Naglazyme · 4.5 Interaction with other medicinal products and other forms of interaction · 1

HOS-094228 · has-adverse-reaction-information · PDF-Seite 5

Due to the low number of patients in clinical trials, adverse event (AE) data from all Naglazyme studies have been pooled and reviewed in a single, clinical trial safety analysis. All patients treated with NAGLAZYME (59/59) reported at least one AE. The majority (42/59; 71%) of patients experienced at least one Adverse Drug Reaction. The most common adverse reactions were pyrexia, rash, pruritus, urticaria, chills/rigors, nausea, headache, abdominal pain, vomiting and dypsnoea. Serious adverse reactions included laryngeal edema, apnoea, pyrexia, urticaria, respiratory distress, angioedema, asthma and anaphylactoid reaction. Infusion reactions, defined as adverse reactions occurring during Naglazyme infusions or until the end of the infusion day, were observed in 33 (56%) of the 59 patients treated with Naglazyme across five clinical studies. Infusion reactions began as early as Week 1 and as late as Week 146 of Naglazyme treatment, and occurred during multiple infusions though not always in consecutive weeks. Very common symptoms of these infusion reactions were pyrexia, chills/rigors, rash, urticaria and dyspnoea. Common symptoms of infusion reactions were pruritus, vomiting, abdominal pain, nausea, hypertension, headache, chest pain, erythema, cough, hypotension, angioedema, respiratory distress, tremor, conjunctivitis, malaise, bronchospasm and arthralgia. Adverse reactions are listed in Table 1 by System Organ Class. The reactions are listed following the MedDRA frequency convention. Very common adverse reactions are those with a frequency of 1/10. Common reactions have a frequency of 1/100 to <1/10. Due to the small patient population, an adverse reaction in a single patient is classified as common. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Adverse reactions reported during the Post Marketing period are included at a frequency category of “unknown”. Overall, one case of sleep apnoea was experienced from all clinical studies. 5 Table 1: Frequency of adverse drug reactions with Naglazyme MedDRA MedDRA Frequency System Organ Class Preferred Term Immune system disorders Anaphylaxis, shock Unknown Infections and infestations Pharyngitis1, gastroenteritis1 V

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HOS-094224 · has-contraindication-information · PDF-Seite 3

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

HOS-094223 · has-indication-information · PDF-Seite 2

Naglazyme is indicated for long-term enzyme replacement therapy in patients with a confirmed diagnosis of Mucopolysaccharidosis VI (MPS VI; N-acetylgalactosamine 4-sulfatase deficiency; Maroteaux-Lamy syndrome) (see section 5.1).

HOS-094226 · has-interaction-information · PDF-Seite 5

No interaction studies have been performed.

HOS-094227 · has-pregnancy-information · PDF-Seite 5

Pregnancy For Naglazyme, no clinical data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy or embryo-foetal development (see section 5.3). Naglazyme should not be used during pregnancy unless clearly necessary. Breast-feeding It is not known whether galsulfase is excreted in milk, therefore breast-feeding should be stopped during Naglazyme treatment. Fertility Reproduction studies have been performed in rats and rabbits at doses up to 3 mg/kg/day and have revealed no evidence of impaired fertility or harm to the embryo or foetus due to Naglazyme.

HOS-094225 · has-warning-information · PDF-Seite 3

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Management of compromised airways Caution must be exercised in the management and treatment of patients with compromised airways by limitation or careful monitoring of antihistamine and other sedative medicinal product use. Institution of positive–airway pressure during sleep as well as potential tracheostomy in clinically appropriate situations should also be considered. Patients who present with an acute febrile or respiratory illness may need to have their Naglazyme infusions delayed. Management of infusion-associated reactions Patients treated with Naglazyme have developed infusion-associated reactions (IARs), defined as any adverse reactions occurring during the infusion or until the end of the infusion day (see section 4.8). Based on data obtained during Naglazyme clinical trials, the majority of patients are expected to develop IgG antibodies to galsulfase within 4-8 weeks of treatment initiation. In the Naglazyme clinical trials, IARs were usually manageable by interrupting or slowing the rate of infusion and by (pre-) treating the patient with antihistamines and/or antipyretics (paracetamol), thus enabling the patient to continue treatment. As there is little experience on resumption of treatment following prolonged interruption, caution is to be used due to the theoretical increased risk of hypersensitivity reaction. 3 With administration of Naglazyme it is recommended that patients be administered pre-treatment medicinal products (antihistamines with or without antipyretics) approximately 30-60 minutes prior to the start of the infusion, to minimise the potential occurrence of IARs. In case of a mild or moderate IAR, treatment with antihistamines and paracetamol should be considered and/or a reduction in the infusion rate to half the rate at which the reaction occurred. In case of a single severe IAR, the infusion should be stopped until the symptoms are resolved and treatment with antihistamines and paracetamol should be considered. The infusion can be restarted with a reduction of the infusion rate to 50% – 25% of the rate at which the reaction occurred. In case of a recurrent moderate IAR or re-challenge after a single severe IAR, pre-treatment should be considered (antihistamines and paracetamol and/or cor

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