Fabrazyme^® is administered by intravenous infusion. The initial infusion rate should be no more than 0.25 mg/min (15 mg/hour). After patient tolerance is well established, the infusion rate may be increased gradually with subsequent infusions; however, the total infusion time should not be less than 2 hours to minimize the potential occurrence of hypersensitivity reactions.

IMPORTANT: Make sure the patient is ready to receive treatment prior to reconstitution. Fabrazyme^® does not contain preservatives; therefore, it is recommended to start the administration of the diluted solution within three hours of reconstitution. The total time between reconstitution and completion of the infusion should not exceed 24 hours.

Patient Evaluation and Pre-treatment

1) Obtain the patient's weight and calculate the dose based on a mg/kg body weight basis.

2) Obtain the patient's baseline vital signs and blood work if needed.

3) Samples for possible antibody testing are advised to be taken at baseline, and at 6-month intervals after the date of the patient's first infusion.

4) As in the clinical trials, it is advised to administer antihistamines in combination with paracetamol or ibuprofen as pre-treatment one hour prior to the start of infusion (as of the first infusion).

Supplies and Equipment

Prepare a clean work area. Make sure all supplies and equipment necessary for reconstitution and administration of Fabrazyme are available. The following items are recommended for the reconstitution and administration of Fabrazyme:

Fabrazyme^®, 35 mg in single-use 20 ml glass vials

Water for Injections

0.9% Sodium Chloride 500 ml infusion bag/bottle

Syringes for reconstitution and dilution

Needles (without filtering devices)

Alcohol wipes

Intravenous (IV) giving set with flow-regulating device

Gloves

Tape

Supplies and equipment

Dosage Calculation

Verify the patient's current weight and calculate the number of vials needed to provide the recommended dosage of 1 mg/kg body weight. No dose adjustment is necessary for patients with renal insufficiency. Studies in patients with hepatic insufficiency have not been performed.

To calculate:
Patient's weight in kilograms/35 = number of vials to use

Preparation

1) Remove the appropriate number of vials from the refrigerator and allow them to reach room temperature. This takes approximately 20 minutes. Fabrazyme should always be stored between 2°C - 8°C.

2) Inspect each vial to ensure that it has not been compromised by particulate matter. Verify the expiration date on each vial. Do not use Fabrazyme after the expiration date.

3) Do not use filtering devices at any time during the preparation.

Reconstitution

1) Remove and discard plastic protective caps from vials. Clean vial tops with an alcohol wipe (Figure 1).

2) Using aseptic technique, reconstitute each vial with 7.2 ml of Water for Injections at room temperature. Inject the Water for Injections slowly against the inside wall of each vial (Figure 2). This yields a 5 mg enzyme/ml solution per vial. The reconstituted volume is 7.4 ml per vial.

3) Gently swirl each vial to mix (Figure 3). Avoid excessive agitation.

4) Let the solution stand until bubbles have dissipated and allow the lyophilised drug to thoroughly dissolve.

5) Visually inspect each vial. The solution should be clear. Do not use any vials that exhibit discoloration or particulate matter.

Figure 1

Figure 2

Figure 3

Dilution

1) The final total volume of the infusion should approximate 500 ml; therefore, prepare a 500 ml infusion bag/bottle of 0.9% Sodium Chloride at room temperature.

2) Clean port with alcohol wipe. Depending on the instructions given by the manufacturer of the bag/bottle, you may need first to remove from the infusion bag/bottle the quantity of 0.9% Sodium Chloride equal to the reconstituted volume of Fabrazyme so that the final volume approximates 500 ml (Figure 4).

3) Depending on the instructions given by the manufacturer of the bag/bottle, you may need to remove the overage from the infusion bag/bottle so that the final volume approximates 500 ml.

4) Slowly withdraw the reconstituted solution of Fabrazyme into a syringe until the dose is reached (Figure 5).

5) Clean port again with alcohol wipe. Slowly inject the dose of Fabrazyme into the bag/bottle of 0.9% Sodium Chloride. The final total volume should approximate 500 ml. Gently mix the bag/bottle and inspect for particulate matter.

Figure 4

Figure 5

Figure 6

Administration

1) Explain the administration procedure to the patient.

2) Connect the IV tubing to the bag/bottle of Fabrazyme (Figure 6).

3) Prime the IV tubing with 0.9% Sodium Chloride and expel any air. Do not allow excess fluid to drip from the end of the tubing.

4) The initial infusion rate should be no more than 0.25 mg/min (15 mg/hour). After patient tolerance is well established, the infusion rate may be increased gradually with subsequent infusions; however, the total infusion time should not be less than 2 hours to minimise the potential occurrence of hypersensitivity reactions.

5) Select the IV infusion site. The site will vary with the individual and may include antecubital, wrist or hand veins. A central venous catheter may also be used. Follow institutional procedures for IV insertion and medical infusion.

6) Attach the IV giving set and begin Fabrazyme infusion.

7) Monitor the infusion regularly.

8) Make sure all Fabrazyme is infused, including what is in the tubing. If it is not all infused, flush with the needed amount of 0.9% Sodium Chloride to ensure that all the Fabrazyme is delivered to the patient.

9) Remove the IV set and discard into an infectious waste container.

Important Safety Information

As with any intravenous protein products administered to "naïve" patients, patients receiving Fabrazyme^® may develop IgG antibodies to the product. The Phase III clinical trial data showed that seroconversion occurred in 88% of the patients treated with Fabrazyme^®. Patients with IgG antibodies to agalsidase beta may have higher risk of hypersensitivity reactions.

If a hypersensitivity reaction to Fabrazyme occurs during infusion, slow the infusion rate or consider stopping the infusion, immediately contact the attending physician and treat as directed. Report all adverse events promptly to Genzyme Belgium by completing an "Adverse Event Form" and fax it to +32 2 714 17 07.

You can also call at +32 2 714 17 11 or e-mail us

For complete safety information, please see the Summary of Product Characteristics.

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