Source: European Medicines Agency (EU) Revision Year: 2020 Publisher: Genzyme Europe B.V., Paasheuvelweg 25, 1105 BP, Amsterdam, the Netherlands
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 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:
Disease management should be directed by physicians knowledgeable in the treatment of Gaucher disease.
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 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.
No dose adjustment is necessary for the paediatric population. 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 (see section 5.1).
After reconstitution and dilution, the preparation is administered by intravenous infusion. At initial infusions, Cerezyme should be administered at a rate not exceeding 0.5 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. Subsequent infusions may need to occur in a clinical setting. Dose and infusion rate should remain constant while at home, and not be changed without supervision of a health care professional.
For instructions on reconstitution and dilution of the medicinal product before administration, see section 6.6.
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 section 5.1).
No case of overdose has been reported. In patients dosages up to 240 U/kg body weight once every two weeks have been used.
Unopened vials: 3 years.
Diluted solution: From a microbiological safety point of view, the product should be used immediately. If not used immediately, in-use storage and conditions prior to use are the responsibility of the user and should not be longer than 24 hours at 2°C-8°C under protection from light.
Store in a refrigerator (2°C–8°C).
For storage conditions after dilution of the medicinal product, see section 6.3.
Cerezyme is supplied in type I borosilicate (clear) glass 20 ml vials. The closure consists of a siliconised butyl stopper with a tamper proof flip-off cap.
To provide sufficient volume to allow accurate dispensing, each vial is formulated to contain an overfill of 0.6 ml.
Pack sizes: 1, 5 or 25 vials per carton.
Not all pack sizes may be marketed.
Each vial of Cerezyme is for single use only.
The powder for concentrate for solution for infusion has to be reconstituted with water for injections, diluted with 0.9% sodium chloride intravenous solution and then administered by intravenous infusion.
Determine the number of vials to be reconstituted based on the individual patient’s dosage regimen and remove the vials from the refrigerator.
Occasionally, small dosage adjustments may be made to avoid discarding partially used vials. Dosages may be rounded to the nearest full vial, as long as the monthly administered dosage remains substantially unaltered.
Use Aseptic Technique
Reconstitute each vial with 10.2 ml water for injections; avoid forceful impact of water for injections on the powder and, by mixing gently, avoid foaming of the solution. The reconstituted volume is 10.6 ml. The pH of the reconstituted solution is approximately 6.1.
After reconstitution it is a clear, colourless liquid, free from foreign matter. The reconstituted solution must be further diluted. Before further dilution, visually inspect the reconstituted solution in each vial for foreign particles and discoloration. Do not use vials exhibiting foreign particles or discoloration. After reconstitution, promptly dilute vials and do not store for subsequent use.
The reconstituted solution contains 40 units imiglucerase per ml. The reconstituted volume allows accurate withdrawal of 10.0 ml (equal to 400 units) from each vial. Withdraw 10.0 ml reconstituted solution from each vial and combine the withdrawn volumes. Then dilute the combined volumes with 0.9% sodium chloride intravenous solution to a total volume of 100 to 200 ml. Mix the infusion solution gently.
It is recommended to administer the diluted solution through an in-line low protein-binding 0.2 μm filter to remove any protein particles. This will not lead to any loss of imiglucerase activity. It is recommended that the diluted solution be administered within 3 hours. The product diluted in 0.9% sodium chloride intravenous solution will retain chemical stability if stored up to 24 hours at 2°C and 8°C under protection from light; but microbiological safety will depend on the reconstitution and dilution having been performed aseptically.
Cerezyme contains no preservatives. Any unused product or waste material should be disposed of in accordance with local requirements.
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