Label: information for the user

Fabrazyme 35mg powder for concentrate for solution for infusion.

agalsidasa beta

Read this label carefully before starting to use this medication, because it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medication has been prescribedonlyto you,and you should not give it to other people even ifthey havethe same symptomsas you, as it may harm them.
• Ifyou experienceadverse effects, consult your doctor or pharmacist,even ifthey do not appearin this label.See section 4.

Fabrazyme contains the active ingredient agalsidase beta and is used as enzyme replacement therapy in Fabry disease, in which the level of enzyme activity of alpha-galactosidase is non-existent or below normal.

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

Fabrazymeis indicated for use in adults, adolescents, and children 8 years of age or older.

Do not use Fabrazyme

• if you are allergic to agalsidase beta or any of the other components of this medicine (listed in section6).

Warnings and precautions

Consult your doctor or pharmacist before starting to use Fabrazyme.

If you are being treated with Fabrazyme, you may develop infusion-related reactions. An infusion-related reaction is any adverse effect that occurs during the infusion or up to the end of the day of the infusion (see section 4). If you experience a reaction like this, you musttell your doctor immediately. You may need other medicines to prevent this type of reaction.

Children and adolescents

No clinical studies have been conducted in children aged0 to4 years. The risks and benefits of Fabrazyme have not yet been established in children aged 5 to 7 years, and therefore no doses can be recommended for this age group.

Other medicines and Fabrazyme

Inform your doctororpharmacistifyouare taking,have takenrecentlyor may need to take any other medicine.

Inform your doctor if you are using other medicines that containchloroquine, amiodarone,benoquin or gentamicin. There is a theoretical risk of reduced agalsidase beta activity.

Pregnancy, breastfeeding and fertility

The experience with the use of Fabrazyme in pregnant women is limited. As a precaution, it is preferable to avoid the use of Fabrazyme during pregnancy. Fabrazyme passes into breast milk.Discuss the risks and benefits of breastfeeding versus continuing treatment with Fabrazyme with your doctor.No studies have been conducted to examine the effects of Fabrazyme on fertility.

If you are pregnant or breastfeeding, or think you may be pregnant or intend to become pregnant, consult your doctor or pharmacist before using this medicine.

Driving and operating machinery

Do not drive or operate tools or machinery if you experience dizziness, drowsiness, vertigo or fainting during or shortly after the administration of Fabrazyme (see section 4). First, talk to your doctor.

Fabrazyme contains sodium

This medicine contains less than 1mmol of sodium (23 mg) per vial; it is essentially “sodium-free”.

Fabrazyme is administered through an intravenous infusion. It is supplied as a powder that will be mixed with sterile water before administration (see information for healthcare professionals at the end of this prospectus).

Follow exactly the administration instructions for this medication as indicated by your doctor. If in doubt, consult your doctor again.

Fabrazyme is only used under the supervision of a doctor experienced in the treatment of Fabry disease. If you meet certain criteria, your doctor may consider that you can receive the treatment at home. Contact your doctor if you wish to receive the treatment at home.

The recommended dose of Fabrazyme for adults is 1 mg/kg of body weight, once every 2 weeks. It is not necessary to adjust the dose in patients with renal disease.

Use in children and adolescents

The recommended dose of Fabrazyme for children and adolescents from 8 to 16 years old is 1 mg/kg of body weight, once every 2 weeks. It is not necessary to adjust the dose in patients with renal disease.

If you use more Fabrazyme than you should

It has been shown that doses of up to 3 mg/kg of body weight are safe.

If you forgot to use Fabrazyme

If you have forgotten a Fabrazyme infusion, contact your doctor.

If you have any other questions about the use of this medication, ask your doctor.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

In clinical studies, side effects were mainly observed while patients were receiving the medicine or shortly after (“perfusion-related reactions”). Severe allergic reactions (anaphylactic reactions) potentially fatal have been reported in some patients. If you experience any severe side effect,contact your doctor immediately.

Some very common symptoms (may affect more than 1 in 10 people) include chills, fever, feeling cold, nausea, vomiting, headaches, and abnormal skin sensations such as burning or tingling. Your doctor may decide to reduce the infusion rate or administer additional medications to prevent such reactions from occurring.

List of other side effects:

In some patients initially treated with the recommended dose and whose dose was subsequently reduced during an additional period, certain symptoms of Fabry's disease were observed more frequently.

Reporting of side effects

If you experience any type of side effect, consult your doctor or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keepthis medicationout of sightand out of reachof children.

Do not usethis medicationafter the expiration date that appears onthe label after “CAD”. The expiration date is the last day of the month indicated.

Unopened vials

Store in refrigerator (between 2 °C and 8 °C).

Reconstituted and diluted solutions

The reconstituted solution should not be stored and should be diluted quickly. The diluted solution can be kept for a maximum of 24 hours at a temperature between 2 °C and 8 °C.

Medicines should not be thrown away through drains or in the trash..Ask your pharmacisthow to dispose of the containers and medicationsthat you no longer need.This will help protect the environment.

Composition of Fabrazyme

• The active ingredient is agalsidase beta, a vial contains 35 mg. After reconstitution, each vial contains 5 mg of agalsidase beta per ml.
• The other components are:

• Manitol (E421)
• Dihidrogenofosfato de sodio monohidrato (E339)
• Fosfato de disodio heptahidrato (E339)

Appearance of the product and contents of the pack

Fabrazyme is presented as a white to off-white powder. After reconstitution, it is a transparent, colorless, particle-free liquid. The reconstituted solution must be diluted subsequently.

Contents of the packs: 1, 5 and 10 vials per box. Some pack sizes may only be marketed.

Marketing authorization holder and responsible person for manufacturing

Marketing authorization holder

Sanofi B.V.,Paasheuvelweg 25, 1105 BP Amsterdam, Netherlands.

Responsible person for manufacturing

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

Further information on this medicinal product can be obtained by contacting the local representative of the marketing authorization holder:

Last update of thissummary of product characteristics:

Other sources of information

The detailed information on this medicinal product is available on the website of the European Medicines Agency:http://www.ema.europa.eu. There are also links to other websites on rare diseases and orphan medicinal products.

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This information is intended for healthcare professionals only

Instructions for use – reconstitution, dilution and administration

The powder for concentrate for solution for infusion must be reconstituted with water for injections, diluted with sodium chloride 0.9% solution and then administered viaintravenous infusion.

From a microbiological point of view, the medicinal product should be used immediately. If not used immediately, the storage and handling conditions are the responsibility of the user. The reconstituted solution cannot be stored and must be diluted without delay; only the diluted solution can be kept for up to 24hours at 2 ºC to 8 ºC.

Use aseptic technique

1. The number of vials required for reconstitution must be calculated according to the weight of each patient and the required vials must be removed from the refrigerator to allow them to reach room temperature (approximately 30 minutes). Each vial of Fabrazyme is for single use.

Reconstitution

1. Each vial of Fabrazyme 35mg must be reconstituted with 7.2ml ofwater for injections. The water for injections must be added slowly to the powder to avoid splashing and foaming. This is achieved by adding the water for injections slowly through the inner wall of the vial and not directly onto the lyophilisate. Each vial must be tilted and gently rotated. The vial must not be inverted, turned or shaken.

1. The reconstituted solution, containing 5mg of agalsidase beta per ml, is transparent and colorless. The pH of the reconstituted solution is approximately 7.0. Before diluting, the reconstituted solution from each vial must be visually checked to ensure that it does not contain particles or has changed color. The solution must not be used if particles are observed or if the solution has changed color.

1. After reconstitution, it is recommended todilute the vials quicklyto minimize the formation of protein particles over time.

1. The elimination of unused medicinal product and all materials that have been in contact with it will be carried out in accordance with local regulations.

Dilution

1. Before adding the reconstituted volume of Fabrazyme required for the patient's dose, it is recommended to remove an equivalent volume ofsodium chloride 0.9% solutionfrom the infusion bag. The air contained in the infusion bag must be removed to minimize the air/liquid interface.

1. The reconstituted solution must be slowly extracted from each vial until the required volume for the patient's dose is reached. No filter needles must be used and the formation of foam must be avoided.

1. The reconstituted solution must be slowly injected directly into thesodium chloride 0.9% solution(avoiding injection into an air space) until a final concentration between 0.05 mg/ml and 0.7 mg/ml is achieved. The total volume of the sodium chloride 0.9% solution (between 50 and 500 ml) must be determined based on the individual dose. For doses less than 35 mg, a minimum of 50 ml must be used, for doses of35 to70 mg, a minimum of 100 ml must be used, for doses of70 to100 mg, a minimum of 250 ml must be used and for doses greater than 100 mg, only 500 ml must be used. The infusion bag must be gently inverted or massaged to mix the diluted solution. The infusion bag must not be shaken or agitated excessively.

Administration

10.To administer the diluted solution, it is recommended to use an in-line filter with a pore size of 0.2?m with low protein binding to the plasma proteins to eliminate any protein particles, which will not result in any loss of agalsidase beta activity. The initial infusion rate (IV) must not exceed 0.25mg/min (15mg/hour). The infusion rate can be reduced in case of infusion-related reactions (IRRs).

Once the patient's tolerance has been well established, the infusion rate can be increased in increments of 0.05 to 0.083mg/min (increments of 3 to 5mg/h) with each subsequent infusion. In clinical trials with classical patients, the infusion rate was increased progressively to a minimum of 2 hours. This was achieved after 8 initial infusions at 0.25mg/min (15mg/h), without any IRRs, without a change in infusion rate or without interruption of infusion. An additional reduction in infusion time to 1.5hours was allowed for patients without new IRRs during the last 10 infusions or without severe adverse events reported during the last 5 infusions. Each increase in infusion rate of 0.083mg/min (~5mg/h) was maintained for 3 consecutive infusions, without new IRRs, without a change in infusion rate or without interruption of infusion, before subsequent increases in infusion rate.

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