Cerezyme

Package Leaflet: Information for the User

Cerezyme 400 Units powder for concentrate for solution for infusion

Imiglucerase
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Cerezyme is and what it is used for
2. What you need to know before using Cerezyme
3. How to use Cerezyme
4. Possible side effects
5. How to store Cerezyme
6. Contents of the pack and other information

1. What Cerezyme is and what it is used for

Cerezyme contains the active substance imiglucerase and is used to treat patients with Type 1 or Type 3 Gaucher disease who have signs of the disease such as: anaemia (low number of red blood cells), tendency to bleeding (due to low platelet count – a type of blood cell), enlargement of the spleen or liver, or bone disease.
People affected by Gaucher disease have low levels of an enzyme called acid -glucosidase. This enzyme helps the body regulate levels of glucosylceramide, a natural substance in the body composed of sugars and fats. In Gaucher disease, levels of glucosylceramide can increase excessively.
Cerezyme is the artificial enzyme imiglucerase, which replaces the naturally occurring acid -glucosidase enzyme that is deficient or insufficiently active in patients with Gaucher disease.
The information contained in this package leaflet applies to all patient groups, including children, adolescents, adults and elderly people.

2. What you should know before using Cerezyme

Do not use Cerezyme:

• If you are allergic to imiglucerase or to any of the other ingredients of this medicine (listed in section 6). Warnings and precautions Talk to your doctor or pharmacist before using Cerezyme:
• if you are being treated with Cerezyme, you may develop an allergic reaction during or shortly after administration of the medicine. If you experience such a reaction, you must inform your doctor immediately. Your doctor will perform a test to determine whether you are allergic to imiglucerase.
• some patients with Gaucher disease have high blood pressure in the lung vessels (pulmonary hypertension). The cause may be unknown or related to heart, lung, or liver problems. This may occur regardless of whether the

patient is receiving treatment with Cerezyme. However, if you experience shortness of breath,
you must inform your doctor.
Other medicines and Cerezyme
Inform your doctor or pharmacist if you are taking, have recently taken, or might take
any other medicines.
Cerezyme must not be administered mixed with other medicines in the same infusion.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding,
consult your doctor or pharmacist before taking this medicine.
Cerezyme should be used with caution during pregnancy and breastfeeding.
Cerezyme contains sodium
This medicine contains 41 mg of sodium (the main component of table salt) per vial.
This corresponds to 2% of the maximum recommended daily intake of sodium for an adult.
It is administered in a 0.9% sodium chloride solution for intravenous infusion. This should
be taken into consideration in patients following a sodium-controlled diet.

3. How to use Cerezyme

Instructions for correct use

Cerezyme is administered intravenously via an infusion (intravenous infusion).

The medicine is supplied as a powder which is then mixed with sterile water before administration.
Cerezyme should only be used under the supervision of a physician experienced in the treatment of Gaucher disease. Your treating physician may recommend home therapy, provided you meet certain criteria. Please contact your treating physician if you wish to be treated at home.
Your dose will be individualized. Your doctor will determine the dosage based on the severity of your symptoms and other factors. The recommended dose is 60 units/kg body weight administered once every two weeks.
Your doctor will closely monitor your response to treatment and may adjust the dose (either increasing or decreasing it) until the optimal dose for controlling your symptoms is found.
Once the appropriate dose has been established, your doctor will continue to monitor your response periodically to ensure you are receiving the correct dose. This may occur every 6 or 12 months.
There is no available information on the effect of Cerezyme on neurological symptoms in patients with chronic neuronopathic Gaucher disease. Therefore, no specific dosing regimen can be recommended.

ICGG Gaucher Registry
You may ask your doctor to register your patient data in the "ICGG Gaucher Registry". The goals of the Registry are to improve understanding of Gaucher disease and to evaluate the effectiveness of enzyme replacement therapies, such as Cerezyme, thereby enhancing the safety and efficacy of Cerezyme use. Your data will be recorded anonymously; no one will know the information refers to you.

If you use more Cerezyme than you should
Cases of overdose have not been reported.

If you forget to use Cerezyme
If you miss an infusion, contact your doctor.
If you have any doubts about using this product, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Common (may affect up to 1 in 10 people):

• shortness of breath
• cough
• hives/localized swelling of the skin or of the internal tissues of the mouth or throat
• itching
• erythema

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

• dizziness
• headache
• sensation of tingling, prickling, burning, or numbness of the skin
• increased heart rate
• bluish skin discoloration
• hot flushes
• drop in blood pressure
• vomiting
• nausea
• abdominal cramps
• discomfort at the infusion site
• burning at the infusion site
• swelling at the infusion site
• abscess at the injection site
• chest tightness
• fever
• chills
• fatigue
• back pain

Rare (may affect up to 1 in 1,000 people):

• anaphylactoid reactions

Some side effects have been observed during or shortly after administration of the medicine. These include itching, redness, hives/localized swelling of tissues or of the mucosa of the mouth and throat, chest tightness, increased heart rate, bluish skin discoloration, shortness of breath, sensation of tingling, prickling, burning, or numbness of the skin, drop in blood pressure, and back pain. If you experience any of these symptoms, inform your doctor immediately. You may need to take other medicines to prevent an allergic reaction (e.g. antihistamines and/or corticosteroids).

Reporting of side effects

If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly through the national reporting system detailed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Cerezyme

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 that month.
Unopened vials:
Store in a refrigerator (2°C – 8°C).
Diluted solution:
Cerezyme should be used immediately after reconstitution with sterile water. The reconstituted solution in the vial must not be stored and should be promptly diluted into an infusion bag; only the diluted solution may be stored for up to 24 hours if kept refrigerated (2°C – 8°C) and protected from light.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Cerezyme contains

• The active substance is imiglucerase. Imiglucerase is a modified form of the human enzyme acid -glucosidase, produced using recombinant DNA technology. One vial contains 400 units of imiglucerase. The reconstituted solution contains 40 units of imiglucerase per ml.
• The other components are: mannitol, sodium citrate, citric acid monohydrate and polysorbate 80.

Description of the appearance of Cerezyme and contents of the pack
Cerezyme 400 Units is a white to off-white powder for concentrate for solution for infusion (supplied in vials, pack sizes of 1, 5 or 25). Not all pack sizes may be marketed. Cerezyme is supplied as a white to off-white powder. The reconstituted liquid is clear, colourless, and free from foreign particles. The reconstituted solution must be further diluted.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation 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 Authorisation Holder:

België/Belgique/Belgien
Sanofi Belgium
Tél/Tel: + 32 2 710 54 00

България
Sanofi S.r.l.
+39 02 39394275

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

Danmark
sanofi A/S
Tlf: +45 45 16 70 00

Deutschland
Sanofi-Aventis Deutschland GmbH
Tel: 0800 04 36 996
Tel. aus dem Ausland: +49 69 305 70 13

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

Ελλάδα
Sanofi-Aventis Μονοπρόσωπη AEBE
Τηλ: +30 210 900 1600

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

France
Sanofi Winthrop Industrie
Tél: 0 800 222 555
Appel depuis l’étranger : +33 1 57 63 23 23

Hrvatska

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

Ísland
Vistor hf.
Sími: +354 535 7000

Italia
Sanofi S.r.l.
Tel: 800 536 389

Κύπρος

Latvija

Lietuva

Luxembourg/Luxemburg
Sanofi Belgium
Tél/Tel: + 32 2 710 54 00

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

Malta
Sanofi S.r.l.
+39 02 39394275

Nederland
Sanofi B.V.
Tel: +31 20 245 4000

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

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

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

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

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

Slovenija

Slovenská republika

Suomi/Finland
Sanofi Oy
Puh/Tel: + 358 201 200 300

Sverige
Sanofi AB
Tel: +46 (0)8 634 50 00

United Kingdom

More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu/. In addition, links to other websites on rare diseases and their treatments are provided.

The following information is intended exclusively for healthcare professionals:

Instructions for use – Reconstitution, dilution and administration

Each vial of Cerezyme is for single use only. After reconstitution, each
vial of Cerezyme contains 400 units of imiglucerase in 10.0 ml (40 units per ml).
Determine the number of vials to be reconstituted according to the dosing regimens of individual
patients and remove the vials from the refrigerator.
Use an aseptic technique.
Reconstitution
Reconstitute each vial with 10.2 ml of Water for Injection (WFI); avoid directing a strong stream of water
onto the powder and gently mix to avoid foaming of the solution; the reconstituted volume is 10.6 ml. The pH of the reconstituted solution is approximately 6.2.
After reconstitution, it is a clear, colourless liquid, free from foreign particles. The reconstituted solution must be further diluted. Before further dilution, visually inspect the reconstituted solution in each vial for the presence of foreign particles and discoloration. Do not use vials showing foreign particles or discoloration.
After reconstitution, dilute the vials immediately and do not store for subsequent use.
Dilution
The reconstituted solution contains 40 units of imiglucerase per ml. The reconstituted volume allows accurate withdrawal of 10.0 ml (equivalent to 400 units) from each vial. Withdraw 10.0 ml of reconstituted solution from each vial and combine the withdrawn volumes. Then dilute the combined volumes with 0.9% sodium chloride solution for intravenous infusion to obtain a final volume of 100 to 200 ml. Mix the infusion solution gently.
Administration
It is recommended to administer the diluted solution through a low-protein-binding in-line filter of 0.2 µm to remove any protein particles. This will not cause any loss of imiglucerase activity. It is recommended to administer the diluted solution within 3 hours. The diluted product in 0.9% sodium chloride solution for intravenous infusion will maintain chemical stability if stored for up to 24 hours between 2°C and 8°C in the dark, but microbiological safety will depend on the reconstitution and dilution being performed under aseptic conditions.
Cerezyme does not contain preservatives. Unused product and waste material derived from this medicinal product must be disposed of in accordance with local legal requirements.