RECENT MAJOR CHANGES

Dosage and Administration, Recommended Dose (2.1)07/2011
Dosage and Administration, Instructions for Use (2.2)07/2011
Warnings and Precautions, Anaphylaxis and Allergic
Reactions (5.1)07/2011
Warnings and Precautions, Acute Respiratory Complications
Associated with Administration (5.2)07/2011
Warnings and Precautions, Risk of Acute Cardiorespiratory
Failure (5.3)07/2011
Warnings and Precautions, Infusion Reactions (5.4)07/2011

INDICATIONS AND USAGE

ALDURAZYME is a hydrolytic lysosomal glycosaminoglycan (GAG)-specific enzyme 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 eva luated for effects on the central nervous system manifestations of the disorder (1).

DOSAGE AND ADMINISTRATION

• 0.58 mg/kg of body weight administered once weekly as an intravenous (IV) infusion (2).

DOSAGE FORMS AND STRENGTHS

Solution for IV infusion: 2.9 mg/5 mL vial (3).

CONTRAINDICATIONS

None (4)

WARNINGS AND PRECAUTIONS

• Anaphylaxis and Allergic Reactions:Life-threatening anaphylactic reactions have been observed in some patients during ALDURAZYME infusion and up to 3 hours after infusion. Appropriate medical support and monitoring measures should be readily available when ALDURAZYME is administered. If anaphylactic or other severe allergic reactions occur, immediately discontinue the infusion and initiate appropriate treatment, which may include ventilatory support, treatment with inhaled beta-adrenergic agonists, epinephrine, and IV corticosteroids (5.1).
• Risk of Acute Respiratory Complications:Patients with acute febrile or respiratory illness at the time of ALDURAZYME infusion may be at greater risk for infusion reactions. Consider delaying ALDURAZYME infusion. Sleep apnea is common in MPS I patients. eva luation of airway patency should be considered prior to initiation of treatment with ALDURAZYME. Appropriate respiratory support should be available during infusion (5.2).
• Risk of Acute Cardiorespiratory Failure: Caution should be exercised when administering ALDURAZYME to patients susceptible to fluid overload. Consider a decreased total infusion volume and infusion rate when administering ALDURAZYME to these patients. Appropriate medical monitoring and support measures should be available during infusion (2.2, 5.3).
• Infusion Reactions: Pretreatment is recommended prior to the infusion to reduce the risk of infusion reactions and may include antihistamines, antipyretics, or both. If infusion reactions occur, decreasing the infusion rate, temporarily stopping the infusion, or administering additional antipyretics and/or antihistamines may ameliorate the symptoms (5.4).

ADVERSE REACTIONS

The most commonly reported infusion reactions occurring in at least 10% of patients 6 months of age and older were pyrexia, chills, blood pressure increased, tachycardia, and oxygen saturation decreased (6). The most frequently occurring adverse reactions occurring in at least 10% of patients 6 years and older are rash, upper respiratory tract infection, injection site reaction, hyperreflexia, paresthesia, flushing, and poor venous access.

To report SUSPECTED ADVERSE REACTIONS, contact: Genzyme at 1-800-745-4447, or FDA at 1-800-FDA-1088 or go to www.fda.gov/medwatch.

USE IN SPECIFIC POPULATIONS