Idursulfase

Idursulfase
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rabin Bista, M.B.B.S. [2]

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Black Box Warning

WARNING: See full prescribing information for complete Boxed Warning. RISK OF ANAPHYLAXIS: Life-threatening anaphylactic reactions have occurred in some patients during and up to 24 hours after ELAPRASE infusions. Anaphylaxis, presenting as respiratory distress, hypoxia, hypotension, urticaria and/or angioedema of throat or tongue have been reported to occur during and after ELAPRASE infusions, regardless of duration of the course of treatment. Closely observe patients during and after ELAPRASE 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

Overview

Idursulfase is a hydrolytic lysosomal glycosaminoglycan (GAG)-specific enzyme that is FDA approved for the treatment of Hunter syndrome (Mucopolysaccharidosis II, MPS II). There is a Black Box Warning for this drug as shown here. Common adverse reactions include headache, pruritus, musculoskeletal pain, urticaria, diarrhea, cough, pyrexia, rash, vomiting.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Indications

ELAPRASE is indicated for patients with Hunter syndrome (Mucopolysaccharidosis II, MPS II). ELAPRASE has been shown to improve walking capacity in patients 5 years and older.

In patients 16 months to 5 years of age, no data are available to demonstrate improvement in disease-related symptoms or long term clinical outcome; however, treatment with ELAPRASE has reduced spleen volume similarly to that of adults and children 5 years of age and older.

The safety and efficacy of ELAPRASE have not been established in pediatric patients less than 16 months of age

Dosage

The recommended dosage regimen of ELAPRASE is 0.5 mg per kg of body weight administered once weekly as an intravenous infusion.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

3 DOSAGE FORMS AND STRENGTHS Injection: 6 mg/3 mL (2 mg/mL) in single-use vials

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Idursulfase in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Idursulfase in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Indications

ELAPRASE is indicated for patients with Hunter syndrome (Mucopolysaccharidosis II, MPS II). ELAPRASE has been shown to improve walking capacity in patients 5 years and older.

In patients 16 months to 5 years of age, no data are available to demonstrate improvement in disease-related symptoms or long term clinical outcome; however, treatment with ELAPRASE has reduced spleen volume similarly to that of adults and children 5 years of age and older.

The safety and efficacy of ELAPRASE have not been established in pediatric patients less than 16 months of age

Dosage

The recommended dosage regimen of ELAPRASE is 0.5 mg per kg of body weight administered once weekly as an intravenous infusion.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Idursulfase in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Idursulfase in pediatric patients.

Contraindications

• None

Warnings

WARNING: See full prescribing information for complete Boxed Warning. RISK OF ANAPHYLAXIS: Life-threatening anaphylactic reactions have occurred in some patients during and up to 24 hours after ELAPRASE infusions. Anaphylaxis, presenting as respiratory distress, hypoxia, hypotension, urticaria and/or angioedema of throat or tongue have been reported to occur during and after ELAPRASE infusions, regardless of duration of the course of treatment. Closely observe patients during and after ELAPRASE 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

Hypersensitivity Reactions Including Anaphylaxis Serious hypersensitivity reactions, including anaphylaxis, have occurred during and up to 24 hours after infusion. Some of these reactions were life-threatening and included respiratory distress, hypoxia, hypotension, urticaria, and angioedema of the throat or tongue, regardless of duration of the course of treatment.

If anaphylactic or other acute reactions occur, immediately discontinue the infusion of ELAPRASE and initiate appropriate medical treatment. When severe reactions have occurred during clinical trials, subsequent infusions were managed with antihistamine and/or corticosteroids prior to or during infusions, a slower rate of ELAPRASE infusion, and/or early discontinuation of the ELAPRASE infusion [see ADVERSE REACTIONS (6)].

In clinical trials with ELAPRASE, 16 of 108 (15%) patients experienced hypersensitivity reactions during 26 of 8,274 infusions (0.3%) that involved adverse events in at least two of the following three body systems: cutaneous, respiratory, or cardiovascular. Of these 16 patients, 11 experienced anaphylactic reactions during 19 of 8,274 infusions (0.2%) with symptoms of bronchospasm, cyanosis, dyspnea, erythema, edema (facial and peripheral), flushing, rash, respiratory distress, urticaria, vomiting, and wheezing.

In postmarketing reports, patients receiving ELAPRASE experienced anaphylactic reactions up to several years after initiating treatment. Some patients were reported to have repeated anaphylactic events over a two- to four-month time period. Medical management included treatment with antihistamines, inhaled beta-adrenergic agonists, corticosteroids, oxygen, and vasopressors. Treatment was discontinued for some patients, while others continued treatment with premedication and a slower infusion rate.

Due to the potential for severe reactions, appropriate medical support should be readily available when ELAPRASE is administered. Observe patients closely for an appropriate period of time after administration of ELAPRASE, taking into account the time to onset of anaphylaxis seen in premarketing clinical trials and postmarketing reports. Inform patients of the signs and symptoms of anaphylaxis, and instruct them to seek immediate medical care should signs and symptoms occur.

5.2 Risk of Hypersensitivity, Serious Adverse Reactions, and Antibody Development in Hunter Syndrome Patients with Severe Genetic Mutations In the clinical trial of Hunter syndrome patients aged 7 years and younger, patients with complete gene deletion, large gene rearrangement, nonsense, frameshift or splice site mutations experienced a higher incidence of hypersensitivity reactions, serious adverse reactions and anti-idursulfase antibody development than Hunter syndrome patients with missense mutations. Eleven of 15 (73%) patients with complete gene deletion, large gene rearrangement, nonsense, frameshift or splice site mutations and five of 12 (42%) patients with missense mutations experienced hypersensitivity reactions. Nine of 15 (60%) patients with complete gene deletion, large gene rearrangement, nonsense, frameshift or splice site mutations and two of 12 (17%) patients with missense mutations had serious adverse reactions. All 15 patients with complete gene deletion, large gene rearrangement, nonsense, frameshift or splice site mutations developed anti-idursulfase (ELAPRASE) antibodies, compared to only 3 patients with missense mutations (Table 2). Thirteen patients with these mutations developed neutralizing antibodies, which interfere with ELAPRASE uptake into the cell or ELAPRASE enzyme activity, compared to only one patient with missense mutation [see WARNINGS AND PRECAUTIONS (5.1), ADVERSE REACTIONS (6.1, 6.2) and USE IN SPECIFIC POPULATIONS (8.4)].

5.3 Risk of Acute Respiratory Complications Patients with compromised respiratory function or acute febrile or respiratory illness at the time of ELAPRASE infusion may be at higher risk of life-threatening complications from hypersensitivity reactions. Careful consideration should be given to the patient's clinical status prior to administration of ELAPRASE and consider delaying the ELAPRASE infusion. One patient with a tracheostomy, severe airway disease and acute febrile illness experienced respiratory distress, hypoxia, cyanosis, and seizure with a loss of consciousness during ELAPRASE infusion.

5.4 Risk of Acute Cardiorespiratory Failure Caution should be exercised when administering ELAPRASE to patients susceptible to fluid overload, or patients with acute underlying respiratory illness or compromised cardiac and/or respiratory function for whom fluid restriction is indicated. These patients may be at risk of serious exacerbation of their cardiac or respiratory status during infusions. Appropriate medical support and monitoring measures should be readily available during ELAPRASE infusion, and some patients may require prolonged observation times that should be based on the individual needs of the patient

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Clinical Trial Experience of Idursulfase in the drug label.

Body as a Whole

Cardiovascular

Digestive

Endocrine

Hematologic and Lymphatic

Metabolic and Nutritional

Musculoskeletal

Neurologic

Respiratory

Skin and Hypersensitivy Reactions

Special Senses

Urogenital

Miscellaneous

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Idursulfase in the drug label.

Body as a Whole

Cardiovascular

Digestive

Endocrine

Hematologic and Lymphatic

Metabolic and Nutritional

Musculoskeletal

Neurologic

Respiratory

Skin and Hypersensitivy Reactions

Special Senses

Urogenital

Miscellaneous

Drug Interactions

• Drug

• Description

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

• Pregnancy Category

Pregnancy Category (AUS):

• Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Idursulfase in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Idursulfase during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Idursulfase with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Idursulfase with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Idursulfase with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Idursulfase with respect to specific gender populations.

Race

There is no FDA guidance on the use of Idursulfase with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Idursulfase in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Idursulfase in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Idursulfase in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Idursulfase in patients who are immunocompromised.

Administration and Monitoring

Administration

Preparation Instructions Prepare and use ELAPRASE according to the following steps using aseptic technique:

Determine the total volume of ELAPRASE to be administered and the number of vials needed based on the patient's weight and the recommended dose of 0.5 mg/kg.

Round up to the next whole vial to determine the total number of vials needed. Remove the required number of vials from the refrigerator to allow them to reach room temperature. Before withdrawing the ELAPRASE solution from the vial, visually inspect each vial for particulate matter and discoloration. The ELAPRASE solution should be clear to slightly opalescent and colorless. Do not use if the solution is discolored or if there is particulate matter in the solution. Do not shake the ELAPRASE solution. Withdraw the calculated volume of ELAPRASE from the appropriate number of vials. Add the calculated volume of ELAPRASE solution to a 100 mL bag of 0.9% Sodium Chloride Injection, USP for intravenous infusion. Mix gently. Do not shake the solution. 2.3 Administration Instructions Administer the diluted ELAPRASE solution to patients using a low-protein-binding infusion set equipped with a low-protein-binding 0.2 micrometer (µm) in-line filter.

The total volume of infusion should be administered over a period of 3 hours, which may be gradually reduced to 1 hour if no hypersensitivity reactions are observed. Patients may require longer infusion times if hypersensitivity reactions occur; however, infusion times should not exceed 8 hours. The initial infusion rate should be 8 mL per hour for the first 15 minutes. If the infusion is well tolerated, the rate of infusion may be increased by 8 mL per hour increments every 15 minutes. The infusion rate should not exceed 100 mL per hour. The infusion rate may be slowed, temporarily stopped, or discontinued for that visit in the event of hypersensitivity reactions [see WARNINGS AND PRECAUTIONS (5.1)]. ELAPRASE should not be infused with other products in the infusion tubing.

2.4 Storage and Stability ELAPRASE does not contain 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°C to 8°C (36°F to 46 °F) for up to 24 hours. Other than during infusion, do not store the diluted ELAPRASE solution at room temperature. Any unused product or waste material should be discarded and disposed of in accordance with local requirements.

Monitoring

There is limited information regarding Monitoring of Idursulfase in the drug label.

• Description

IV Compatibility

There is limited information regarding IV Compatibility of Idursulfase in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

• Description

Management

• Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Idursulfase in the drug label.

Pharmacology

There is limited information regarding Idursulfase Pharmacology in the drug label.

Mechanism of Action

Structure

File:Idursulfase01.png

This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Idursulfase in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Idursulfase in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Idursulfase in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Idursulfase in the drug label.

How Supplied

Storage

There is limited information regarding Idursulfase Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Idursulfase in the drug label.

Precautions with Alcohol

• Alcohol-Idursulfase interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• ®

Look-Alike Drug Names

• A® — B®

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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