Fabrazyme 35 mg powder for concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

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 they have the same symptoms 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 using 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, a condition in which the enzymatic activity of α-galactosidase is absent or below normal levels. In individuals affected by Fabry disease, a fatty substance called globotriaosylceramide (GL-3) is not properly cleared from the body's cells and progressively accumulates in the walls of blood vessels within organs.

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

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

2. What you need to know before using Fabrazyme

Do not use Fabrazyme

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

Warnings and precautions

Talk to your doctor or pharmacist before starting treatment with 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 or up to the end of the day of the infusion (see section 4). If you experience such a reaction, you must tell your doctor immediately. You may need additional medications to prevent these types of reactions.

Children and adolescents

Clinical studies have not been conducted in children aged 0 to 4 years. The risks and benefits of Fabrazyme have not yet been established in children aged 5 to 7 years, and therefore doses cannot be recommended for this age group.

Other medicines and Fabrazyme

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

Tell your doctor if you are taking other medicines containing chloroquine, amiodarone, benoquin, or gentamicin. There is a theoretical risk of reduced activity of agalsidase beta.

Pregnancy, breastfeeding, and fertility

Experience with the use of Fabrazyme in pregnant women is limited. As a precaution, it is preferable to avoid using Fabrazyme during pregnancy. Fabrazyme passes into breast milk. Discuss with your doctor the risks and benefits of breastfeeding versus continuing treatment with Fabrazyme. Studies examining the effects of Fabrazyme on fertility have not been conducted.

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

Driving and using machines

Do not drive or operate tools or machinery if you experience dizziness, somnolence, 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 of sodium (23 mg) per vial; hence, it is essentially “sodium-free”.

3. How to use Fabrazyme

Fabrazyme is administered by intravenous infusion (drip into a vein). 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 leaflet).

Always follow exactly your doctor's instructions for using this medicine. If you are unsure, consult your doctor again.

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

The recommended dose of Fabrazyme for adults is 1 mg/kg of body weight, administered once every 2 weeks. Dose adjustment is not required in patients with renal disease.

Use in children and adolescents

The recommended dose of Fabrazyme for children and adolescents aged 8 to 16 years is 1 mg/kg of body weight, administered once every 2 weeks. Dose adjustment is not required in patients with renal disease.

If you use more Fabrazyme than you should

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

If you forget to use Fabrazyme

If you miss an infusion of Fabrazyme, contact your doctor.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

In clinical studies, adverse effects were observed mainly while patients were receiving the infusion or shortly afterwards ("infusion-related reactions"). Serious allergic reactions, potentially life-threatening ("anaphylactic reactions"), have been reported in some patients. If you experience any serious adverse effect, 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 skin sensations such as burning or tingling. Your doctor may decide to slow down the infusion rate or administer additional medications to help prevent these reactions.

List of other adverse effects:

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

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor or nurse, even if it is a possible adverse reaction not listed in this leaflet. You may also report them directly through the national reporting system listed in Appendix V. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. Storage of Fabrazyme

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

Do not use this medicine after the expiry date stated on the label after “EXP”. The expiry date refers to the last day of the month indicated.

Unopened vials

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

Reconstituted and diluted solutions

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

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the container and other information

Composition of Fabrazyme

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

• The other components are:

• Mannitol (E421)

• Monosodium dihydrogen phosphate monohydrate (E339)

• Disodium phosphate heptahydrate (E339)

Appearance of the product and contents of the container

Fabrazyme is presented as a white to off-white powder. After reconstitution, it is a clear, colorless liquid free from foreign particles. The reconstituted solution must be further diluted before use.

Packaged contents: 1, 5 and 10 vials per carton. Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

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

Manufacturer

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

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent review of this summary:

Other sources of information

Detailed information on this medicine 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.

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 0.9% sodium chloride injection solution, and then administered by intravenous infusion.

From a microbiological standpoint, the medicine should be used immediately. If not used immediately, storage and conditions of use are the responsibility of the user. The reconstituted solution must not be stored and should be diluted without delay; only the diluted solution may be kept for up to 24 hours at 2 °C to 8 °C.

Use an aseptic technique

1. The number of vials required for reconstitution should be calculated based on the patient's weight, and the necessary vials should be removed from the refrigerator to allow them to reach room temperature (approximately 30 minutes). Each vial of Fabrazyme is for single use only.

Reconstitution

1. Each 35 mg vial of Fabrazyme must be reconstituted with 7.2 mL of water for injections. Avoid forceful impact of the water for injections onto the powder and the formation of foam. This can be achieved by slowly adding the water for injections as drops down the inner wall of the vial, not directly onto the lyophilisate. Each vial should be gently tilted and rotated. The vial must not be inverted, rolled, or shaken.

2. The reconstituted solution contains 5 mg of agalsidase beta per mL and should appear clear and colourless. The pH of the reconstituted solution is approximately 7.0. Before further dilution, visually inspect the reconstituted solution in each vial for particulate matter and discoloration. Do not use the solution if foreign particles are observed or if the solution has changed colour.

3. After reconstitution, it is recommended to dilute the vials promptly to minimize the formation of protein particles over time.

4. Any unused medicine and all materials that have come into contact with it must be disposed of in accordance with local regulations.

Dilution

1. Before adding the required volume of reconstituted Fabrazyme for the patient's dose, it is recommended to remove an equivalent volume of 0.9% sodium chloride injection solution from the infusion bag.

2. The air in the infusion bag should be removed to minimize the air/liquid interface.

3. Slowly withdraw 7.0 mL (equivalent to 35 mg) of the reconstituted solution from each vial, until the total volume required for the patient's dose is obtained. Do not use filter needles, and avoid foaming.

4. Slowly inject the reconstituted solution directly into the 0.9% sodium chloride injection solution (avoiding injection into an air space), to achieve a final concentration between 0.05 mg/mL and 0.7 mg/mL. The total volume of 0.9% sodium chloride infusion solution (between 50 and 500 mL) should be determined based on the individual dose. For doses less than 35 mg, a minimum of 50 mL should be used; for doses from 35 to 70 mg, a minimum of 100 mL should be used; for doses from 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 must not be shaken or vigorously agitated.

Administration

1. For administration of the diluted solution, it is recommended to use an in-line 0.2 µm filter with low protein binding to remove any protein particles, which will not result in any loss of agalsidase beta activity. The initial infusion (IV) rate must not exceed 0.25 mg/min (15 mg/hour). The infusion rate may be reduced in case of infusion-associated reactions (IARs).

Once the patient's tolerance has been well established, the infusion rate may be increased in increments of 0.05 to 0.083 mg/min (increments of 3 to 5 mg/h) with each subsequent infusion. In clinical trials with classic patients, the infusion rate was progressively increased to achieve a minimum infusion duration of 2 hours. This was achieved after 8 initial infusions at 0.25 mg/min (15 mg/h), with no IARs, no changes in infusion rate, and no interruptions. A further reduction in infusion time to 1.5 hours was permitted for patients without new IARs during the last 10 infusions or without serious adverse events reported during the last 5 infusions. Each increase in infusion rate of 0.083 mg/min (~5 mg/h) was maintained for 3 consecutive infusions, with no new IARs, no changes in infusion rate, and no interruptions, before subsequent rate increases.

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