Mepsevii

Treatment should be supervised by a healthcare professional experienced in the management of patients with MPS VII or other inherited metabolic disorders. Administration of vestronidase alfa should be carried out by an appropriately trained healthcare professional with the ability to manage medical emergencies.

Posology The recommended dose of vestronidase alfa is 4 mg/kg of body weight administered by intravenous infusion every two weeks. 4). Infusion should be avoided if the patient has an acute febrile or respiratory illness at the time.

3 Special populations Elderly The safety and efficacy of vestronidase alfa in patients older than 65 years have not been established. 1). Renal and hepatic impairment The safety and efficacy of vestronidase alfa in patients with renal or hepatic impairment have not been evaluated.

No alternative dose regimen is recommended in these patients. Paediatric population The posology in the paediatric population is the same as in adults. 1. Method of administration For intravenous use only. 6. The total diluted volume of the solution for infusion should be administered with a rate titration regimen over approximately 4 hours.

5% of the total volume will be infused, with the balance infused over the subsequent three hours. 5% of the total infusion volume is delivered into the patient’s bloodstream during the first hour of infusion. 75 mL as the lowest total volume infused during the first hour.

Do not flush the line containing vestronidase alfa to avoid a rapid bolus of infused enzyme. 9%) solution for infusion may be added through a separate line (piggyback or Y tube) to maintain sufficient intravenous flow. After the first hour, the rate can be increased to infuse the remainder of the solution for infusion over 3 hours as tolerated according to the recommended rate guidelines in Table 2.

4).

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).

6 Table 1 Adverse reactions reported in patients treated with Mepsevii MedDRA System Organ Class MedDRA Preferred Term (PT) Frequency Immune system disorders Anaphylactoid reaction Very common Nervous system disorders Febrile convulsion* Common Gastrointestinal disorders Diarrhoea Common Skin and subcutaneous tissue disorders Urticaria Rash** Pruritus Very common Very common Common General disorders and administration site conditions Infusion site extravasation*** Infusion site swelling**** Very common 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 frequency of Infusion site swelling as the event is classified as intravenous catheter issue.

Description of selected adverse reactions Febrile convulsion One patient receiving a vestronidase alfa dose of 4 mg/kg experienced a febrile convulsion during treatment at the week 66, within 3 days of diphtheria, tetanus, pertussis vaccination.

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. 4 As end organ damage progresses over time, it is more difficult for the treatment to reverse the damage or to show improvements. 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. 8). Infusion should be avoided if the patient has an acute febrile or respiratory illness at the time.

2). 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.

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 and instructed to seek immediate medical care should such signs and symptoms occur.

The risks and benefits of re-administering vestronidase alfa should be considered following a severe hypersensitivity reaction. Spinal/cervical cord compression Spinal or cervical cord compression is a known and serious complication of MPS VII.

4).