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].
In clinical trials with ELAPRASE, 16/108 (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 anaphylatic 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.
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 5). 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 Use in Children and Use in Elderly under Precautions, Use in Pregnancy & Lactation and Adverse Reactions].
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.
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 [see Adverse Reactions].
Use in Children: Clinical trials with ELAPRASE were conducted in 96 patients with Hunter syndrome, ages 5 to 31 years old, with the majority of the patients in the pediatric age group (median age 15 years old). In addition, an open-label, uncontrolled clinical trial was conducted in 28 patients with Hunter syndrome, ages 16 months to 7.5 years old. Patients 16 months to 5 years of age demonstrated reduction in spleen volume that was similar to that of adults and children 5 years and older. However, there are no data to support improvement in disease-related symptoms or long term clinical outcome in patients 16 months to 5 years of age. [see Pharmacology: Pharmacodynamics: Clinical Studies under Actions].
The safety and effectiveness of ELAPRASE have not been established in pediatric patients less than 16 months of age.
Use in Elderly: Clinical studies of ELAPRASE did not include patients older than 31 years of age. It is not known whether older patients respond differently from younger patients.