Elaprase

Elaprase

idursulfase

Manufacturer:

Sanofi

Distributor:

DCH Auriga - Healthcare
Full Prescribing Info
Contents
Idursulfase.
Description
Each vial contains extractable volume of 3 mL with an idursulfase concentration of 2 mg/mL at a pH of approximately 6, providing idursulfase 6 mg, sodium chloride 24 mg, monobasic sodium phosphate monohydrate 6.75 mg, dibasic sodium phosphate heptahydrate 2.97 mg and polysorbate 20 0.66 mg.
Elaprase does not contain preservatives and is for single use only.
Elaprase is a formulation of idursulfase, a purified form of human iduronate-2-sulfatase, a lysosomal enzyme. Idursulfase is produced by recombinant DNA technology in a human cell line. Idursulfase is an enzyme that hydrolyzes the 2-sulfate esters of terminal iduronate sulfate residues from the glycosaminoglycans (GAG) dermatan sulfate and heparan sulfate in the lysosomes of various cell types.
Idursulfase is a 525-amino acid glycoprotein with a molecular weight of approximately 76 kilodaltons. The enzyme contains 8 asparagine-linked glycosylation sites occupied by complex oligosaccharide structures. The enzyme activity of idursulfase is dependent on the post-translational modification of a specific cysteine to formylglycine. Idursulfase has a specific activity ranging from protein 46-74 u/mg (1 unit is defined as the amount of enzyme required to hydrolyze 1 micromole of heparin disaccharide substrate per hour under the specified assay conditions).
Action
Pharmacology: Pharmacodynamics: Decreases in urinary GAG levels were observed following treatment with Elaprase. The responsiveness of urinary GAG to dosage alterations of Elaprase is unknown, and the relationship of urinary GAG to other measures of clinical response has not been established. Patients who tested positive for anti-idursulfase antibodies (Ab) experienced a less pronounced decrease in urinary GAG levels (see Clinical Studies as follows and Adverse Reactions).
Mechanism of Action: Hunter syndrome (mucopolysaccharidosis II, MPS II) is an X-linked recessive disease caused by insufficient levels of the lysosomal enzyme iduronate-2-sulfatase. This enzyme cleaves the terminal 2-O-sulfate moieties from the GAG dermatan sulfate and heparan sulfate. Due to the missing or defective iduronate-2-sulfatase enzyme in patients with Hunter syndrome, GAG progressively accumulate in the lysosomes of a variety of cells, leading to cellular engorgement, organomegaly, tissue destruction and organ system dysfunction.
Treatment of Hunter syndrome patients with Elaprase provides exogenous enzyme for uptake into cellular lysosomes. Mannose-6-phosphate (M6P) residues on the oligosaccharide chains allow specific binding of the enzyme to the M6P-receptors on the cell surface, leading to cellular internalization of the enzyme, targeting to intracellular lysosomes and subsequent catabolism of accumulated GAG.
Clinical Studies: Clinical Trials in Patients ≥5 Years: The safety and efficacy of Elaprase were evaluated in a 53-week, randomized, double-blind, placebo-controlled clinical trial of 96 patients with Hunter syndrome. The trial included patients with a documented deficiency in iduronate-2-sulfatase enzyme activity who had a percent-predicted forced vital capacity (percent-predicted FVC) <80%. The patients' ages ranged from 5-31 years. Patients who were unable to perform the appropriate pulmonary function testing or those who could not follow protocol instructions were excluded from the study. Patients received Elaprase 0.5 mg/kg every week (n=32), Elaprase 0.5 mg/kg every other week (n=32) or placebo (n=32).
The primary efficacy outcome assessment was a 2-component composite score based on the sum of the ranks of the change from baseline to week 53 in distance walked during a 6-min walk test (6-MWT) and the ranks of the change in percent-predicted FVC. This 2-component composite primary endpoint differed statistically significantly between the 3 groups, and the difference was greatest between the placebo group and the once weekly treatment group (once weekly Elaprase vs placebo, p=0.0049).
Examination of the individual components of the composite score showed that, in the adjusted analysis, the weekly Elaprase-treated group experienced a 35-m greater mean increase in the distance walked in 6 min compared to placebo. The changes in percent-predicted FVC were not statistically significant. (See Table 1.)

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Pharmacodynamic assessments included urinary GAG levels and changes in liver and spleen size. Urinary GAG levels were elevated in all patients at baseline. Following 53 weeks of treatment, mean urinary GAG levels were markedly reduced in the Elaprase once-weekly group, although GAG levels still remained above the upper limit of normal in half of the Elaprase-treated patients. Urinary GAG levels remained elevated and essentially unchanged in the placebo group. Sustained reductions in both liver and spleen volumes were observed in the Elaprase once-weekly group through week 53 compared to placebo. There were essentially no changes in liver and spleen volumes in the placebo group.
Extension Trial: Patients who participated in the placebo-controlled trial were eligible to continue treatment in an open-label extension trial. During the extension trial, all patients received Elaprase 0.5 mg/kg once-weekly for 24 months.
Patients who were treated with Elaprase once weekly and every other week in the placebo-controlled trial demonstrated improvement in distance walked in the 6-MWT for an additional 8 months of treatment in the extension trial. There was no change in mean percent-predicted FVC in all Hunter syndrome patients after 6 months of treatment in the extension trial; however, a slight decrease in mean percent-predicted FVC was demonstrated through to month 24 of the extension trial. The long-term effect of Elaprase on pulmonary function in Hunter syndrome patients is unclear.
There were no further reductions in mean urinary GAG levels in patients initially treated with Elaprase once weekly; however, the patients treated with Elaprase every other week during the placebo-controlled trial experienced further reductions in mean urinary GAG levels after changing to a more frequent dosing regimen during the extension trial. The persistence of reduced urinary GAG levels did not correlate with the long term effect demonstrated by the 6-MWT distance or percent-predicted FVC.
Clinical Trial in Patients ≤7 Years: A 53-week, open-label, multicentre, single-arm trial was conducted to assess the safety, pharmacokinetics and pharmacodynamics of Elaprase 0.5 mg/kg once weekly in male Hunter syndrome patients ≤7 years. Safety results demonstrated that patients with complete gene deletion or large gene rearrangement mutations are more likely to develop Ab, including neutralizing antibodies (NAbs), and to experience hypersensitivity reactions with Elaprase administration (see Adverse Reactions). In patients who remained Ab-negative, the pharmacokinetic profile, reduction in urinary GAG excretion levels and reduction in spleen volume were similar to those of adults and children ≥5 years. In patients who were persistently Ab-positive, the presence of anti-idursulfase antibody was associated with reduced systemic exposure of idursulfase and a less pronounced decrease in urinary GAG levels (see Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions).
Pharmacokinetics: CLinical Trials in Patients ≥5 Years: The pharmacokinetic characteristics of idursulfase were evaluated in 59 patients with Hunter syndrome. The serum concentration of idursulfase was quantified using an antigen-specific enzyme-linked immunosorbent assay (ELISA). The area under the concentration-time curve (AUC) increased in a greater than dose proportional manner as the dose increased from 0.15-1.5 mg/kg following a single 1-hr infusion of Elaprase. The pharmacokinetic parameters at the recommended dose regimen (Elaprase 0.5 mg/kg administered weekly as a 3-hr infusion) were determined at weeks 1 and 27 in 10 patients 7.7-27 years (see Table 2). There were no apparent differences in pharmacokinetics parameter values between weeks 1 and 27 regardless of the Ab status in these patients.

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Clinical Trial in Patients ≤7 Years: Idursulfase pharmacokinetics was evaluated in 27 patients with Hunter syndrome 16 months-7.5 years who received Elaprase 0.5 mg/kg once weekly as a 3-hr infusion. The presence of anti-idursulfase Ab was associated with a reduced systemic exposure of idursulfase. Eight (8) of the 18 Ab-positive patients had no measurable idursulfase concentrations. An additional 9 Ab-positive patients had decreased peak plasma concentration (Cmax), AUC and half-life (t½) at week 27 compared to week 1 (see Table 3). Idursulfase pharmacokinetics was similar between weeks 1 and 27 in Ab-negative patients (see Table 3).

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All patients with the complete gene deletion or large gene rearrangement genotype (n=8) developed Ab at week 27. Five (5) of these 8 patients had no measurable idursulfase concentrations at week 27, and 3 had a lower systemic exposure at week 27 compared to week 1.
Indications/Uses
Patients with Hunter syndrome (Mycopolysaccharidosis II, MPS II). Elaprase has been shown to improve walking capacity in patients ≥5 years.
In patients 16 months to 5 years, 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.
The safety and efficacy of Elaprase have not been established in pediatric patients <16 months (see Precautions).
Dosage/Direction for Use
The recommended dosage regimen of Elaprase is 0.5 mg/kg of body weight administered every week as an IV infusion.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Administration: Administer the diluted Elaprase solution to patients using a low-protein-binding infusion set equipped with a low-protein-binding 0.2 micrometer in-line filter.
The total volume of infusion may be administered over a period of 3 hrs, which may be gradually reduced to 1 hr if no hypersensitivity reactions are observed. Patients may require longer infusion times if hypersensitivity reactions occur; however, infusion times should not exceed 8 hrs. The initial infusion rate should be 8 mL/hr for the first 15 min. If the infusion is well tolerated, the rate may be increased by 8 mL/hr increments at 15-min intervals in order to administer the full volume within the desired period of time. However, at no time should the infusion rate exceed 100 mL/hr. The infusion rate may be slowed and/or temporarily stopped, or discontinued for that visit, based on clinical judgment, if hypersensitivity reactions were to occur (see Warnings).
Overdosage
One (1) patient with Hunter syndrome, who received Elaprase at twice the recommended dosage for 1½ year, experienced 2 anaphylactic reactions over a 3-month period 4.5 years after initiating Elaprase treatment.
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.
Use In Pregnancy & Lactation
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.
Adverse Reactions
Clinical Trials Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The following serious adverse reactions are described as follows and elsewhere in the labeling:
Hypersensitivity Reactions Including Anaphylaxis (see Warnings): In clinical trials, the most common adverse reactions (>10%) following Elaprase treatment were hypersensitivity reactions, and included rash, urticaria, pruritus, flushing, pyrexia and headache. Most hypersensitivity reactions requiring intervention were ameliorated with slowing of the infusion rate, temporarily stopping the infusion, with or without administering additional treatments including antihistamines, corticosteroids or both prior to or during infusions.
In clinical trials, the most frequent serious adverse reactions following Elaprase treatment were hypoxic episodes. Other notable serious adverse reactions that occurred in the Elaprase-treated patients but not in the placebo-treated patients included 1 case each of: Cardiac arrhythmia, pulmonary embolism, cyanosis, respiratory failure, infection and arthralgia.
Clinical Trials in Patients ≥5 Years: A 53-week, double-blind, placebo-controlled clinical trial of Elaprase was conducted in 96 male patients with Hunter syndrome, ages 5-31 years. Of the 96 patients, 83% were White, non-Hispanic. Patients were randomized to 3 treatment groups, each with 32 patients: Elaprase 0.5 mg/kg once weekly, Elaprase 0.5 mg/kg every other week or placebo. Hypersensitivity reactions were reported in 69% (22 of 32) of patients who received once-weekly treatment of Elaprase. Table 4 summarizes the adverse reactions that occurred in at least 9% of patients (≥3 patients) in the Elaprase 0.5 mg/kg once weekly group and with a higher incidence than in the placebo group (see Table 4).

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Additional adverse reactions that occurred in at least 9% of patients (≥3 patients) in the Elaprase 0.5 mg/kg every other week group and with a higher incidence than in the placebo group included: Rash (19%), flushing (16%), fatigue (13%), tachycardia (9%) and chills (9%).
Extension Trial: An open-label extension trial was conducted in patients who completed the placebo-controlled trial. Ninety-four (94) of the 96 patients who were enrolled in the placebo-controlled trial consented to participate in the extension trial. All 94 patients received Elaprase 0.5 mg/kg once weekly for 24 months. No new serious adverse reactions were reported. Approximately half (53%) of patients experienced hypersensitivity reactions during the 24-month extension trial. In addition to the adverse reactions listed in Table 4, common hypersensitivity reactions occurring in at least 5% of patients (≥5 patients) in the extension trial included: Rash (23%), pyrexia (9%), flushing (7%), erythema (7%), nausea (5%), dizziness (5%), vomiting (5%) and hypotension (5%).
Clinical Trial in Patients ≤7 Years: A 53-week, open-label, single-arm, safety trial of once weekly Elaprase 0.5 mg/kg treatment was conducted in patients with Hunter syndrome, ages 16 months to 4 years (n=20) and ages 5-7.5 years (n=8) at enrollment. Patients experienced similar adverse reactions as those observed in clinical trials in patients ≥5 years, with the most common adverse reactions following Elaprase treatment being hypersensitivity reactions (57%). A higher incidence of the following common hypersensitivity reactions were reported in this younger age group: Pyrexia (36%), rash (32%) and vomiting (14%). The most common serious adverse reactions occurring in at least 10% of patients (≥3 patients) included: Bronchopneumonia/pneumonia (18%), ear infection (11%) and pyrexia (11%).
Twenty-seven (27) patients had results of genotype analysis: 15 patients had complete gene deletion, large gene rearrangement, nonsense, frameshift or splice site mutations and 12 patients had missense mutations.
Safety results demonstrated that patients with complete gene deletion, large gene rearrangement, nonsense, frameshift or splice site mutations are more likely to experience hypersensitivity reactions and have serious adverse reactions following Elaprase administration, compared to patients with missense mutations. Table 5 summarizes these findings. (See Table 5.)

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Immunogenicity: Clinical Trials in Patients ≥5 Years: As with all therapeutic proteins, there is potential for immunogenicity. In clinical trials in patients ≥5 years, 63 of the 64 patients treated with Elaprase 0.5 mg/kg once weekly or placebo for 53 weeks, followed by Elaprase 0.5 mg/kg once weekly in the extension trial, had immunogenicity data available for analysis. Of the 63 patients, 32 (51%) patients tested positive for anti-idursulfase immunoglobulin G (IgG) Ab at least 1 time (see Table 5). Of the 32 Ab-positive patients, 23 (72%) tested positive for Ab at ≥3 different time points (persistent Ab). The incidence of hypersensitivity reactions was higher in patients who tested positive for Ab than those who tested negative.
Thirteen (13) of 32 (41%) Ab-positive patients also tested positive for Ab that neutralize idursulfase uptake into cells (uptake NAb) or enzymatic activity (activity NAb) at least 1 time, and 8 (25%) of Ab-positive patients had persistent NAb. There was no clear relationship between the presence of either Ab or NAb and therapeutic response.
Clinical Trial in Patients ≤7 Years: In the clinical trial in patients ≤7 years, 19 of 28 (68%) patients treated with Elaprase 0.5 mg/kg once weekly tested Ab-positive. Of the 19 Ab-positive patients, 16 (84%) tested positive for Ab at ≥3 different time points (persistent Ab). In addition, 15 of 19 (79%) Ab-positive patients tested positive for NAb, with 14 of 15 (93%) NAb-positive patients having persistent NAb.
All 15 patients with complete gene deletion, large gene rearrangement, nonsense, frameshift or splice site mutations tested positive for Ab (see Table 5). Of these 15 patients, NAbs were observed in 13 (87%) patients. The NAbs in these patients developed earlier (most reported to be positive at week 9 rather than at week 27, as reported in clinical trials in patients >5 years) and were associated with higher titers and greater in vitro neutralizing activity than in patients >5 years. The presence of Ab was associated with reduced systemic idursulfase exposure (see Pharmacology: Pharmacokinetics under Actions).
The immunogenicity data reflect the percentage of patients whose test results were positive for Ab to idursulfase in specific assays, and are highly dependent on the sensitivity and specificity of these assays. Additionally, the observed incidence of Ab positivity in an assay may be influenced by several factors, including sample handling, timing of sample collection, concomitant medication and underlying disease. For these reasons, comparison of the incidence of Ab to idursulfase with the incidence of Ab to other products may be misleading.
Post-Marketing Experience: The following adverse reactions have been identified during post approval use of Elaprase. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
In post-marketing experience, late-emergent symptoms and signs of anaphylactic reactions have occurred up to 24 hrs after initial treatment and recovery from an initial anaphylactic reaction. In addition, patients experienced repeated anaphylaxis over a 2-4 month period, up to several years after initiating Elaprase treatment (see previous texts).
A 7 year-old male patient with Hunter syndrome, who received Elaprase at twice the recommended dosage (1 mg/kg weekly) for 1.5 years, experienced 2 anaphylactic events after 4.5 years of treatment. Treatment has been withdrawn (see Overdosage).
Serious adverse reactions that resulted in death included cardiorespiratory arrest, respiratory failure, respiratory distress, cardiac failure and pneumonia.
Drug Interactions
Incompatibilities: Elaprase should not be infused with other products in the infusion tubing.
Caution For Usage
Preparation Instructions: Elaprase should be prepared and administered by a healthcare professional using aseptic techniques.
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, as illustrated on the formula as follows.

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Round-up to the next whole vial to determine the total number of whole vials needed from which to withdraw the calculated volume of Elaprase to be administered. Remove the required number of vials from the refrigerator to allow them to reach room temperature.
Before withdrawing the Elaprase solution from the vial, perform a visual inspection of each vial for particulate matter and discoloration. Elaprase is a clear to slightly opalescent, colorless solution. Do not use if the solution in the vial is discolored or particulate matter is present. Elaprase should not be shaken.
Withdraw the calculated volume of Elaprase from the appropriate number of vials.
Dilute the total calculated volume of Elaprase in sodium chloride 0.9% injection 100 mL. Once diluted into normal saline, the solution in the infusion bag should be mixed gently, but not shaken.
Elaprase is supplied in single-use vials. Remaining Elaprase left in a vial after withdrawing the patient's calculated dose should be disposed of in accordance with local requirements.
Storage
Store Elaprase vials under refrigeration at 2-8°C (36-46°F). Protect from light. Do not freeze or shake.
Elaprase contains no preservatives. The diluted solution should be used immediately. If immediate use is not possible, the diluted solution can be stored refrigerated at 2-8°C (36-46°F) for up to 24 hrs.
Other than during infusion, do not store the diluted Elaprase solution at room temperature.
ATC Classification
A16AB09 - idursulfase ; Belongs to the class of enzymes. Used in the treatment of alimentary tract and metabolism problems.
Presentation/Packing
Inj (sterile, nonpyrogenic, aqueous, clear to slightly opalescent, colorless solution for IV infusion, in single-dose vial) 2 mg/mL x 3 mL.
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