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Drug Details

ELAPRASE Solution for Infusion

• Drug Class Description
  Alimentary tract and metabolism products – enzymes
• Generic Name
  Lidursulfase
• Presentation
  Concentrate for solution for infusion. A clear to slightly opalescent, colourless solution. Idursulfase is produced by recombinant DNA technology in a continuous human cell line.
• Description
  Each vial of 3 ml contains 6 mg of idursulfase. Each ml contains 2 mg of idursulfase. Idursulfase is produced by recombinant DNA technology in a continuous human cell line
• Indications
  Elaprase is indicated for the long-term treatment of patients with Hunter syndrome (Mucopolysaccharidosis II, MPS II). Heterozygous females were not studied in the clinical trials. Heterozygous females were not studied in the clinical trials.
• Adult Dosage
  

  Elaprase treatment should be supervised by a physician or other healthcare professional experienced in the management of patients with MPS II disease or other inherited metabolic disorders.

  Elaprase is administered at a dose of 0.5 mg/kg body weight every week by intravenous infusion over a 3 hour period, which may be gradually reduced to 1 hour if no infusion-associated reactions are observed.

  Patients with renal or hepatic impairment

  There is no clinical experience in patients with renal or hepatic insufficiency.

  Elderly patients

  There is no clinical experience in patients over 65 years of age.

  Paediatric patients

  The dose for children and adolescents is 0.5 mg/kg body weight weekly.

  For preparation and administration instructions see section 6.6.

  There is no clinical experience in children under the age of 5.

• Child Dosage
  Paediatric patients The dose for children and adolescents is 0.5 mg/kg body weight weekly. There is no clinical experience in children under the age of 5.
• Elderly Dosage
  Elderly patients There is no clinical experience in patients over 65 years of age.
• Contra Indications
  

  Hypersensitivity to the active substance or to any of the excipients.

• Special Precautions
  

  Patients treated with idursulfase may develop infusion-related reactions (see section 4.8). During clinical trials, the most common infusion-related reactions included cutaneous reactions (rash, pruritus, urticaria), pyrexia, headache, hypertension, and flushing. Infusion-related reactions were treated or ameliorated by slowing the infusion rate, interrupting the infusion, or by administration of medicines, such as antihistamines, antipyretics, low-dose corticosteroids (prednisone and methylprednisolone), or beta-agonist nebulization. No patient discontinued treatment due to an infusion reaction during clinical studies.

  Special care should be taken when administering an infusion in patients with severe underlying airway disease. These patients should be closely monitored and infused in an appropriate clinical setting. Caution must be exercised in the management and treatment of such patients by limitation or careful monitoring of antihistamine and other sedative medicinal product use. Institution of positive-airway pressure may be necessary in some cases.

  Consider delaying the infusion in patients who present with an acute febrile respiratory illness. Patients using supplemental oxygen should have this treatment readily available during infusion in the event of an infusion-related reaction.

  Patients who develop IgM or IgG antibodies are at a higher risk of infusion reactions and other adverse reactions, however, IgE antibodies have not been observed.

  Anaphylactoid reactions, which have the potential to be life threatening, have been observed in some patients treated with Elaprase, as with any intravenous protein product. Late emergent symptoms and signs of anaphylactoid reactions have been observed as long as 24 hours after an initial reaction. If an anaphylactoid reaction occurs the infusion should be immediately suspended and appropriate treatment and observation initiated. The current medical standards for emergency treatment are to be observed. Patients experiencing severe or refractory anaphylactoid reactions may require prolonged clinical monitoring. Patients who have experienced anaphylactoid reactions should be treated with caution when re-administering Elaprase.

• Interactions
  

  No formal drug interaction studies have been conducted with Elaprase.

  Based on its metabolism in cellular lysosomes, idursulfase would not be a candidate for cytochrome P450 mediated interactions.

• Adverse Drug Reactions
  

  Adverse drug reactions that were reported for the 32 patients treated with 0.5 mg/kg Elaprase weekly in the Phase II/III 52-week placebo-controlled study were almost all mild to moderate in severity. The most common were infusion-related reactions, 202 of which were reported in 22 out of 32 patients following administration of a total of 1580 infusions. In the placebo treatment group 128 infusion-related reactions were reported in 21 out of 32 patients following administration of a total of 1612 infusions. Since more than one infusion-related reaction may have occurred during any single infusion, the above numbers are likely to over estimate the true incidence of infusion reactions. Related reactions in the placebo group were similar in nature and severity to those in the treated group. The most common of these infusion-related reactions included cutaneous reactions (rash, pruritus, urticaria), pyrexia, headache, and hypertension. The frequency of infusion-related reactions decreased over time with continued treatment.

  Adverse drug reactions are listed in the table below with information presented by system organ class and frequency. Frequency is given as very common (>1/10) or common (>1/100, <1/10). The occurrence of an event in a single patient is defined as common in view of the number of patients treated. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

  Adverse drug reactions were defined as treatment-emergent events with suspected causality and excluded non-serious events that were reported only once in a single patient; treatment emergent events with an excess incidence of at least 9% compared with placebo were also considered as adverse drug reactions.

  System Organ Class	Adverse Drug Reaction (Preferred Term)
  Nervous system disorders
  Very common:	headache
  Common:	dizziness, tremor
  Eye disorders
  Common:	lacrimation increased
  Cardiac disorders
  Common:	arrhythmia*, cyanosis
  Vascular disorders
  Very common:	hypertension
  Common:	hypotension, flushing
  Respiratory, thoracic and mediastinal disorders
  Common:	bronchospasm, pulmonary embolism*, cough, wheezing, tachypnoea, dyspnoea
  Gastrointestinal disorders
  Very common	dyspepsia
  Common:	abdominal pain, nausea, diarrhoea, swollen tongue
  Skin and subcutaneous tissue disorders
  Very common:	urticaria, rash, pruritus
  Common:	face oedema, erythema, eczema
  Musculoskeletal and connective tissue disorders
  Very common:	chest pain
  Common:	arthralgia
  General disorders and administration site conditions
  Very common:	pyrexia, infusion site swelling
  Common:	oedema peripheral

  * see serious adverse reactions below

  Across studies, serious adverse reactions were reported in a total of 5 patients who received 0.5 mg/kg weekly or every other week. Four patients experienced a hypoxic episode during one or several infusions, which necessitated oxygen therapy in 3 patients with severe underlying obstructive airway disease (2 with a pre-existing tracheostomy). The most severe episode, which was associated with a short seizure, occurred in a patient who received his infusion while he had a febrile respiratory exacerbation. In the fourth patient, who had less severe underlying disease, spontaneous resolution occurred shortly after the infusion was interrupted. These events did not recur with subsequent infusions using a slower infusion rate and administration of pre-infusion medicinal products, usually low-dose steroids, antihistamine, and beta-agonist nebulization. The fifth patient, who had pre-existing cardiopathy, was diagnosed with ventricular premature complexes and pulmonary embolism during the study.

  There have been post-marketing reports of anaphylactoid reactions.

  Across all studies, 53/108 patients (49%) developed anti-idursulfase IgG antibodies at some point. Six of the IgG positive patients also tested positive for IgM antibodies, and 1 patient tested positive for IgA antibodies. No patient developed IgE antibodies during any study. The overall neutralizing antibody rate was 11/108 patients (10%). In the 52-week study, rates of seropositivity peaked by Weeks 18 to 27 and steadily declined thereafter for the remainder of this study.

  In general, patients who tested positive for IgG antibodies were more likely to have infusion-related events than those who did not test positive. However, overall rates of infusion-related adverse events declined over time, regardless of antibody status. The reduction of urinary GAG excretion was somewhat less in patients for whom circulating anti-idursulfase antibodies were detected.