Vimizim

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

Home administration under the supervision of an appropriately trained healthcare professional may be considered for patients who are tolerating their infusions well. Posology The recommended dose of elosulfase alfa is 2 mg/kg of body weight administered once a week.

The total volume of the infusion should be delivered over approximately 4 hours (see Table 1). 4). 3 Special populations Elderly patients (≥ 65 years old) The safety and efficacy of Vimizim in patients older than 65 years has not been established, and no alternative treatment regimen can be recommended in these patients.

It is not known whether elderly patients respond differently from younger patients. Paediatric population The posology in the paediatric population is the same as in adults. 1. Method of administration For intravenous infusion only. Patients weighing less than 25 kg should receive a total volume of 100 ml.

When diluted in 100 ml, the initial infusion rate should be 3 ml/hr. The infusion rate may be increased as tolerated, every 15 minutes as follows: first increase the rate to 6 ml/hr, then increase the rate every 15 minutes by 6 ml/hr increments until a maximum rate of 36 ml/hr is reached.

Patients weighing 25 kg or more should receive a total volume of 250 ml. When diluted in 250 ml, the initial infusion rate should be 6 ml/hr. The infusion rate may be increased as tolerated, every 15 minutes as follows: first increase the rate to 12 ml/hr, then increase the rate every 15 minutes by 12 ml/hr increments until a maximum rate of 72 ml/hr is reached.

Table 1:

Recommended infusion volumes and rates* Patient weight (kg) Total infusion volume (ml) Step 1 Initial infusion rate 0-15 minutes (ml/hr) Step 2 15-30 minutes (ml/hr) Step 3 30-45 minutes (ml/hr) Step 4 45-60 minutes (ml/hr) Step 5 60-75 minutes (ml/hr) Step 6 75-90 minutes (ml/hr) Step 7 90+ minutes (ml/hr) < 25 100 3 6 12 18 24 30 36 ≥ 25 250 6 12 24 36 48 60 72 * Infusion rate may be increased as tolerated by patient.

Summary of the safety profile The assessment of adverse reactions is based on the exposure of 176 patients with MPS IVA, ages 5 to 57 years old to 2 mg/kg elosulfase alfa once a week (n=58), 2 mg/kg elosulfase alfa once every other week (n=59), or placebo (n=59) in a randomised, double-blind, placebo-controlled study.

The majority of adverse reactions in clinical studies were IRs, which are defined as reactions occurring after initiation of infusion until the end of the day following the infusion. Serious IRs were observed in clinical studies and included anaphylaxis, hypersensitivity and vomiting.

The most common symptoms of IRs (occurring in ≥ 10% of patients treated with Vimizim and ≥ 5% more when compared to placebo) were headache, nausea, vomiting, pyrexia, chills and abdominal pain. IRs were generally mild or moderate, and the frequency was higher during the first 12 weeks of treatment and tended to occur less frequently with time.

Tabulated list of adverse reactions The data in Table 2 below describes adverse reactions from clinical studies in patients treated with Vimizim. 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), very rare (< 1/10,000) and not known (cannot be estimated from available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 2:

Adverse reactions in patients treated with Vimizim MedDRA System organ class MedDRA Preferred term Frequency Immune system disorders Anaphylaxis Uncommon Hypersensitivity Common Nervous system disorders Headache Very common Dizziness Very common Respiratory, thoracic, and mediastinal disorders Dyspnoea Very common Gastrointestinal disorders Diarrhoea, vomiting, oropharyngeal pain, upper abdominal pain, abdominal pain, nausea Very common Musculoskeletal and connective Myalgia Common 6 tissue disorders Chills Very common General disorders and administration site conditions Pyrexia Very common Description of selected adverse reactions Immunogenicity All patients developed antibodies to elosulfase alfa in clinical studies.

Anaphylaxis and severe allergic reactions Anaphylaxis and severe allergic reactions have been reported in clinical studies. Therefore, appropriate medical support must be readily available when elosulfase alfa is administered. If these reactions occur, immediately stop the infusion and initiate appropriate medical treatment.

The current medical standards for emergency treatment are to be followed. For patients who have experienced allergic reactions during infusion, caution should be exercised upon re-administration. 4 Infusion reactions Infusion reactions (IRs) were the most commonly observed adverse reactions in clinical studies.

IRs may include allergic reactions. 2). Management of IRs should be based on the severity of the reaction and include slowing or temporary interruption of the infusion and/or administration of additional antihistamines, antipyretics, and/or corticosteroids.

If severe IRs occur, immediately stop the infusion and initiate appropriate treatment. Re-administration after a severe reaction should be carried out with caution and close monitoring by the treating physician. Spinal/Cervical cord compression In clinical studies, spinal/cervical cord compression (SCC) was observed both in patients receiving Vimizim and patients receiving placebo.

Patients should be monitored for signs and symptoms of SCC (including back pain, paralysis of limbs below the level of compression, urinary and faecal incontinence) and given appropriate clinical care. 6). Sorbitol (E 420) This medicinal product contains 100 mg sorbitol in each vial which is equivalent to 40 mg/kg.

Patients with hereditary fructose intolerance (HFI) must not be given this medicinal product unless strictly necessary. Babies and young children (below 2 years of age) may not yet be diagnosed with hereditary fructose intolerance (HFI).

Medicinal products containing sorbitol/fructose given intravenously may be life- threatening. The treatment benefit to the child compared to the associated risks must be fully evaluated prior to treatment. A detailed history with regard to HFI symptoms has to be taken for each patient prior to being given this medicinal product.

4).