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

HOS-098305 · has-adverse-reaction-information · PDF-Seite 5

Summary of the safety profile The most common adverse reactions from 4 clinical trials in 23 patients treated with vestronidase alfa were rash (17.4%), urticaria (17.4%), infusion site extravasation (17.4%), anaphylactoid reaction (13%), infusion site swelling (8.7%), pruritus (8.7%) and diarrhoea (8.7%). Most adverse reactions were mild to moderate in severity. Tabulated list of adverse reactions The assessment of adverse reactions was based on the exposure of 23 patients from 4 clinical trials, aged 5 months to 25 years, who received vestronidase alfa at doses up to 4 mg/kg once every two weeks for up to 187 weeks. Nineteen patients were younger than 18 years of age. Table 1 lists the adverse reactions reported from 4 clinical trials in 23 patients treated with Mepsevii. Adverse reactions are presented by System Organ Class and frequency. Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare ( ≥ 1/10 000 to < 1/1 000), and very rare (< 1/10 000). 5 Table 1 Adverse reactions reported in patients treated with Mepsevii MedDRA System Organ Class MedDRA Preferred Frequency Term (PT) Immune system disorders Anaphylactoid reaction Very common Nervous system disorders Febrile convulsion* Common Gastrointestinal disorders Diarrhoea Common Skin and subcutaneous tissue disorders Urticaria Very common Rash** Very common Pruritus Common General disorders and administration site Infusion site Very common conditions extravasation*** Infusion site swelling**** Common *Refer to description of selected adverse reactions for details on the febrile convulsion reported in 1 of 23 trial patients. ** Rash includes grouped PTs of rash, rash papular, rash pruritic, rash maculo-papular, papule, and macule *** Infusion site extravasation includes one PT of extravasation **** One adverse reaction of Peripheral swelling is included within the

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HOS-098301 · has-contraindication-information · PDF-Seite 3

Life-threatening hypersensitivity (anaphylactic reaction) to the active substance or to any of the excipients listed in section 6.1 (see section 4.4).

HOS-098300 · has-indication-information · PDF-Seite 2

Mepsevii is indicated for the treatment of non-neurological manifestations of Mucopolysaccharidosis VII (MPS VII; Sly syndrome).

HOS-098303 · has-interaction-information · PDF-Seite 4

No interaction studies have been performed. Because it is a recombinant human protein and its enzyme action is within the lysosome, vestronidase alfa is not expected to interact with other medicinal products. 4

HOS-098304 · has-pregnancy-information · PDF-Seite 5

Pregnancy There are no data on the use of vetronidase alfa in pregnant women. Animal studies with vestronidase alfa do not indicate direct or indirect harmful effects with respect to pregnancy, embryo-foetal development, or pre- and postnatal development (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Mepsevii during pregnancy, unless the potential benefit to the mother outweighs the potential theoretical risks to the foetus. Breast-feeding There are no data from studies in breast-feeding women. It is not known whether vestronidase alfa is excreted in human milk, but systemic exposure via breast-milk is not expected. Due to lack of human data, vestronidase alfa should only be administered to a breast-feeding woman if the potential benefit of vestronidase alfa to the mother and the benefit of breast-feeding to the infant outweighs the potential theoretical risks to the infant. Fertility No human data are available on the effect of vestronidase alfa on fertility. Animal studies with vestronidase alfa do not indicate any impact on male or female fertility (see section 5.3).

HOS-098302 · 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. General The effects of treatment with vestronidase alfa should be periodically evaluated and discontinuation of treatment should be considered in cases where clear benefits (including stabilisation of disease manifestations) are not observed. Discontinuation of treatment may cause significant worsening of the patient’s clinical status. 3 As end organ damage progresses over time, it is more difficult for the treatment to reverse the damage or to show improvements. It should be considered by the treating physician that the administration of vestronidase alfa does not affect the irreversible complications (e.g. skeletal deformities). Vestronidase alfa, at the exposure observed in humans, is not expected to cross the blood-brain-barrier and therefore it is not likely to impact the neurological manifestations of the disease. Hypersensitivity reactions including anaphylaxis Serious hypersensitivity reactions, including anaphylaxis, have been reported with vestronidase alfa; therefore, appropriate medical support should be readily available when vestronidase alfa is administered (see section 4.8). Infusion should be avoided if the patient has an acute febrile or respiratory illness at the time. It is recommended that premedication with non-sedating antihistamines with or without antipyretics be administered 30-60 minutes prior to the start of the infusion (see section 4.2). It is important to administer vestronidase alfa according to the recommended infusion rate schedule (see Table 2 in section 6.6). If severe hypersensitivity reactions occur, the infusion of vestronidase alfa should be stopped immediately and appropriate treatment should be initiated. Management of hypersensitivity reactions should be based on the severity of the reaction and include temporary interruption or discontinuation of the infusion and/or administration of additional antihistamines, antipyretics, and/or corticosteroids for mild to moderate reactions. Consider rapid sodium chloride 9 mg/mL (0.9%) solution for infusion for decreased blood pressure and oxygen for hypoxia. Patients should be observed for a minimum of 60 minutes after completing the infusion of vestronidase alfa. Patients should be informed of the signs and symptoms of hypersensitivity reactions

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