Package leaflet: Information for the user

Fabrazyme 35 mg powder for concentrate for solution for infusion

agalsidase beta

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.

• If you have any further questions, ask your doctor or pharmacist.

• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

  
  

  What is in this leaflet

  1. What Fabrazyme is and what it is used for

  2. What you need to know before you use Fabrazyme

  3. How to use Fabrazyme

  4. Possible side effects

  5. How to store Fabrazyme

  6. Contents of the pack and other information

  
  

  1. What Fabrazyme is and what it is used for

     
     

     Fabrazyme contains the active substance agalsidase beta and is used as enzyme replacement therapy in Fabry disease, where the level of -galactosidase enzyme activity is absent or lower than normal. If you suffer from Fabry disease a fat substance, called globotriaosylceramide (GL-3), is not removed from the cells of your body and starts to accumulate in the walls of the blood vessels of your organs.

     
     

     Fabrazyme is indicated for use as long-term enzyme replacement therapy in patients with a confirmed diagnosis of Fabry disease.

     
     

     Fabrazyme is indicated in adults, children and adolescents aged 8 years and older.

     
     

  2. What you need to know before you use Fabrazyme Do not use Fabrazyme

• if you are allergic to agalsidase beta or any of the other ingredients of this medicine (listed in section 6).

  
  

  Warnings and precautions

  Talk to your doctor or pharmacist before using Fabrazyme.

  
  

  If you are treated with Fabrazyme, you may develop infusion associated reactions. An infusion- associated reaction is any side effect occurring during the infusion or until the end of the infusion day (see section 4). If you experience a reaction like this, you should tell your doctor immediately. You may need to be given additional medicines to prevent such reactions from occurring.

  
  

  Children and adolescents

  No clinical studies have been performed in children 0-4 years old. The risks and benefits of Fabrazyme in children aged 5 to 7 years have not yet been established and therefore no dose can be recommended for this age group.

  Other medicines and Fabrazyme

  Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

  Tell your doctor if you use any medicines containing chloroquine, amiodarone, benoquin or gentamicin. There is a theoretical risk of decreased agalsidase beta activity.

  
  

  Pregnancy, breast-feeding and fertility

  Use of Fabrazyme during pregnancy is not recommended. There is no experience with the use of Fabrazyme in pregnant women. Fabrazyme may get into breast milk. Use of Fabrazyme during breast- feeding is not recommended. Studies have not been performed to examine the effects of Fabrazyme on fertility.

  
  

  If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

  
  

  Driving and using machines

  Do not drive or use machines if you experience dizziness, sleepiness, vertigo or fainting during or shortly after administration of Fabrazyme (see section 4). Talk to your doctor first.

  
  

  Fabrazyme contains sodium

  This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially ‘sodium- free’.

  
  

  1. How to use Fabrazyme

     
     

     Fabrazyme is given through a drip into a vein (by intravenous infusion). It is supplied as a powder which will be mixed with sterile water before it is given (see information for Health Care Professionals at the end of this leaflet).

     Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not sure.

     
     

     Fabrazyme is only used under the supervision of a doctor who is knowledgeable in the treatment of Fabry disease. Your doctor may advise that you can be treated at home provided you meet certain criteria. Please contact your doctor if you would like to be treated at home.

     
     

     The recommended dose of Fabrazyme for adults is 1 mg/kg body weight, once every 2 weeks. No changes in dose are necessary for patients with kidney disease.

     
     

     Use in children and adolescents

     The recommended dose of Fabrazyme for children and adolescents 8 – 16 years is 1 mg/kg body weight, once every 2 weeks. No changes in dose are necessary for patients with kidney disease.

     
     

     If you use more Fabrazyme than you should

     Doses up to 3 mg/kg body weight have shown to be safe.

     
     

     If you forget to use Fabrazyme

     If you have missed an infusion of Fabrazyme, please contact your doctor.

     
     

     If you have any further questions on the use of this medicine, ask your doctor.

     
     

  2. Possible side effects

     
     

     Like all medicines, this medicine can cause side effects, although not everybody gets them.

     
     

     In clinical studies side effects were mainly seen while patients were being given the medicine or shortly after (“infusion related reactions”). Severe life-threatening allergic reactions (“anaphylactoid

     reactions”) have been reported in some patients. If you experience any serious side effect, you should

     contact your doctor immediately.

     
     

     Very common symptoms (may affect more than 1 in 10 people) include chills, fever, feeling cold, nausea, vomiting, headache and abnormal feelings in the skin such as burning or tingling. Your doctor may decide to lower the infusion rate or give you additional medicines to prevent such reactions from occurring.

     
     

     List of other side effects:

     
     

     Common (may affect up to 1 in 10 people):

     • chest pain • sleepiness • fatigue

     • difficulty in breathing • increased heart beat • flushing

     • pallor • abdominal pain • pain

     • itching • back pain • throat tightness

     • abnormal tear secretion • rash • dizziness

     • feeling weak • low heart rate • palpitations

     • tinnitus • lethargy • decreased sensitivity to pain

     • nasal congestion • syncope • burning sensation

     • diarrhoea • cough • wheezing

     • redness • abdominal discomfort • urticaria

     • muscle pain • swelling face • pain at the extremities

     • increased blood pressure • joint pain • nasopharyngitis

     • sudden swelling of the face or throat

     • decreased blood pressure • hot flush

     • oedema in extremities • chest discomfort • feeling hot

     • vertigo • face oedema • hyperthermia

     • stomach discomfort • exacerbated difficulty in

       breathing

     • decreased mouth sensitivity

       tremor

       • itching eyes

       • low heart rate due to conduction disturbances

       • red eyes

       • ear swelling

       • increased sensitivity to pain

       • ear pain

       • bronchospasm

       • upper respiratory tract congestion

       • throat pain

       • runny nose

       • red rash

       • fast breathing

       • heart burn

       • (mottled purplish) skin discolouration

       • itchy rash

       • skin discomfort

       • coldness of the extremities

       • feeling hot and cold

       • musculoskeletal pain

       • injection site blood clotting

       • difficulty swallowing

       • rhinitis

       • skin discolouration

       • infusion site pain

       • influenza-like illness

       • oedema

       • infusion site reaction

       • malaise

       muscle spasms • muscle tightness • musculoskeletal stiffness Uncommon (may affect up to 1 in 100 people):

       
       

       Not known (frequency cannot be estimated from the available data):

       lower blood oxygen levels • serious inflammation of the

       vessels

       
       

       In some patients initially treated at the recommended dose, and whose dose was later reduced for an extended period, some symptoms of Fabry disease were reported more frequently.

       
       

       Reporting of side effects

       If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system

       

       listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

       
       

       How to store Fabrazyme

       
       

       Keep this medicine out of the sight and reach of children.

       
       

       Do not use this medicine after the expiry date which is stated on the label after ‘EXP’. The expiry date refers to the last day of that month.

       
       

       Unopened vials

       Store in a refrigerator (2C – 8C).

       
       

       Reconstituted and diluted solutions

       The reconstituted solution cannot be stored and should be promptly diluted. The diluted solution can be held for up to 24 hours at 2C – 8C.

       
       

       Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

       
       

       Contents of the pack and other information What Fabrazyme contains

       The active substance is agalsidase beta, one vial contains 35 mg. After reconstitution each vial contains 5 mg of agalsidase beta per ml.

       The other ingredients are:

       • Mannitol (E421)

       • Sodium dihydrogen phosphate monohydrate (E339)

       • Disodium phosphate heptahydrate (E339).

       
       

       What Fabrazyme looks like and contents of the pack

       Fabrazyme is supplied as a white to off-white powder. After reconstitution it is a clear, colourless liquid, free from foreign matter. The reconstituted solution must be further diluted.

       Package sizes: 1, 5 and 10 vials per carton. Not all pack sizes may be marketed.

       Marketing Authorisation Holder and Manufacturer Marketing authorisation holder

       Genzyme Europe B.V., Paasheuvelweg 25, 1105 BP Amsterdam, The Netherlands

       
       

       Manufacturer

       Genzyme Ireland Limited, IDA Industrial Park, Old Kilmeaden Road, Waterford, Ireland

       For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

       
       

       België/Belgique/Belgien/ Luxembourg/Luxemburg Sanofi Belgium

       Tél/Tel: + 32 2 710 54 00

       Lietuva

       Swixx Biopharma UAB Tel: +370 5 236 91 40

       
       

       България

       Swixx Biopharma EOOD Тел.: +359 (0)2 4942 480

       Magyarország SANOFI-AVENTIS Zrt. Tel: +36 1 505 0050

       
       

       Česká republika sanofi-aventis, s.r.o. Tel: +420 233 086 111

       Malta

       Sanofi S.r.l.

       Tel: +39 02 39394275

       
       

       Danmark

       Sanofi A/S

       Tlf: +45 45 16 70 00

       Nederland

       Genzyme Europe B.V. Tel: +31 20 245 4000

       
       

       Deutschland

       Sanofi-Aventis Deutschland GmbH Tel.: 0800 04 36 996

       Tel. aus dem Ausland: +49 69 305 70 13

       Norge

       sanofi-aventis Norge AS Tlf: + 47 67 10 71 00

       
       

       Eesti

       Swixx Biopharma OÜ Tel: +372 640 10 30

       Österreich

       sanofi-aventis GmbH Tel: + 43 1 80 185 - 0

       
       

       Ελλάδα

       sanofi-aventis AEBE Τηλ: +30 210 900 1600

       Polska

       sanofi-aventis Sp. z o.o. Tel.: +48 22 280 00 00

       
       

       España

       sanofi-aventis, S.A. Tel: +34 93 485 94 00

       Portugal

       Sanofi – Produtos Farmacêuticos, Lda. Tel: +351 21 35 89 400

       
       

       France

       sanofi-aventis France Tél: 0 800 222 555

       Appel depuis l’étranger: +33 1 57 63 23 23

       România

       Sanofi Romania SRL Tel: +40 (0) 21 317 31 36

       
       

       Hrvatska

       Swixx Biopharma d.o.o. Tel: +385 1 2078 500

       Slovenija

       Swixx Biopharma d.o.o. Tel: +386 1 235 51 00

       
       

       Ireland

       sanofi-aventis Ireland Ltd. T/A SANOFI Tel: +353 (0) 1 403 56 00

       Slovenská republika Swixx Biopharma s.r.o. Tel: +421 2 208 33 600

       
       

       Ísland

       Vistor hf.

       Sími: +354 535 7000

       Suomi/Finland

       Sanofi Oy

       Puh/Tel: + 358 201 200 300

       
       

       Italia

       Sanofi S.r.l. Tel: 800536389

       Sverige

       Sanofi AB

       Tel: +46 (0)8 634 50 00

       Κύπρος

       C.A. Papaellinas Ltd. Τηλ: +357 22 741741

       United Kingdom (Northern Ireland) sanofi-aventis Ireland Ltd. T/A SANOFI Tel: +44 (0) 800 035 2525

       
       

       Latvija

       Swixx Biopharma SIA Tel: +371 6 616 47 50

       
       

       This leaflet was last revised in

       . There are also links to other websites about rare diseases and treatments.

       
       

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       The following information is intended for healthcare professionals only:

       
       

       Instructions for use – reconstitution, dilution and administration

       
       

       The powder for concentrate for solution for infusion has to be reconstituted with water for injections, diluted with 0.9% sodium chloride solution for injection and then administered by intravenous infusion.

       
       

       From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage and conditions are the responsibility of the user. The reconstituted solution cannot be stored and should be promptly diluted; only the diluted solution can be held for up to 24 hours at 2ºC -8ºC.

       
       

       Use aseptic technique

       
       

       1. The number of vials should be determined to be reconstituted based on the individual patient's weight and the required vials should be removed from the refrigerator in order to allow them to reach room temperature (in approximately 30 minutes). Each vial of Fabrazyme is intended for single use only.

          
          

          Reconstitution

          
          

       2. Each vial of Fabrazyme 35 mg has to be reconstituted with 7.2 ml water for injections. Forceful impact of the water for injections on the powder and foaming should be avoided. This is done by slow drop-wise addition of the water for injection down the inside of the vial and not directly onto the lyophilisate. Each vial should be rolled and tilted gently. The vial should not be inverted, swirled or shaken.

          
          

       3. The reconstituted solution contains 5 mg agalsidase beta per ml, and appears as a clear colourless solution. The pH of the reconstituted solution is approximately 7.0. Before further dilution, the reconstituted solution in each vial should be visually inspected for particulate matter and discolouration. The solution should not be used if foreign particles are observed or if the solution is discoloured.

          
          

       4. After reconstitution, it is recommended to promptly dilute the vials, to minimise protein particle formation over time.

          
          

       5. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

          Dilution

          
          

       6. Prior to adding the reconstituted volume of Fabrazyme required for the patient dose, it is recommended to remove an equal volume of 0.9% sodium chloride solution for injection, from the infusion bag.

          
          

       7. The airspace within the infusion bag should be removed to minimise the air/liquid interface.

          
          

       8. 7.0 ml (equal to 35 mg) of the reconstituted solution from each vial up to the total volume required should be slowly withdrawn for the patient dose. Filter needles should not be used and foaming should be avoided.

          
          

       9. The reconstituted solution should slowly be injected directly into the 0.9% sodium chloride solution for injection (not in any remaining airspace) to a final concentration between

          0.05 mg/ml and 0.7 mg/ml. The total volume of sodium chloride 0.9% solution for

          infusion (between 50 and 500 ml) should be determined based on the individual dose. For doses lower than 35 mg a minimum of 50 ml should be used, for doses 35 to 70 mg a minimum of 100 ml should be used, for doses 70 to 100 mg a minimum of 250 ml should be used and for doses greater than 100 mg only 500 ml should be used. The infusion bag should be gently inverted or lightly massaged to mix the diluted solution. The infusion bag should not be shaken or excessively agitated.

          
          

          Administration

          
          

       10. It is recommended to administer the diluted solution through an in-line low protein-binding

       0.2 µm filter to remove any protein particles which will not lead to any loss of agalsidase beta activity. The initial IV infusion rate should be no more than 0.25 mg/min (15 mg/hour). The infusion rate may be slowed in the event of infusion-associated reactions.

       
       

       After patient tolerance is well established, the infusion rate may be increased in increments of

       0.05 to 0.083 mg/min (increments of 3 to 5 mg/hr) with each subsequent infusion. In clinical trials with classic patients, the infusion rate was increased incrementally to reach a minimum of 2 hours. This was achieved after 8 initial infusions at 0.25 mg/min (15 mg/hr), without any IARs, change in infusion rate, or infusion interruption. A further decrease of infusion time to

       1.5 hours was allowed for patients without new IARs during the last 10 infusions or reported serious adverse events within the last 5 infusions. Each rate increment of 0.083 mg/min (~5 mg/hr) was maintained for 3 consecutive infusions, without any new IARs, change in infusion rate, or infusion interruption, before subsequent rate increases.

       
       

       For patients weighing < 30 kg, the maximum infusion rate should remain at 0.25 mg/min (15 mg/hr).

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