Elaprase Special Precautions

Hypersensitivity Reactions Including Anaphylaxis: Serious hypersensitivity reactions, including anaphylaxis, have occurred during and up to 24 hrs 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. Biphasic anaphylactic reactions have also been reported to occur after administration of Elaprase approximately 24 hrs after treatment and recovery from an initial anaphylactic reaction that occurred during Elaprase infusion. Interventions for biphasic reactions have included hospitalization and treatment with epinephrine, inhaled β-adrenergic agonists and corticosteroids.
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). With these measures, no patient discontinued treatment permanently due to an allergic reaction.
In clinical trials with Elaprase, 16 of 108 (15%) patients experienced hypersensitivity reactions during 26 of 8274 (0.3%) infusions that involved adverse events in at least 2 of the following 3 body systems: Cutaneous, respiratory or cardiovascular. Of these 16 patients, 11 experienced significant anaphylactic reactions during 19 of 8274 (0.2%) infusions with symptoms of bronchospasm, cyanosis, dyspnea, erythema, edema (facial and peripheral), flushing, rash, respiratory distress, urticaria, vomiting and wheezing.
In post-marketing 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 2-4 month time period. Medical management included treatment with antihistamines, inhaled β-adrenergic agonists, corticosteroids, oxygen and vasopressors. Treatment was discontinued for some patients, while others continued treatment with premedication and a slower infusion rate.
Because of 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 post-marketing reports. Inform patients of the signs and symptoms of anaphylaxis, and instruct them to seek immediate medical care should signs and symptoms occur. Because of the potential for biphasic anaphylactic reactions after Elaprase administration, patients who experience initial severe or refractory reactions may require prolonged observation.
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 ≤7 years, 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 Ab development than Hunter syndrome patients with missense mutations. Eleven (11) of 15 (73%) patients with complete gene deletion, large gene rearrangement, nonsense, frameshift or splice site mutations and 5 of 12 (42%) patients with missense mutations experienced hypersensitivity reactions. Nine (9) of 15 (60%) patients with complete gene deletion, large gene rearrangement, nonsense, frameshift or splice site mutations and 2 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) Ab, compared to only 3 patients with missense mutations (see Table 5). Thirteen (13) patients with these mutations developed NAbs, which interfere with Elaprase uptake into the cell or Elaprase enzyme activity, compared to only 1 patient with missense mutation (see Hypersensitivity Reactions Including Anaphylaxis in the previous texts 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 in patients with concomitant acute respiratory and/or febrile illness. One (1) patient with a tracheostomy and severe airway disease, who received an Elaprase infusion while he had a preexisting febrile illness, experienced respiratory distress, hypoxia, cyanosis and seizure with loss of consciousness.
If a severe reaction occurs, immediately suspend the infusion of Elaprase and initiate appropriate treatment, depending on the severity of the symptoms. Consider resuming the infusion at a slower rate, or, if the reaction is serious enough to warrant it, discontinue the Elaprase infusion for that visit.
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).
Carcinogenicity, Mutagenicity & Impairment of Fertility: Long-term studies in animals to evaluate carcinogenic potential or studies to evaluate mutagenic potential have not been performed with Elaprase.
Elaprase at IV doses up to 5 mg/kg, administered twice weekly (about 1.6 times the recommended human weekly dose based on body surface area) had no effect on fertility and reproductive performance in male rats.
Use in pregnancy: Pregnancy Category C: Teratogenicity studies have not been conducted with Elaprase. A pre- and postnatal development study in rats showed no evidence of adverse effects on pre- and postnatal development at IV doses up to 12.5 mg/kg, administered twice weekly (about 4 times the recommended human weekly dose of 0.5 mg/kg based on body surface area). There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Elaprase should be used during pregnancy only if clearly needed.
Use in lactation: Elaprase was excreted in breast milk of lactating rats at a concentration higher (4- to 5-fold) than that of the plasma. It is not known whether Elaprase is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Elaprase is administered to a nursing woman.
Use in children: Clinical trials with Elaprase were conducted in 96 patients with Hunter syndrome, ages 5-31 years, with the majority of the patients in the pediatric age group (median age 15 years). In addition, an open-label, uncontrolled clinical trial was conducted in 28 patients with Hunter syndrome, ages 16 months-7.5 years. Patients 16 months-5 years demonstrated reduction in spleen volume that was similar to that of adults and children ≥5 years. However, there are no data to support improvement in disease-related symptoms or long-term clinical outcome in patients 16 months-5 years (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions). The safety and effectiveness of Elaprase have not been established in pediatric patients <16 months.
Use in the elderly: Clinical studies of Elaprase did not include patients >31 years. It is not known whether geriatric patients respond differently from younger patients.