Reconstitution and Administration

1. Myozyme™ vials
2. Water for Injection
3. 0.9% Sodium Chloride Injection
4. Syringes for reconstitution and dilution
5. Needles (do not use filter needles during preparation)
6. Intravenous administration set
7. In-line low protein-binding 0.2 μm filter
8. Additional supplies per institution’s IV infusion protocol

Note: Make sure the patient is ready to receive treatment before reconstituting the enzyme. Myozyme™ does not contain preservatives and should not be stored for subsequent use once reconstituted.

1. The dose of Myozyme™ is based on the patient’s weight. The recommended dosage is 20 milligrams per kilogram (mg/kg) of body weight, infused every 2 weeks as an intravenous infusion. The number of 50 mg vials required is based on the patient’s body weight and the prescribed dose.

2. Remove Myozyme™ vials from the refrigerator and allow the vials to reach room temperature prior to reconstitution (approximately 30 minutes). DO NOT USE Myozyme™ after the expiration date on the vial.

3. Prepare a clean work area and organize necessary supplies and equipment for preparation and administration.

1. Remove and dispose of plastic protective caps from vials. Prepare the vials for reconstitution using aseptic technique.

2. Reconstitute each Myozyme™ vial by slowly injecting 10.3 ml of Water for Injection to the inside wall of each vial. Avoid forceful impact of the water on the powder to minimize foaming. This is done by slow drop-wise addition of the water for injection down the inside of the vial and not directly onto the lyophilized cake. Tilt and roll each vial gently. Do not invert, swirl or shake.

3. Visually inspect the reconstituted vials. The vials should contain a clear, colorless to pale yellow solution. The reconstituted solution may also contain a few particles in the form of thin white strands or clear fibers.

4. Prepare Myozyme™ in the appropriate size 0.9% Sodium Chloride for Injection infusion bag according to the suggested infusion volumes. The recommended final concentration of Myozyme™ in the infusion bags ranges from 0.5 to 4mg/ml. Remove airspace from the infusion bag. This has been shown to reduce agitation and minimize the formation of protein particles.

5. Slowly withdraw the reconstituted solution from each vial avoiding foaming within the syringe. Further dilute with the appropriate volume of 0.9 % Sodium Chloride Injection. Prepare the appropriate volume by removing sufficient 0.9% Sodium Chloride from a pre-filled bag. Be sure to inject the reconstituted Myozyme™ solution directly into the sodium chloride solution rather than into air that may remain within the infusion bag to minimize agitation and the potential for the formation of protein particles. Dispose of any vial with unused reconstituted solution.

6. Gently massage the infusion bag to mix the diluted solution. Avoid vigorous shaking and agitation to minimize the formation of particles. Visually inspect the infusion solution. The solution should appear clear and colorless but may contain a few protein particles in the form of thin white strands or clear fibers. Do not use infusion solution that contains any foreign matter, or if the solution is discolored. Label the infusion bag per your institution’s procedures. Hand-carry the infusion bag to the end user. Do not use a pneumatic tube delivery system.

7. The final infusion should be filtered through an in-line low protein-binding 0.2 μm filter during administration. If visible protein particles are present in the final solution they will be removed via in-line filtration with no apparent loss of protein or activity.

8. Myozyme™ should not be infused in the same intravenous line with other products.

1. The recommended dosage regimen of Myozyme™ is 20 mg/kg body weight administered every 2 weeks as an intravenous infusion.

In clinical trials pre-treatment medications were used but not routinely administered to patients.

Infusions should be administered in a step-wise manner. Use of an infusion pump will provide an accurate infusion rate.

The infusion should be filtered through an in-line low protein-binding 0.2 μm filter during administration to remove any visible protein particles.

It is recommended that the infusion begin at an initial rate of 1 mg/kg/hr and be increased by 2 mg/kg/hr every 30 minutes, if well tolerated, until a maximum rate of 7 mg/kg/hr is reached.

The infusion time is typically 3½ to 4 hours for any patient at a dose of 20 mg/kg.

2. Careful consideration should be given to the patient’s clinical status before administration. Explain the procedure to the patient or caregiver.

3. Obtain IV access. Antecubital, wrist, hand veins, or central line may be used for access.

4. Connect the IV tubing to the Myozyme™ infusion bag.

5. Prime the tubing with Myozyme™ and remove any air before the administration.

6. Attach IV tubing and begin Myozyme™ infusion.

7. During the infusion, monitor the patient carefully.

8. Patients may choose to read, watch television, or use the rest room during the infusion.

9. The following interventions have effectively managed infusion associated reactions in most cases during clinical trials with Myozyme™: reducing the infusion rate, temporarily interrupting the infusion and/or treatment with oral antihistamine and/or antipyretics.

10. If severe hypersensitivity or anaphylactic reactions occur, immediate discontinuation of the administration of Myozyme™ should be considered and appropriate medical treatment should be initiated.

11. When the infusion is complete, flush the tubing, at the last infusion rate, with 0.9% Sodium Chloride Injection to infuse any residual Myozyme™ in the tubing.

1. Follow your institution’s policy for IV insertion and medication infusion.

2. Infusion reactions can occur. If an infusion reaction occurs, decreasing the infusion rate, temporarily stopping the infusion, and/or administration of additional antipyretics, antihistamines and/or steroids may ameliorate the symptoms.

3. Please report any Adverse Event to Genzyme’s Pharmacovigilance Department at + 31 35 699 1299 or EU-Pharmacovigilance@genzyme.com

Please see the Summary of Product Characteristics (SmPC) (PDF) for full prescribing information in Dutch or French for Myozyme^TM.