Enzymes-Imiglucerase (recombinant macrophage targeted ß-glucocerebrosidase)

Imiglucerase

Cerezyme 200 U Powder for concentrate for solution for infusion

Powder for concentrate for solution for infusion. Cerezyme is a white to off-white powder.

Cerezyme (imiglucerase) is indicated for use as long-term enzyme replacement therapy in patients with a confirmed diagnosis of non-neuronopathic (Type 1) or chronic neuronopathic (Type 3) Gaucher disease and who exhibit clinically significant non-neurological manifestations of the disease. The non-neurological manifestations of Gaucher disease include one or more of the following conditions:

• anaemia after exclusion of other causes, such as iron deficiency
• thrombocytopenia
• bone disease after exclusion of other causes such as Vitamin D deficiency
• hepatomegaly or splenomegaly The non-neurological manifestations of Gaucher disease include one or more of the following conditions:
• anaemia after exclusion of other causes, such as iron deficiency
• thrombocytopenia
• bone disease after exclusion of other causes such as Vitamin D deficiency
• hepatomegaly or splenomegaly

Therapy should be directed by physicians knowledgeable in the management of Gaucher disease.

Posology for Adults, Children and Elderly

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 the clinical manifestations of the disease.

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 2.5 U/kg of body weight three times a week or 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, and for the patient, most convenient frequency of infusion is once every 2 weeks; this is the frequency of infusion for which the most data are available.

Patient responses must be routinely evaluated and dosages should only be adjusted (up or down) based on a comprehensive evaluation of patient response relating to all clinical manifestations of the disease. Once individual patient response for all relevant clinical manifestations is well-established and stabilised, dosages may be adjusted for continued effective therapy, while continuing to closely monitor response parameters and patient well-being. Usual monitoring intervals range from 6 to 12 months.

The efficacy of Cerezyme on neurological symptoms of chronic neuronopathic Gaucher patients has not been established and no special dosage regimen can be recommended for these manifestations.

After reconstitution and dilution the preparation is administered by intravenous infusion over 1 to 2 hours. Alternatively, the appropriate dose of Cerezyme may be administered at a rate not exceeding 1 unit per kg body weight per minute.

Medical or healthcare professionals are encouraged to register Gaucher patients, including those with chronic neuronopathic manifestations of the disease, in the “ICGG Gaucher Registry”.

See Adult Dosage

See Adult Dosage

Hypersensitivity to the active substance or to any of the excipients.

Hypersensitivity

Current data 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.

Patients with antibody to Cerezyme (imiglucerase) have a higher risk of hypersensitivity reactions. 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. 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).

Pulmonary hypertension

Pulmonary hypertension is a known complication of Gaucher disease. It has been observed both in patients receiving and not receiving enzyme replacement therapy. No causal relationship with enzyme replacement therapy has been established. Patients with respiratory symptoms should be evaluated for the presence of pulmonary hypertension.

Excipients

This medicinal product contains sodium and is administered in 0.9% sodium chloride intravenous solution. To be taken into consideration by patients on a controlled sodium diet.

No interaction studies have been performed.

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

Nervous system disorders
Uncommon: Dizziness, headache, paraesthesia

Cardiac disorders
Uncommon: Tachycardia, cyanosis

Vascular disorders
Uncommon: Flushing, hypotension

Respiratory, thoracic and mediastinal disorders
Common: Respiratory symptoms

Gastrointestinal disorders
Uncommon: Vomiting, nausea, abdominal cramping, diarrhoea

Skin and subcutaneous tissue disorders
Common: Urticaria/angioedema, pruritus, rash

Musculoskeletal and connective tissue disorders
Uncommon: Arthralgia

General disorders and administration site conditions
Uncommon: Infusion site discomfort, infusion site burning, infusion site swelling, injection site sterile abscess, chest discomfort, fever, rigors, fatigue

In a small number of patients undesirable effects have been reported which are related to the route of administration: discomfort, pruritus, burning, swelling or sterile abscess at the site of venipuncture. Symptoms suggestive of hypersensitivity have been noted in approximately 3% of the patients. Onset of such symptoms has occurred during or shortly after infusions; these have included pruritus, flushing, urticaria/angioedema, chest discomfort, tachycardia, cyanosis, respiratory symptoms, and paraesthesia. Hypotension associated with hypersensitivity has also been reported rarely. These symptoms generally respond to treatment with antihistamines and/or corticosteroids. Patients should be advised to discontinue infusion of the product and contact their physician if these symptoms occur.

Genzyme Therapeutics

(POM)

13 August 2009