Cerezyme

Disease management should be directed by physicians knowledgeable in the treatment of Gaucher disease. Posology Due to the heterogeneity and the multi-systemic nature of Gaucher disease, dosage should be individualised for each patient based on a comprehensive evaluation of all clinical manifestations of 3 the disease.

Once individual patient response for all relevant clinical manifestations is well- established, dosages and frequency of administration may be adjusted with the goal to either maintain already reached optimal parameters for all clinical manifestations or further improve those clinical parameters which have not yet been normalised.

A range of dosage regimens has proven effective towards some or all of the non-neurological manifestations of the disease. Initial doses of 60 U/kg of body weight once every 2 weeks have shown improvement in haematological and visceral parameters within 6 months of therapy and continued use has either stopped progression of or improved bone disease.

Administration of doses as low as 15 U/kg of body weight once every 2 weeks has been shown to improve haematological parameters and organomegaly, but not bone parameters. The usual frequency of infusion is once every 2 weeks; this is the frequency of infusion for which the most data are available.

Paediatric population No dose adjustment is necessary for the paediatric population. 1). Method of administration After reconstitution and dilution, the preparation is administered by intravenous infusion. 5 unit per kg body weight per minute.

At subsequent administrations, infusion rate may be increased but should not exceed 1 unit per kg body weight per minute. Infusion rate increases should occur under supervision of a health care professional. Infusion of Cerezyme at home may be considered for patients who are tolerating their infusions well for several months.

Decision to have patient move to home infusion should be made after evaluation and recommendation by the treating physician. Infusion of Cerezyme by the patient or caregiver at home requires training by a health care professional in a clinical setting.

The patient or caregiver will be instructed in infusion technique and the keeping of a treatment diary. Patients experiencing adverse events during the infusion need to immediately stop the infusion process and seek the attention of a healthcare professional.

Tabulated list of adverse reactions Adverse reactions are listed by system organ class and frequency (common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100) and rare (≥1/10,000 to <1/1,000)) in the table below. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

6 MedDRA System Organ Class Common Uncommon Rare Not known Nervous system disorders Dizziness, headache, paraesthesia Cardiac disorders Tachycardia, cyanosis Vascular disorders Flushing, hypotension Transient hypertension Respiratory, thoracic and mediastinal disorders Dyspnoea, coughing Gastrointestinal disorders Vomiting, nausea, abdominal cramping, diarrhoea Immune system disorders Hypersensitivity reactions Anaphylactoid reactions Skin and subcutaneous tissue disorders Urticaria, angioedema, pruritus, rash Musculoskeletal and connective tissue disorders Arthralgia, backache General disorders and administration site conditions Infusion site discomfort, infusion site burning, infusion site swelling, injection site sterile abscess, chest discomfort, fever, rigors, fatigue Description of selected adverse reactions Hypersensitivity (including anaphylaxis) Symptoms suggestive of hypersensitivity have been noted, overall, in approximately 3% of the patients.

4). 4). 7 Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Hypersensitivity Current data using a screening ELISA followed by a confirmatory radioimmunoprecipitation assay, suggest that, during the first year of therapy, IgG antibodies to imiglucerase are formed in approximately 15% of the treated patients.

It appears that patients who will develop IgG antibody are most likely to do so within 6 months of treatment and will rarely develop antibodies to Cerezyme after 12 months of therapy. It is suggested that patients suspected of a decreased response to the treatment be monitored periodically for IgG antibody formation to imiglucerase.

8). If a patient experiences a reaction suggestive of hypersensitivity, subsequent testing for imiglucerase antibodies is advised. As with any intravenous protein product, severe allergic-type hypersensitivity reactions are possible, but occur uncommonly.

If these reactions occur, immediate discontinuation of the Cerezyme infusion is recommended and appropriate medical treatment should be initiated. The current medical standards for emergency treatment are to be observed. Patients who have developed antibodies or symptoms of hypersensitivity to Ceredase (alglucerase) should be treated with caution when administering Cerezyme (imiglucerase).

8). Careful consideration should be given to the patient’s clinical status prior to administration of Cerezyme. Antihistamines, antipyretics, and/or corticosteroids can be given to prevent or reduce IARs. However, IARs may still occur in patients after receiving pre-treatment.

If mild or moderate IARs occur regardless of pre-treatment, decreasing the infusion rate or temporarily stopping the infusion may ameliorate the symptoms. If severe IARs occur, immediate discontinuation of the administration of Cerezyme should be considered and appropriate medical treatment should be initiated.

8). Sodium This medicinal product contains 41 mg sodium per vial, equivalent to 2% of the WHO recommended maximum daily intake of 2 g sodium for an adult. 6). To be taken into consideration by patients on a controlled sodium diet. 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.

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