Version May 2024
Life-threatening anaphylactic reactions have occurred in some patients during and up to 24 hours after idursulfase infusions. Anaphylaxis, presenting as respiratory distress, hypoxia, hypotension, urticaria, and/or angioedema of throat or tongue, has been reported to occur during and after idursulfase infusions, regardless of duration of the course of treatment. Closely observe patients during and after administration and be prepared to manage anaphylaxis. Inform patients of the signs and symptoms of anaphylaxis and have them seek immediate medical care should symptoms occur. Patients with compromised respiratory function or acute respiratory disease may be at risk of serious acute exacerbation of their respiratory compromise due to hypersensitivity reactions, and require additional monitoring.
Mucopolysaccharidosis type II (MPS II, Hunter syndrome): Note: Current consensus opinion recommends initiation of therapy as early as possible following diagnosis (Scarpa 2011):
Children 16 months to <5 years: Limited data available: IV: 0.5 mg/kg once weekly (Muenzer 2011; Scarpa 2011). A small, open-labeled evaluation of the safety and efficacy of 53 weeks of therapy in 28 pediatric patients ≤5 years of age showed enzyme replacement with idursulfase reduced splenic volume similar to older pediatric patients but data did not support improvement in other disease-related symptoms (which were undefined) or long-term clinical outcomes (which were undefined) (manufacturer's labeling). Proving clinical benefit of therapy for disease-related symptoms in this population is challenging due to age-related compliance with evaluation techniques (eg, walking capacity evaluations, FEV) (Muenzer 2011). A larger observation trial (n=124) of patients <6 years (including infants) showed weekly administration of idursulfase produced a significant decrease in hepatic volume and a reduction in urine glycosaminoglycans (GAG) levels similar to that in older pediatric patients (Muenzer 2011).
Children ≥5 years and Adolescents: IV: 0.5 mg/kg once weekly.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Idursulfase: Drug information")
Mucopolysaccharidosis II (Hunter syndrome): IV: 0.5 mg/kg once weekly.
There are no dosage adjustments provided in the manufacturer’s labeling.
There are no dosage adjustments provided in the manufacturer’s labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Flushing (7% to 16%)
Central nervous system: Headache (28%), fatigue (13%)
Dermatologic: Skin rash (19% to 32%), pruritus (25%), urticaria (16%)
Gastrointestinal: Vomiting (5% to 14%)
Hypersensitivity: Hypersensitivity reaction (57% to 69%)
Immunologic: Antibody development (neutralizing: 41% to 79%), development of IgG antibodies (51% to 68%)
Neuromuscular & skeletal: Musculoskeletal pain (13%)
Otic: Otitis (children: 11%)
Respiratory: Pneumonia (children: 18%)
Miscellaneous: Fever (9% to 36%)
1% to 10%:
Cardiovascular: Tachycardia (9%), hypotension (5%)
Central nervous system: Chills (9%), dizziness (5%)
Dermatologic: Erythema (7%)
Gastrointestinal: Diarrhea (9%), nausea (5%)
Respiratory: Cough (9%)
Frequency not defined:
Cardiovascular: Cardiac arrhythmia, pulmonary embolism
Hypersensitivity: Angioedema
Infection: Infection
<1%, postmarketing, and/or case reports: Anaphylaxis, cyanosis, loss of consciousness, respiratory distress, respiratory failure, seizure
There are no contraindications listed in the manufacturer’s labeling.
Canadian labeling: Hypersensitivity to idursulfase or any component of the formulation
Concerns related to adverse effects:
• Hypersensitivity/anaphylactoid reactions: [US Boxed Warning]: Serious hypersensitivity reactions, including fatal life-threatening anaphylactic reactions, have been reported during and within 24 hours after infusion. Anaphylaxis may present as respiratory distress, hypoxia, hypotension, urticaria, and/or tongue/throat angioedema. Monitor closely during and after infusion. Appropriate medical support should be readily available. Patients with compromised respiratory function or acute respiratory disease are at risk of respiratory disease exacerbation due to hypersensitivity; additional monitoring may be required. Discontinue immediately if anaphylactic or acute reaction occurs. Patients experiencing initial severe or refractory reactions may need prolonged monitoring. Antihistamines, corticosteroids and/or decreased infusion rates may be used to manage subsequent infusions.
• Antibody formation: Development of anti-idursulfase IgG antibodies has been reported in 51% of patients; may increase incidence of hypersensitivity reactions.
Disease-related concerns:
• Acute febrile/respiratory illness: Hypersensitivity reactions may occur. Use caution and consider delaying treatment in patients with compromised respiratory function or acute febrile or respiratory illness; may be at increased risk for life-threatening complications from hypersensitivity reactions.
• Fluid overload: Use with caution in patients at risk for fluid overload or in conditions where fluid restriction is indicated (eg, acute underlying respiratory illness, compromised cardiac and/or respiratory function); conditions may be exacerbated during infusion. Extended observation may be necessary for some patients.
• Genetic mutations: Use with caution in patients with severe genetic mutations (eg, complete gene deletion, large gene rearrangement, nonsense, frameshift or splice site mutations); may increase risk of hypersensitivity reactions, serious adverse reactions, and antibody development.
Other warnings/precautions:
• Registry: Patients and healthcare providers are encouraged to participate in the Hunter Outcome Survey, intended to monitor disease progression, patient outcomes, and long-term effects of therapy. For more information, refer to www.elaprase.com or call OnePathsm at 1-866-888-0660.
When compared to pediatric patients >7 years, the patients ≤7 years of age were shown to have more frequent development of anti-idursulfase IgG antibodies (68% vs 51%) and neutralizing antibodies (79% vs 41%). In patients <5 years of age, an association between the presence of antibodies and reduced systemic idursulfase exposure has been observed; this has not been reported in older pediatric patients (≥5 years of age). Younger pediatric patients have also been shown to develop neutralizing antibodies earlier in therapy (at week 9 vs 27) and at higher titers.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Elaprase: 6 mg/3 mL (3 mL)
No
Solution (Elaprase Intravenous)
6 mg/3 mL (per mL): $1,254.33
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Elaprase: 6 mg/3 mL (3 mL)
IV: Administer using an infusion set containing a 0.2 micron low protein-binding inline filter. Infuse at an initial rate of 8 mL/hour for the first 15 minutes. If tolerated, may increase rate by 8 mL/hour increments every 15 minutes up to maximum infusion rate of 100 mL/hour. Rate may be decreased, temporarily stopped, or discontinued based on tolerance. Initial infusion should be over 3 hours; if tolerated, subsequent infusions may be gradually reduced to a 1-hour infusion. Total infusion time should not exceed 8 hours. Note: For subsequent doses, current guidelines suggest that shortened infusion time of 1 hour is not desirable and increased the risk of infusion-related reaction; extra precautions should be used (Scarpa 2011).
IV: Administer using an infusion set containing a 0.2 micron low protein-binding inline filter. Infuse at an initial rate of 8 mL/hour for the first 15 minutes. If tolerated, may increase rate by 8 mL/hour increments every 15 minutes; maximum infusion rate of up to 100 mL/hour. Rate may be decreased, temporarily stopped, or discontinued based on tolerance. Initial infusion should be over 3 hours; if tolerated, subsequent infusions may be gradually reduced to a 1-hour infusion. Total infusion time should not exceed 8 hours.
Store vials under refrigeration at 2°C to 8°C (36°F to 46°F). Protect from light, do not freeze or shake. Should be used immediately after dilution in NS. However, solution for infusion may be stored under refrigeration for up to 24 hours.
Replacement therapy in mucopolysaccharidosis II (MPS II, Hunter syndrome) (FDA approved in ages ≥5 years and adults).
Elaprase may be confused with Elspar
None known.
There are no known significant interactions.
Adverse events were not observed in animal reproduction studies.
Monitor for infusion-related and hypersensitivity reactions; pulmonary function, oxygen saturation; blood pressure.
Idursulfase is a recombinant form of iduronate-2-sulfatase, an enzyme needed to hydrolyze the mucopolysaccharides dermatan sulfate and heparan sulfate in various cells. Accumulation of these polysaccharides can lead to various manifestations of disease, including physical changes, CNS involvement, cardiac, respiratory, and mobility dysfunction. Replacement of this enzyme has been shown to improve walking capacity in patients with a deficiency.
Distribution: Varies dependent upon age and presence of antibodies (particularly patients <7.5 years): Vss:
Children 16 months to <7.5 years: Week 1: 394 ± 423 mL/kg; Week 27: Antibody negative: 272 ± 112 mL/kg; antibody positive: 829 ± 636 mL/kg
Children ≥7.5 years, Adolescents, and Adults <27 years: Mean range: 213 to 254 mL/kg
Half-life elimination: Varies dependent upon age and presence of antibodies (particularly patients <7.5 years)
Children 16 months to <7.5 years: Week 1: 160 ± 69 minutes; Week 27: Antibody negative: 134 ± 19 minutes; antibody positive: 84 ± 46 minutes
Children ≥7.5 years, Adolescents, and Adults <27 years: Mean range: 44 to 48 minutes
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