ALDURAZYME [SIN13347P]

Product Info

ALDURAZYME

[SIN13347P]

INDICATIONS AND USAGE

ALDURAZYME (laronidase) 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.

DOSAGE AND ADMINISTRATION

Recommendations Prior to ALDURAZYME Treatment
Premedication
Prior to ALDURAZYME administration, consider premedicating with antihistamines, with or without antipyretics, 60 minutes before the start of infusion (see Warnings and Precautions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Medical Support
Appropriate medical monitoring and support measures, including cardiopulmonary resuscitation equipment, should be readily available during ALDURAZYME administration.

Recommended Dosage and Administration
The recommended dosage of ALDURAZYME is 0.58 mg/kg (actual body weight) administered once-weekly as an intravenous (IV) infusion. ALDURAZYME injection must be diluted with 0.9% Sodium Chloride Injection, to a final volume of 50 mL, 100 mL or 250 mL, as determined by the patient’s body weight and cardiopulmonary condition:
Patients with a body weight equal to or greater than 2 kg and less than 4 kg should receive a total volume of 50 mL. Patients with a body weight equal to or greater than 4 kg and up to 20 kg should receive a total volume of 100 mL; and those patients with a body weight greater than 20 kg should receive a total volume of 250 mL (see Administration Instructions). For patients with underlying cardiac or respiratory compromise and weighing up to 30 kg, physicians may consider diluting ALDURAZYME in a volume of 100 mL and administering at a decreased infusion rate (see Administration Instructions).

The initial infusion rate of ALDURAZYME is 10 mcg/kg/hr and may be increased every 15 minutes during the first hour, as tolerated, to a maximum infusion rate of 200 mcg/kg/hr. The maximum rate is then maintained for the remainder of the infusion (2 to 3 hours) (see Administration Instructions, Warnings and Precautions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

If one or more doses are missed, restart ALDURAZYME treatment as soon as possible and maintain the 1-week interval between infusions thereafter. Do not double a dose to compensate for a missed dose.

Administration Modifications due to Hypersensitivity or Infusion Associated Reaction
In the event of a severe hypersensitivity reaction (e.g. anaphylaxis) or severe infusion-associated reaction (IAR), immediately discontinue ALDURAZYME administration and initiate appropriate medical treatment. For additional recommendations in the event of a severe hypersensitivity reaction, see Warnings and Precautions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

In the event of a mild to moderate hypersensitivity reaction or a mild to moderate IAR, consider temporarily holding the infusion for 15 to 30 minutes, or slowing the infusion rate by 25% to 50% (see Administration Instructions), and initiating appropriate medical treatment (see Warnings and Precautions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

• If symptoms persist despite holding or slowing the infusion, stop the infusion and monitor the patient. Consider re-initiating the infusion within 7 to 14 days using the incremental rate steps table (see Administration Instructions), up to 25% or 50% of the rate at which the reaction occurred with appropriate premedication.

• If symptoms subside after holding the infusion, resume infusion at a 25% to 50% reduced rate as tolerated. Alternatively, if symptoms subside after slowing the infusion, complete infusion at the reduced rate as tolerated.

• Starting with next infusion, increase the infusion rate by increments of 25% as tolerated until the recommended infusion rate is reached. Closely monitor the patient.

Preparation Instructions

Prepare ALDURAZYME using low-protein-binding containers. There is no information on the compatibility of diluted ALDURAZYME with glass containers. Dilute ALDURAZYME in the following manner using aseptic technique:

1. Determine the infusion bag volume and number of ALDURAZYME vials to be diluted based on actual body weight in kg and the recommended dose (see Recommended Dosage and Administration).
   Round the number of vials up to the next whole number.

2. Remove the appropriate number of ALDURAZYME vials from the refrigerator and allow the vials to reach room temperature 20°C to 25°C (68°F to 77°F) before use. Do not heat or microwave the vials.

3. Visually inspect the solution in each vial for particulate matter and discoloration. The ALDURAZYME solution should be clear to slightly opalescent and colorless to pale yellow. Some translucency may be present in the solution. Discard if the solution is discolored or if visible particulate matter is present.

4. Withdraw and discard a volume of the 0.9% Sodium Chloride Injection from an infusion bag, equal to the volume of ALDURAZYME to be added.

5. 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. Discard any unused solution remaining in the vial.

6. Slowly add the ALDURAZYME solution to the 0.9% Sodium Chloride Injection, solution through the port of the infusion bag and avoid agitation. Do not use a filter needle.

7. Gently rotate the infusion bag to ensure proper distribution of ALDURAZYME. Do not shake the infusion bag.

Storage Instruction for the Diluted Solution
If the diluted ALDURAZYME solution is not used immediately:

• Refrigerate the diluted solution at 2°C to 8°C (36°F to 46°F) for up to 36 hours. Discard any unused ALDURAZYME diluted solution after 36 hours. Do not store the diluted solution at room temperature.

• The solution must be infused within 8 hours after removal from the refrigerator, inclusive of the total infusion time, or discarded.

Administration Instructions

1. Use an infusion set equipped with a low-protein-binding 0.2 micron in-line filter to administer the diluted ALDURAZYME solution.

2. The total volume of infusion (see Recommended Dosage and Administration) should be administered over approximately 3 to 4 hours as tolerated per the infusion rate steps outlined in Table 3 below.

3. At the end of the infusion, flush the infusion line with 0.9% Sodium Chloride Injection, using the same infusion rate as the one used for the last part of the infusion.

4. Do not infuse ALDURAZYME in the same intravenous line with other products.

Start infusion at rate in Step 1. In the absence of infusion-associated reactions after vital sign assessment, increase infusion rate sequentially per the steps in Table 1 every 15 minutes to reach the target rate in Step 5. Continue Step 5 until infusion is completed. The total infusion time is approximately 3 to 4 hours.

CONTRAINDICATIONS

None.