Leitlinien & Arzneimittelsicherheit

HOS-094410 · has-adverse-reaction-information · PDF-Seite 5

Summary of the safety profile Adverse reactions that were reported for the 32 patients treated with 0.5 mg/kg idursulfase weekly in the TKT024 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 1 580 infusions. In the placebo treatment group 128 infusion-related reactions were reported in 21 out of 32 patients following administration of a total of 1 612 infusions. Since more than one infusion-related reaction may have occurred during any single infusion, the above numbers are likely to overestimate 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, and erythema), pyrexia, flushing, wheezing, dyspnoea, headache, vomiting, abdominal pain, nausea, and chest pain. The frequency of infusion-related reactions decreased over time with continued treatment. Tabulated list of adverse reactions Adverse reactions are listed in table 1 with information presented by system organ class and frequency. Frequency is given as very common (≥ 1/10), common (≥ 1/100 to < 1/10) or uncommon (≥ 1/1 000 to < 1/100). The occurrence of an adverse reaction in a single patient is defined as common in view of the number of patients treated. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Adverse reactions only reported during the post marketing period are also included in the table with a frequency “not known” (cannot be estimated from the available data). Table 1: Adverse reactions from clinical trials and post-marketing experience in patients treated with Elaprase System organ Adverse reaction (preferred term) class Very common Common Uncommon Not known Immune system disorders Anaphylactoid/ anaphylactic reaction Nervous system disorders Headache Dizziness, tremor Cardiac disorder

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HOS-094406 · has-contraindication-information · PDF-Seite 3

Severe or life-threatening hypersensitivity to the active substance or to any of the excipients listed in section 6.1, if hypersensitivity is not controllable.

HOS-094405 · has-indication-information · PDF-Seite 2

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.

HOS-094408 · has-interaction-information · PDF-Seite 4

No formal medicinal product interaction studies have been conducted with idursulfase. Based on its metabolism in cellular lysosomes, idursulfase would not be a candidate for cytochrome P450 mediated interactions.

HOS-094409 · has-pregnancy-information · PDF-Seite 4

Pregnancy There are no or limited amount of data from the use of idursulfase in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of idursulfase during pregnancy. Breast-feeding It is not known whether idursulfase is excreted in human breast milk. Available data in animals have shown excretion of idursulfase in milk (see section 5.3). A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from idursulfase therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman. Fertility No effects on male fertility were seen in reproductive studies in male rats.

HOS-094407 · has-warning-information · PDF-Seite 3

Infusion-related reactions 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 medicinal products, such as antihistamines, antipyretics, low-dose corticosteroids (prednisone and methylprednisolone), or beta-agonist nebulisation. 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. Delaying the infusion in patients who present with an acute febrile respiratory illness should be considered. Patients using supplemental oxygen should have this treatment readily available during infusion in the event of an infusion-related reaction. Anaphylactoid/anaphylactic reactions Anaphylactoid/anaphylactic reactions, which have the potential to be life-threatening, have been observed in some patients treated with idursulfase up to several years after initiating treatment. Late emergent symptoms and signs of anaphylactoid/anaphylactic reactions have been observed as long as 24 hours after an initial reaction. If an anaphylactoid/anaphylactic 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/anaphylactic reactions may require prolonged clinical monitoring. Patients who have experienced anaphylactoid/anaphylactic reactions should be treated with caution when re-administering idursulfase, appropriately trained personnel and equipment for emergency resuscitation (including epinephrine) should be available during infusions. Severe or potentially life-threatening hypersensitivity is a contraindication to rechallenge, if hypersensitivity is not controllable (see section 4.3). 3 Patients with the complete

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