Idursulfase

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous [preservative free]:

Elaprase: 6 mg/3 mL (3 mL)

Pharmacology

Mechanism of Action

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.

Pharmacokinetics/Pharmacodynamics

Distribution

Varies dependent upon age and presence of antibodies (particularly patients <7.5 years): V_ss:

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

Use: Labeled Indications

Mucopolysaccharidosis II (Hunter syndrome): Enzyme replacement therapy in Hunter syndrome (mucopolysaccharidosis II; MPS II)

Contraindications

There are no contraindications listed in the manufacturer’s labeling.

Canadian labeling: Hypersensitivity to idursulfase or any component of the formulation

Dosage and Administration

Dosing: Adult

Mucopolysaccharidosis II (Hunter syndrome): IV: 0.5 mg/kg once weekly

Dosing: Pediatric

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)

Children ≥5 years and Adolescents: IV: 0.5 mg/kg once weekly

Reconstitution

Allow vials to reach room temperature prior to preparation. Dilute dose in NS 100 mL. Mix gently, do not shake.

Administration

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.

Storage

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.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

>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

Warnings/Precautions

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 OnePath^sm at 1-866-888-0660.

Monitoring Parameters

Monitor for infusion-related and hypersensitivity reactions; pulmonary function, oxygen saturation; blood pressure

Pregnancy

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience loss of strength and energy, headache, diarrhea, muscle pain, cough, or itching. Have patient report immediately to prescriber signs of infusion reaction, severe dizziness, passing out, blue/gray skin discoloration, shortness of breath, severe nausea, vomiting, seizures, chills, flushing, or fast heartbeat (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.