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ALDURAZYME (laronidase) Solution for intravenous
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use ALDURAZYME safely and effectively. See full prescribing information for ALDURAZYME.
ALDURAZYME (laronidase)
Solution for intravenous infusion only
Initial U.S. Approval: 2003
WARNING: RISK OF ANAPHYLAXIS.
See full prescribing information for complete boxed warning.
Life-threatening anaphylactic reactions have been observed in some patients during ALDURAZYME infusions. Therefore, appropriate medical support should be readily available when ALDURAZYME is administered. Patients with compromised respiratory function or acute respiratory disease may be at risk of serious acute exacerbation of their respiratory compromise due to infusion reactions, and require additional monitoring.
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
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0.58 mg/kg of body weight administered once weekly as an intravenous (IV) infusion (2).
DOSAGE FORMS AND STRENGTHS
Solution: 2.9 mg/5 mL vial (3).
CONTRAINDICATIONS
None (4)
WARNINGS AND PRECAUTIONS
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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).
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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).
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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).
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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
A registry for pregnant women is available. Pregnant women with MPS I should be encouraged to enroll in the MPS I Registry. For more information, visit www.MPSIregistry.com or call (800) 745-4447 (8.1).
See 17 for PATIENT COUNSELING INFORMATION.
Revised: 4/2013
FULL PRESCRIBING INFORMATION: CONTENTS*
1 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 eva luated for effects on the central nervous system manifestations of the disorder.
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dose
The recommended dosage regimen of ALDURAZYME is 0.58 mg/kg of body weight administered once weekly as an intravenous (IV) infusion. Pretreatment is recommended 60 minutes prior to the start of the infusion and may include antihistamines, antipyretics, or both [see Warnings and Precautions (5)].
Each vial of ALDURAZYME provides 2.9 milligrams (mg) of laronidase in 5.0 milliliters (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 0.9% Sodium Chloride Injection, USP, to a final volume of 100 mL or 250 mL, using aseptic techniques. The final volume of the infusion is determined by the patient’s body weight. Patients with a body weight of 20 kg or less should receive a total volume of 100 mL. Patients with a body weight greater than 20 kg should receive a total volume of 250 mL [see Dosage and Administration (2.2)]. 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 Dosage and Administration (2.2), Warnings and Precautions (5.3) and Adverse Reactions (6.3)].
2.2 Instructions for Use
Prepare and use ALDURAZYME according to the following steps. Use aseptic techniques. Prepare ALDURAZYME using low-protein-binding containers and administer with a low-protein-binding 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.
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Determine the number of vials to be diluted based on the patient's weight and the recommended dose of 0.58 mg/kg, using the following equation:
Patient's weight (kg) x 1 mL/kg of ALDURAZYME = Total number mL of ALDURAZYME
Total number mL of ALDURAZYME ÷ 5 mL per Vial = Total number of Vials.
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Round up to the next whole vial. Remove the required number of vials from the refrigerator to allow them to reach room temperature. Do not heat or microwave vials.
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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. Some translucency may be present in the solution. Do not use if the solution is discolored or if there is particulate matter in the solution.
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Withdraw and discard a volume of the 0.9% Sodium Chloride Injection, USP from the infusion bag, equal to the volume of ALDURAZYME concentrate to be added.
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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.
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Slowly add the ALDURAZYME solution to the 0.9% Sodium Chloride Injection, USP using care to avoid agitation of the solutions. Do not use a filter needle.
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Gently rotate the infusion bag to ensure proper distribution of ALDURAZYME. Do not shake the solution.
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The entire infusion volume (100 mL for patients weighing 20 kg or less and 250 mL for patients weighing greater than 20 kg) should be delivered over approximately 3 to 4 hours. The initial infusion rate of 10 µg/kg/hr may be incrementally increased every 15 minutes during the first hour, as tolerated, until a maximum infusion rate of 200 µg/kg/hr is reached. The maximum rate is then maintained for the remainder of the infusion (2-3 hours), as outlined in Tables 1 and 2.
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Administer the diluted ALDURAZYME solution to patients using a low-protein-binding infusion set equipped with a low-protein-binding 0.2 µm in-line filter.
ALDURAZYME does not contain any preservatives; therefore, after dilution with saline, the infusion bags should be used immediately. If immediate use is not possible, the diluted solution should be stored refrigerated at 2° to 8°C (36° to 46°F) for up to 36 hours. Other than during infusion, room temperature storage of diluted solution is not recommended. Any unused product or waste material should be discarded and disposed of in accordance with local requirements.
ALDURAZYME must not be administered with other medicinal products in the same infusion. The compatibility of ALDURAZYME in solution with other products has not been eva luated.
3 DOSAGE FORMS AND STRENGTHS
ALDURAZYME is supplied as a sterile solution in 5 mL vials (2.9 mg per 5 mL).
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Anaphylaxis and Allergic Reactions
[see Boxed Warning ]
Anaphylaxis and severe allergic reactions have been observed in patients during or up to 3 hours after ALDURAZYME infusions. Some of these reactions were life-threatening and included respiratory failure, respiratory distress, stridor, tachypnea, bronchospasm, obstructive airways disorder, hypoxia, hypotension, bradycardia, and urticaria. If anaphylactic or other severe allergic reactions occur, immediately discontinue the infusion of ALDURAZYME and initiate appropriate medical treatment. Caution should be exercised if epinephrine is being considered for use in patients with MPS I due to the increased preva lence of coronary artery disease in these patients. Interventions have included resuscitation, mechanical ventilatory support, emergency tracheotomy, hospitalization, and treatment with inhaled beta-adrenergic agonists, epinephrine, and IV corticosteroids [see Adverse Reactions (6)].
In clinical studies and postmarketing safety experience with ALDURAZYME, approximately 1% of patients experienced severe or serious allergic reactions. In patients with MPS I, pre-existing upper airway obstruction may have contributed to the severity of some reactions. Due to the potential for severe allergic reactions, appropriate medical support should be readily available when Aldurazyme is administered. Because of the potential for recurrent reactions, some patients who experience initial severe reactions may require prolonged observation.
The risks and benefits of re-administering ALDURAZYME following an anaphylactic or severe allergic reaction should be considered. Extreme care should be exercised, with appropriate resuscitation measures available, if the decision is made to re-administer the product.
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