Replagal

HOS-093110 · has-adverse-reaction-information · PDF-Seite 5

Summary of safety profile The most commonly reported adverse reactions were infusion associated reactions, which occurred in 13.7% of adult patients treated with Replagal in clinical trials. Most undesirable effects were mild to moderate in severity. Tabulated list of adverse reactions Table 1 lists adverse reactions reported for the 344 patients treated with Replagal in clinical trials, including 21 patients with history of end stage renal disease, 30 paediatric patients (≤ 18 years of age) and 98 female patients, and from post-marketing spontaneous reports. Information is presented by system organ class and frequency (very common ≥ 1/10; common ≥ 1/100 to < 1/10; uncommon ≥ 1/1 000 to < 1/100). The adverse reactions categorized as incidence “not known (cannot be estimated from the available data)” are derived from post-marketing spontaneous reports. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. The occurrence of an event in a single patient is defined as uncommon in view of the number of patients treated. A single patient could be affected by several adverse reactions. The following adverse reactions have been identified for agalsidase alfa: Table 1 System organ class Adverse reaction Very common Common Uncommon Not known Metabolism and peripheral nutrition disorders oedema 5  Table 1 System organ class Adverse reaction Very common Common Uncommon Not known Nervous system headache, dysgeusia, parosmia disorders dizziness, hypersomnia neuralgia, tremor, hypoesthesia, paraesthesia Eye disorders lacrimation corneal reflex increased decreased Ear and labyrinth tinnitus tinnitus disorders aggravated Cardiac disorders palpitations tachycardia, tachyarrhythmia myocardial atrial fibrillation ischaemia,

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HOS-093106 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-093105 · has-indication-information · PDF-Seite 2

Replagal is indicated for long-term enzyme replacement therapy in patients with a confirmed diagnosis of Fabry Disease (α-galactosidase A deficiency).

HOS-093108 · has-interaction-information · PDF-Seite 4

Replagal should not be co-administered with chloroquine, amiodarone, benoquin or gentamicin since these substances have the potential to inhibit intra-cellular α-galactosidase activity. As α-galactosidase A is itself an enzyme, it would be an unlikely candidate for cytochrome P450 mediated drug-drug interactions. In clinical studies, neuropathic pain medicinal products (such as 4 carbamazepine, phenytoin, and gabapentin) were administered concurrently to most patients without any evidence of interaction.

HOS-093109 · has-pregnancy-information · PDF-Seite 5

Pregnancy There is very limited data on pregnancies exposed to Replagal. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy or embryonic/foetal development when exposed during organogenesis (see section 5.3). Caution should be exercised when prescribing to pregnant women. Breast-feeding It is not known whether Replagal is excreted in human milk. Caution should be exercised when prescribing to breast-feeding women. Fertility No effects on male fertility were seen in reproductive studies in male rats.

HOS-093107 · has-warning-information · PDF-Seite 3

Traceability In order to improve the traceability of biological medicinal products, the name and batch number of the administered product should be clearly recorded. Idiosyncratic infusion related reactions 13.7% of adult patients treated with Replagal in clinical trials have experienced idiosyncratic infusion related reactions. Four of 17 (23.5%) paediatric patients ≥ 7 years of age enrolled in clinical trials experienced at least one infusion reaction over a period of 4.5 years of treatment (mean duration of approx. 4 years). Three of 8 (37.5%) paediatric patients < 7 years of age experienced at least one infusion related reaction over a mean observation time of 4.2 years. The most common symptoms have been rigors, headache, nausea, pyrexia, flushing and fatigue. Serious infusion reactions have been reported uncommonly; symptoms reported include pyrexia, rigors, tachycardia, urticaria, nausea/vomiting, angioneurotic oedema with throat tightness, stridor, and swollen tongue. Other infusion-related symptoms may include dizziness and hyperhidrosis. A review of cardiac events 3 showed that infusion reactions may be associated with hemodynamic stress triggering cardiac events in patients with pre-existing cardiac manifestations of Fabry disease. The onset of infusion related reactions has generally occurred within the first 2-4 months after initiation of treatment with Replagal although later onset (after 1 year) has been reported as well. These effects have decreased with time. If mild or moderate acute infusion reactions occur, medical attention must be sought immediately, and appropriate actions instituted. The infusion can be temporarily interrupted (5 to 10 minutes) until symptoms subside and the infusion may then be restarted. Mild and transient effects may not require medical treatment or discontinuation of the infusion. In addition, oral or intravenous pre-treatment with antihistamines and/or corticosteroids, from 1 to 24 hours prior to infusion may prevent subsequent reactions in those cases where symptomatic treatment was required. Hypersensitivity reactions Hypersensitivity reactions have been reported. If severe hypersensitivity or anaphylactic reactions occur, the administration of Replagal should be discontinued immediately and appropriate treatment initiated. The current medical standards for emergency treatment are to be observed. Antibodies to the protein As with all protein pharma

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