Aldurazyme 100 U/ml concentrate for solution for infusion

Aldurazyme is used to treat patients with MPS I disease (Mucopolysaccharidosis I). It is given to treat the non-neurological manifestations of the disease.

People with MPS I disease have either a low level or no level of an enzyme called ?-L-iduronidase, which breaks down specific substances (glycosaminoglycans) in the body. As a result, these substances do not get broken down and processed by the body as they should. They accumulate in many tissues in the body, which causes the symptoms of MPS I.

Aldurazyme is an artificial enzyme called laronidase. This can replace the natural enzyme which is lacking in MPS I disease.

Do not use Aldurazyme
If you are allergic (hypersensitive) to any of the ingredients of Aldurazyme or if you have experienced a severe allergic reaction to laronidase.

Take special care with Aldurazyme

If you are treated with Aldurazyme, 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 4 ?Possible Side Effects?). Some of these reactions may be severe. When you experience such a reaction, you should immediately contact your doctor.

If these reactions occur, the Aldurazyme infusion should be stopped immediately and appropriate treatment will be started by your doctor.
These reactions may be particularly severe if you have a pre-existing MPS I-related upper airway obstruction.
You may be given additional medication such as antihistamines and paracetamol to help prevent allergic-type reactions.

Using other medicines
Please inform your doctor if you use medicines containing chloroquine or procaine, due to a possible risk of decreasing the action of Aldurazyme.

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Pregnancy and breast-feeding

There is not enough experience of the use of Aldurazyme in pregnant women. Aldurazyme should not be used during pregnancy unless clearly necessary. Ask your doctor or pharmacist for advice before taking any medicine.

It is not known whether Aldurazyme appears in breast milk. It is recommended to stop breast-feeding during treatment with Aldurazyme. Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines
The effects on the ability to drive and to use machines have not been studied.

Important information about some of the ingredients of Aldurazyme

This medicinal product contains 1.29 mmol sodium per vial. To be taken into consideration by patients on a controlled sodium diet.

Instruction for use - dilution and administration
The concentrate for solution for infusion has to be diluted before administration and is for intravenous use (see information for health care professionals).
Administration of Aldurazyme should be carried out in an appropriate clinical setting where resuscitation equipment to manage medical emergencies would be readily available.

Dosage
The recommended dosage regimen of Aldurazyme is 100 U/kg body weight given once every week as an intravenous infusion. The initial infusion rate of 2 U/kg/h may be gradually increased every fifteen minutes, if tolerated, to a maximum of 43 U/kg/h. The total volume of the administration should be delivered in approximately 3-4 hours.

If you forget to use Aldurazyme

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

If you use more Aldurazyme than you should
No case of overdose of Aldurazyme has been reported.

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

Side effects were mainly seen while patients were being given the medicine or shortly after (infusion-associated reactions). If you experience any reaction like this, please tell your doctor immediately. The number of these reactions decreased the longer that patients were on Aldurazyme. The majority of these reactions were mild or moderate in intensity. However, a few patients who had a prior history of severe MPS I related upper airway and pulmonary involvement, experienced severe reactions including bronchospasm, respiratory arrest, and swelling of the face.

The following side effects have been reported:

Very common (occurring in more than 1 in 10 patients)

• headache
• nausea
• abdominal pain
• rash
• joint disease, joint pain, back pain, pain in arms or legs
• flushing
• fever
• chills
• increased heart rate
• increased blood pressure
• less oxygen in the blood
• reaction at the infusion site

Common (occurring in more than 1 in 100 patients and less than 1 in 10 patients)

• increased body temperature
• tingling
• dizziness
• cough
• difficulty in breathing which may be extreme
• vomiting
• diarrhoea
• swelling of the face or neck
• hives
• itching
• hair loss
• cold sweat, heavy sweating
• muscle pain
• low blood pressure
• paleness
• cold hands or feet
• feeling hot, feeling cold
• fatigue
• influenza like illness
• allergic reaction
• restlessness

Unknown frequency

• Bluish color of the skin (due to lower levels of oxygen in the blood)
• Fast breathing
• redness of the skin
• Leakage of the drug into the surrounding tissue at the site of injection, which may cause swelling or redness

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Keep out of the reach and sight of children.

Do not use Aldurazyme after the expiry date which is stated on the label after the letters EXP.

Unopened vials:
Store in a refrigerator (2°C ? 8°C).

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

What Aldurazyme contains

• The active substance is laronidase. One ml of the solution in the vial contains 100 U of laronidase. Each vial of 5 ml contains 500 U of laronidase.
• The other ingredients are: Sodium chloride, Sodium phosphate monobasic monohydrate, Sodium phosphate dibasic heptahydrate, Polysorbate 80, Water for injections

What Aldurazyme looks like and contents of the pack

Aldurazyme is supplied as a concentrate for solution for infusion. It is a solution that is clear to slightly opalescent, and colourless to pale yellow.

Pack size: 1, 10 and 25 vials per carton. Not all pack sizes may be marketed.

Marketing Authorisation Holder

Genzyme Europe B.V., Gooimeer 10, NL-1411 DD, Naarden, The Netherlands.

Manufacturer

Genzyme Ltd., 37 Hollands Road, Haverhill, Suffolk CB9 8PU, United Kingdom.

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

Magyarország Genzyme Europe B.V. Képviselet, Tel 36 1 310 7440 BelgiëBelgiqueBelgien Luxemburg Luxembourg Genzyme Belgium N.V., TélTel 32 2 714 17 11

Nederland Genzyme Europe B.V., Tel 31 35 6991200 Genzyme CEE GmbH . 359 2 971 1001

Österreich Genzyme Austria GmbH, Tel 43 1 774 65 38 eská republikaSlovenská RepublikaSlovenija Genzyme Czech, s.r.o., Tel 420 227 133 665

DanmarkNorgeSverigeSuomiFinland Ísland Genzyme AS, DanmarkTanskaDanmörk, TlfPuh.Sími 45 32712600 PolskaEestiLatvijaLietuva Genzyme Polska Sp. z o.o. PoolaPolijaLenkija, Tel 48 22 24 60 900

Deutschland Genzyme GmbH, Tel 49 610236740 Portugal Genzyme Portugal S.A., Tel 351 21 422 0100

Genzyme Hellas Ltd. 30 210 99 49 270 România Genzyme CEE GmbH- Reprezentana pentru România Tel 40 21 243 42 28

España Genzyme, S.A., Tel 34 91 6591670 United KingdomIreland Genzyme Therapeutics Ltd. United Kingdom Tel 44 1865 405200

France

Genzyme S.A.S.,
Tél: + 33 (0) 825 825 863

Italia/Malta

Genzyme Srl (Italia/Italja),
Tel: +39 059 349811

This leaflet was last approved in

This medicine has been authorised under ?exceptional circumstances?.
This means that because of the rarity of this disease it has been impossible to get complete information on this medicine.
The European Medicines Agency (EMEA) will review any new information on the medicine every year and this leaflet will be updated as necessary.

<-------------------------------------------------------------------------------------------------------------------------- The following information is intended for medical or healthcare professionals only:

Each vial of Aldurazyme is intended for single use only. The concentrate for solution for infusion has to be diluted with sodium chloride 9 mg/ml (0.9%) solution for infusion using aseptic technique. It is recommended that the diluted Aldurazyme solution be administered to patients using an infusion set equipped with an 0.2 µm in-line filter.

From a microbiological safety point of view, the product should be used immediately. If not used immediately, in-use storage should not be longer than 24 hours at 2°C - 8°C provided that dilution has taken place under controlled and validated aseptic conditions.

Aldurazyme should not be mixed with other medicinal products in the same infusion.

Preparation of the Aldurazyme Infusion (Use Aseptic Technique)

Determine the number of vials to be diluted based on the individual patient's weight. Remove the required vials from the refrigerator approximately 20 minutes in advance in order to allow them to reach room temperature (below 30-C).
Before dilution, visually inspect each vial for particulate matter and discoloration. The clear to slightly opalescent and colourless to pale yellow solution should be free of visible particles. Do not use vials exhibiting particles or discoloration.
Determine the total volume of infusion based on the individual patient's weight, either 100 ml (if bodyweight is less or equal than 20 kg) or 250 ml (if bodyweight is more than 20 kg) of 0.9% sodium chloride intravenous solution.
Withdraw and discard a volume of sodium chloride 9 mg/ml (0.9%) solution for infusion from the infusion bag equal to the total volume of Aldurazyme to be added.
Withdraw the required volume from the Aldurazyme vials and combine the withdrawn volumes. Add the combined volumes of Aldurazyme to the sodium chloride 9 mg/ml (0.9%) solution for infusion.
Mix the solution for infusion gently.
Prior to use visually inspect the solution for particulate matter. Only clear and colourless solutions without visible particles should be used.

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