What it is and what it is used for

for Fabrazyme contains the active substance agalsidase beta and is used as enzyme replacement therapy in Fabry disease, where the level of α-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.

What you need to know before you take it

e 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.

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.

Pregnancy, breast-feeding and fertility There is limited experience with the use of Fabrazyme in pregnant women. As a precaution, it is preferable to avoid the use of Fabrazyme during pregnancy. Fabrazyme gets into breast milk. Discuss with your doctor the risks and benefits of breastfeeding versus continuing Fabrazyme therapy. 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'.

How to take it

Fabrazyme

such reactions from occurring. List of other side effects: Common (may affect up to 1 in 10 people):

• chest pain

• abdominal discomfort

• difficulty in breathing

• swelling face

• pallor

• joint pain

• itching

• decreased blood pressure

• abnormal tear secretion

• chest discomfort

• feeling weak

• face oedema

• tinnitus

• exacerbated difficulty in breathing

• nasal congestion

• muscle tightness

• diarrhoea

• fatigue

• redness

• flushing

• muscle pain

• pain

• increased blood pressure

• throat tightness

• sudden swelling of the face or throat

• dizziness

• oedema in extremities

• palpitations

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.

• vertigo

• decreased sensitivity to pain

• stomach discomfort

• burning sensation

• muscle spasms

• wheezing

• sleepiness

• urticaria

• increased heartbeat

• pain at the extremities

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.

• abdominal pain

• nasopharyngitis

• back pain

• hot flush

• rash

• feeling hot

• low heart rate

• hyperthermia

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.

• lethargy

• decreased mouth sensitivity

• syncope

• musculoskeletal stiffness

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.

• cough

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.

Uncommon (may affect up to 1 in 100 people):

• tremor

• skin discomfort

• red eyes

• musculoskeletal pain

• ear pain

• rhinitis

• throat pain

• influenza-like illness

• fast breathing

• malaise

• itchy rash

• low heart rate due to conduction disturbances

• feeling hot and cold

• increased sensitivity to pain

• difficulty swallowing

• upper respiratory tract congestion

• infusion site pain

• red rash

• infusion site reaction

• (mottled purplish) skin discolouration

• itching eyes

• coldness of the extremities

• ear swelling

• injection site blood clotting

• bronchospasm

• skin discolouration

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

• runny nose

• oedema

Use aseptic technique

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.

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.

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.

• heart burn

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.

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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Manufacturer Genzyme Ireland Limited, IDA Industrial Park, Old Kilmeaden Road, Waterford, Ireland This leaflet does not contain all the information about your medicine. If you have any questions or are not sure about anything, ask your doctor or pharmacist. This leaflet was last revised in March 2024

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

How to store it

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 Sanofi 410 Thames Valley Park Drive Reading Berkshire RG6 1PT UK Tel: 0800 035 2525 Email: [email protected]

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 infusionassociated reactions.

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

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. 907737