Aldurazyme (Laronidase) - Indications and Dosage

INDICATIONS AND USAGE

ALDURAZYME is indicated for patients with Hurler and Hurler-Scheie forms of Mucopolysaccharidosis I (MPS I) and for patients with the Scheie form who have moderate to severe symptoms. The risks and benefits of treating mildly affected patients with the Scheie form have not been established.

ALDURAZYME has been shown to improve pulmonary function and walking capacity. ALDURAZYME has not been evaluated for effects on the central nervous system manifestations of the disorder.

INSTRUCTIONS FOR USE (ASEPTIC TECHNIQUES)

1. Determine the number of vials to be diluted based on the individual patient's weight and the recommended dose of 0.58 mg/kg [Patient's weight (kg) × 1 mL/kg of ALDURAZYME = Total # mL of ALDURAZYME, then Total # of mL of ALDURAZYME ÷ 5 mL per Vial = Total # of Vials]. Round up to the nearest whole vial. Remove the required number of vials from the refrigerator to allow them to reach room temperature. Do not heat or microwave vials.
2. Before withdrawing the ALDURAZYME from the vial, visually inspect each vial for particulate matter and discoloration. The ALDURAZYME solution should be clear to slightly opalescent and colorless to pale yellow. A few translucent particles may be present. Do not use if the solution is discolored or if there is particulate matter in the solution.
3. Determine the total volume of the infusion to be used based on the patient's body weight. The total final volume should be either 100 mL (if weight is less than or equal to 20 kg) or 250 mL (if weight is greater than 20 kg).
4. Using the chart below, prepare an infusion bag of 0.1% Albumin (Human) in 0.9% Sodium Chloride Injection, USP. Remove and discard a volume of 0.9% Sodium Chloride Injection, USP equal to the volume of Albumin (Human) to be added to the infusion bag. Add the appropriate volume of Albumin (Human) to the infusion bag and gently rotate the infusion bag to ensure proper distribution of the Albumin.

   Total Volume of ALDURAZYME Infusion	Volume of Albumin (Human) 5% to be Added	Volume of Albumin (Human) 25% to be Added
   100 mL	2 mL	0.4 mL
   250 mL	5 mL	1 mL

5. Withdraw and discard a volume of the 0.1% Albumin (Human) in 0.9% Sodium Chloride Injection, USP from the infusion bag, equal to the volume of ALDURAZYME concentrate to be added.
6. Slowly withdraw the calculated volume of ALDURAZYME from the appropriate number of vials using caution to avoid excessive agitation. Do not use a filter needle, as this may cause agitation. Agitation may denature ALDURAZYME, rendering it biologically inactive.
7. Slowly add the ALDURAZYME solution to the 0.1% Albumin (Human) in 0.9% Sodium Chloride Injection, USP using care to avoid agitation of the solutions. Do not use a filter needle.
8. Gently rotate the infusion bag to ensure proper distribution of ALDURAZYME. Do not shake the solution.

ALDURAZYME does not contain any preservatives, therefore after dilution with saline in the infusion bags, any unused product or waste material should be discarded and disposed of in accordance with local requirements.

ALDURAZYME must not be mixed with other medicinal products in the same infusion.

The compatibility of ALDURAZYME in solution with other products has not been evaluated.

STORAGE

Store ALDURAZYME under refrigeration at 2°C to 8°C (36°F to 46°F). DO NOT FREEZE OR SHAKE. DO NOT USE ALDURAZYME after the expiration date on the vial. This product contains no preservatives.

The diluted solution should be used immediately. If immediate use is not possible, the diluted solution should be stored refrigerated at 2°C to 8°C (36°F to 46°F). The in-use storage should not be longer than 36 hours from the time of preparation to completion of administration. Room temperature storage of diluted solution is not recommended.

DOSAGE AND ADMINISTRATION

The recommended dosage regimen of ALDURAZYME is 0.58 mg/kg of body weight administered once-weekly as an intravenous infusion.

Pretreatment with antipyretics and/or antihistamines is recommended 60 minutes prior to the start of the infusion (see PRECAUTIONS: General).

The total volume of the infusion is determined by the patient's body weight and should be delivered over approximately 3 to 4 hours. Patients with a body weight of 20 kg or less should receive a total volume of 100 mL. Patients with a body weight of greater than 20 kg should receive a total volume of 250 mL. The initial infusion rate of 10 mcg/kg/hr may be incrementally increased every 15 minutes during the first hour, as tolerated, until a maximum infusion rate of 200 mcg/kg/hr is reached. The maximum rate is then maintained for the remainder of the infusion (2-3 hours).

FOR PATIENTS WEIGHING 20 KG OR LESS

FOR PATIENTS WEIGHING GREATER THAN 20 KG

Each vial of ALDURAZYME provides 2.9 mg of laronidase in 5.0 mL of solution and is intended for single use only. Do not use the vial more than one time. The concentrated solution for infusion must be diluted with 0.1% Albumin (Human) in 0.9% Sodium Chloride Injection, USP using aseptic techniques. ALDURAZYME should be prepared using PVC Containers and administered with a PVC infusion set equipped with an in-line, low protein binding 0.2 micrometer (µm) filter. There is no information on the compatibility of diluted ALDURAZYME with glass containers.

HOW SUPPLIED

ALDURAZYME is supplied as a sterile solution in clear Type I glass 5 mL vials (2.9 mg laronidase per 5 mL). The closure consists of a siliconized butyl stopper and an aluminum seal with a plastic flip-off cap.

NDC 58468-0070-1

Rx Only

ALDURAZYME is manufactured by:

   BioMarin Pharmaceutical Inc.

   371 Bel Marin Keys Blvd.

   Suite 210

   Novato, CA 94949

   US License Number 1649

ALDURAZYME is distributed by:

   Genzyme Corporation

   One Kendall Square

   Cambridge, MA 02139

   1-800-745-4447 (phone)

ALDURAZYME is a registered trademark of BioMarin/Genzyme LLC.

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