COMMISSION DECISION of 18/05/98 amending the marketing authorization for the medicinal product for human use. Only the Dutch text is authentic

Transcription

1 COMMISSION DECISION of 18/05/98 amending the marketing authorization for the medicinal product for human use "CEREZYME - imiglucerase" Only the Dutch text is authentic THE COMMISSION OF THE EUROPEAN COMMUNITIES, Having regard to the Treaty establishing the European Community, Having regard to Council Regulation (EEC) No 2309/93 of 22 July 1993 laying down Community procedures for the authorization and supervision of medicinal products for human and veterinary use and establishing a European Agency for the Evaluation of Medicinal Products, 1 Having regard to Council Directive 92/27/EEC of 31 March 1992 on the labelling of medicinal products for human use and on package leaflets, 2 and in particular Article 10(3) thereof, Having regard to the request to change the package leaflet concerning the medicinal product CEREZYME imiglucerase entered in the Community register of medicinal products under Nos: EU/1/97/053/ , submitted on 25 February 1998 pursuant to Article 10(3) of the abovementioned Council Directive, Whereas the proposed changes are not connected with the contents of the summary of characteristics of the medicinal product in question; Whereas, moreover, the package leaflet as changed continue to comply with the requirements of Directive 92/27/EEC, Whereas Decision C(97) 3539 final of 17 November 1997 authorising the placing on the market of the medicinal product CEREZYME imiglucerase should therefore be amended, 1 OJ No L 214, , p OJ L 113, , p. 8. 1

2 HAS ADOPTED THIS DECISION: Article 1 Decision C(97) 3539 final is hereby amended as follows: - Annex IIIB (package leaflet) is replaced by Annex IIIB to this Decision. Article 2 This Decision is addressed to Genzyme B.V., Gooimeer 3-30, 1411 DC Naarden, The Netherlands. Done at Brussels, 18/05/98 For the Commission Martin BANGEMANN Member of the Commission 2

3 3 B. PACKAGE LEAFLET

4 1. NAME OF THE MEDICINAL PRODUCT Cerezyme imiglucerase 2. FULL STATEMENT OF THE ACTIVE SUBSTANCE AND EXCIPIENTS The active substance in Cerezyme is imiglucerase. Each vial contains 200 units of imiglucerase. The excipients are: mannitol, sodium citrate, citric acid monohydrate and polysorbate PHARMACEUTICAL FORM AND CONTENTS Cerezyme is supplied as a powder for solution for infusion. The reconstituted solution must be further diluted. 4. PHARMACO-THERAPEUTIC GROUP (ACTIVITY) Imiglucerase is a modified form of the human enzyme ß-glucocerebrosidase produced by recombinant DNA technology. Imiglucerase is used as enzyme replacement therapy when the level of enzyme activity is lower than normal as is observed in Gaucher disease. 5. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER AND MANUFACTURING AUTHORISATION HOLDER Marketing authorisation holder Genzyme B.V., Gooimeer 3-30, 1411 DC Naarden, The Netherlands Importer and manufacturing authorisation holder responsible for batch release Genzyme Ltd., 37 Hollands Road, Haverhill, Suffolk CB9 8PU, United Kingdom 6. THERAPEUTIC INDICATIONS - WHEN SHOULD CEREZYME BE USED? Cerezyme should be used for patients diagnosed with Type I Gaucher disease, who exhibit clinically significant manifestations of the disease, resulting in one or more of the following signs or symptoms: anaemia (low number of red blood cells), bleeding tendency due to low platelet count, spleen or liver enlargement or bone disease. Therapy should be directed by physicians knowledgeable in the management of Gaucher disease. 4

5 7. INFORMATION NECESSARY BEFORE TAKING THE PRODUCT Contra-indications - When should Cerezyme not be used? There are no known contra-indications to the use of Cerezyme. 5

6 What precautions should be taken when using Cerezyme? Hypersensitivity (allergy) Some patients may develop IgG antibodies to Cerezyme (imiglucerase). These patients have a higher risk of experiencing hypersensitivity (allergic) reactions to the product. Patients exhibiting unusual reactions should report these to their physician (See also undesirable effects ). Treatment in patients who have shown hypersensitivity reactions should be approached with caution. Most patients have successfully resumed therapy after a reduction in the rate of infusion and pretreatment with antihistamines and/or corticosteroids. Use during pregnancy and breast feeding Use of Cerezyme during pregnancy and breast feeding is not recommended. Women should consult with their treating physician about the appropriate action to be taken. Interactions There are no known interactions with other medicinal products. Interactions with food are unlikely. Cerezyme should not be administered as a mixture with other medicinal products in the same infusion. 8. DOSAGE AND INSTRUCTIONS FOR PROPER USE Dosage The dosage should be individualised for each patient. Disease severity and convenience should be factors considered by your physician when selecting the most appropriate dosage and schedule. Initial doses of 60 U/kg of body weight once every 2 weeks have shown improvement in blood parameters and liver and spleen volumes 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 blood parameters and liver and spleen volumes, but not bone parameters. The usual and most convenient frequency of infusion is once every 2 weeks; this is the frequency of infusion for which the most data are available. Your physician must routinely evaluate your response to treatment and dosages should only be adjusted (up or down) based on a comprehensive evaluation of your response to all relevant clinical manifestations of the disease. Once a response for all relevant clinical manifestations is well-established and stabilised, your physician may decide to adjust your dosage for continued effective 6

7 therapy, while continuing to closely monitor response parameters and your well-being. Usual monitoring intervals range from 6 to 12 months. Instructions for use - reconstitution, dilution and administration The powder for solution for infusion has to be reconstituted with water for injections, diluted in 0.9% sodium chloride intravenous solution and then administered by intravenous infusion. Remove the appropriate number of vials from the refrigerator. The number of vials to be reconstituted is based on the individual patient's dosage regimen. Use Aseptic Technique Reconstitution Reconstitute each vial with 5.1 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 5.3 ml. The ph of the reconstituted solution is approximately 6.1. 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. Cerezyme contains no preservatives. Any unused reconstituted solution must be discarded appropriately. Dilution The reconstituted solution contains 40 units imiglucerase per ml. The reconstituted volume allows accurate withdrawal of a nominal volume of 5.0 ml (equal to 200 units) from each vial. Withdraw 5.0 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 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 between 2 C and 8 C under protection from light; but microbiological safety will depend on the reconstitution and dilution having been performed aseptically. Administration Administer by intravenous infusion over 1 to 2 hours. Alternatively, the appropriate dose of Cerezyme may be administered such that a rate not exceeding 1 unit per kg body weight per minute is infused. 7

8 9. UNDESIRABLE EFFECTS - WHAT UNDESIRABLE EFFECTS MAY CEREZYME CAUSE? Patients should always inform their doctor or pharmacist about any undesirable effect, even those not mentioned in this leaflet. Patients may experience minor adverse events which are associated with the route of administration as with any intravenous infusion, i.e. discomfort, itching, burning, swelling or abscess at the site of venipuncture. Symptoms suggestive of hypersensitivity have been noted in a limited number of patients. Onset of such symptoms has occurred during or shortly after infusions; these have included itching, flushing, urticaria/angioedema, chest discomfort, and breathlessness. Fall in blood pressure associated with hypersensitivity has also been reported in a very small number of patients. Patients should be advised to discontinue infusion of the product and immediately contact their physician if these symptoms occur. Additional undesirable effects have been reported in a limited number of patients: nausea, vomiting, abdominal cramping, diarrhoea, rash, fatigue, headache, fever and dizziness. 8

9 10. SHELF-LIFE AND STORAGE PRE-CAUTIONS How to store Cerezyme Do not use Cerezyme after the expiration date printed on the labelling after the letters EXP. Cerezyme vials should be stored at a temperature between 2 C and 8 (refrigerator). 11. DATE OF LAST REVISION March OTHER INFORMATION For information about Cerezyme, please contact the (local) representative of the Marketing Authorisation holder. Danmark: Genzyme B.V. Gooimeer DC Naarden, Holland tel Belgique/België/Luxembourg: N.V. Consultancy Guy Derkinderen S.A. Vijfstraten Keerbergen, Belgique/Belgie tel Deutschland: Genzyme GmbH Röntgenstraße Alzenau, Deutschland tel fax Ελλάδα: Jasonpharm Co. Ymittou Athens, Ελλάδα tel Italia: Genzyme Srl Via Scaglia Est Modena, Italia tel Nederland: Genzyme B.V. Gooimeer DC Naarden, Nederland tel Österreich: Genzyme B.V. Gooimeer DC Naarden, Niederlande tel Portugal: Enzifarma - Diagnostica e Farmacκutica, Lda. Taguspark - Parque de Ciκncia e Tecnologia Nϊcleo Central Oeiras, Portugal tel

10 Espaρa Genzyme S.L. Avda de la Industria, Alcobendas (Madrid), Espaρa tel France: Genzyme S.A. 6, Rue de la Grande Ourse B.P Cergy St. Christophe Cergy Pontoise Cedex, France tel Suomi: Genzyme B.V. Gooimeer DC Naarden, Alankomaat tel Sverige: Genzyme B.V. Gooimeer DC Naarden Nederlδnderna tel United Kingdom/Ireland: Genzyme Ltd. 37 Hollands Road Haverhill Suffolk CB9 8PU, United Kingdom tel