Myozyme 50 mg powder for concentrate for solution forinfusion

Myozyme is used to treat adults, children and adolescents of all ages who have a confirmed diagnosis of Pompe disease.

People with Pompe disease have low levels of an enzyme called ?-glucosidase. This enzyme helps the body control levels of glycogen (a type of carbohydrate). Glycogen provides the body with energy, but in Pompe disease the levels can get too high.

Myozyme is an artificial enzyme called alglucosidase alfa ? this can replace the natural enzyme which is lacking in Pompe disease.

In patients with late-onset Pompe disease (typically a more slowly progressive form of Pompe disease with onset of symptoms after infancy) the evidence of efficacy is limited.

You should not be given Myozyme
If you have experienced life-threatening allergic (hypersensitive) reactions to alglucosidase alfa or any of the other ingredients of Myozyme and re-administration of the medicine was not successful. Symptoms of life-threatening allergic reactions include low blood pressure, very fast heart rate, difficulty breathing, vomiting, facial swelling, hives or rash.

Take special care with Myozyme

If you are treated with Myozyme, you may experience a so-called infusion-associated reaction while you are being given the medicine or during the next 2 hours. Such a reaction comprises different symptoms like feeling hot, chills, headache, dizziness, itchy skin and nausea (see section 4 for an overview of all infusion-associated reactions). An infusion-associated reaction can sometimes be very severe. If you experience a reaction like this, you should tell your doctor immediately. You may need to be given additional medicines to prevent an allergic reaction (e.g. antihistamines and/or corticosteroids) or to reduce fever (antipyretics).

If you experience severe ulcerative lesions of your skin, please inform your doctor. Your doctor should consider discontinuation of the administration of Myozyme and initiate appropriate medical treatment. Your doctor should consider the risks and benefits of re-administering Myozyme.

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

Pregnancy and breast-feeding

There is no experience of the use of Myozyme in pregnant women. You should not be given Myozyme during pregnancy unless clearly necessary. You are recommended to stop breast-feeding when you are given Myozyme. Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Take care when driving or using any tools or machines shortly after infusion of Myozyme, since you may experience dizziness.

Important information about some of the ingredients of Myozyme

This medicine contains less than 1 mmol sodium (23 mg) per vial, i.e. essentially ?sodium free-.

Myozyme will be given to you under the supervision of a doctor who is experienced in the treatment of Pompe disease.

The dose you receive is based on your body weight. The recommended dosage of Myozyme is 20 mg per kg of body weight. It will be given to you once every 2 weeks.

Use in children
The recommended dosage of Myozyme in children is the same as in adults.

Instructions for proper use

Myozyme 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.

If you are givenmore Myozyme than needed
There is no experience with overdose of Myozyme.

If you miss an infusion of Myozyme
If you have missed an infusion, please contact your doctor.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

Like all medicines, Myozyme 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 related effects?). Some of these infusion related side effects became serious. Life threatening reactions, including very severe generalised allergic reactions and anaphylactic shock, have been reported in some patients. Symptoms of such reactions include low blood pressure, very fast heart rate, difficulty breathing, vomiting, facial swelling, hives or rash. Should you experience any reaction like this, please tell your doctor immediately. You may need to be given additional medicines to prevent an allergic reaction (e.g. antihistamines and/or corticosteroids) or to reduce fever (antipyretics).

The frequency of possible side effects listed below is defined using the following convention:

Very common affects more than 1 user in 10 Common affects 1 to 10 users in 100 Uncommon affects 1 to 10 users in 1,000 Rare affects 1 to 10 users in 10,000 Very rare affects less than 1 user in 10,000 Not known frequency cannot be estimated from the available data.

Very common:

Hives
Rash
Increased heart rate
(Facial) flushing
Fever or increased body temperature
Cough
Increased breathing rate
Vomiting
Low level of oxygen in the blood

Common Paleness Increased or high blood pressure Bluish discolouration of the skin Chills Agitation Tremor Headache Tingling Pain or local reaction at the site of the drip Dizziness Irritability Itchy skin Retching Swelling of the face, swelling of the throat or severe combined swelling of the face, throat and tongue due to a severe allergic reaction Swelling of the arms and legs Nausea Chest discomfort Throat tightness Diarrhoea Tiredness Muscle pain Muscle spasms Severe ulcerative lesions of the skin Redness of the skin

Not known:

Swelling around the eyes
Abnormal breathing sounds

Difficulty in breathing including shortness of breath Cold extremities e.g. hands, feet Low blood pressure Sudden constriction of bronchi restricting air going in and out the lungs Feeling hot Increased sweating Eyes tearing Mottled skin Restlessness Wheezing Decreased heart rate Heart stopping Chest pain not in the heart Inflammation of membrane that covers eyeball and eyelid Abdominal pain Joint pain Temporary suspension or sudden cessation of breathing

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

You should not be given Myozyme after the expiry date which is stated on the labelling after ?EXP?. The expiry date refers to the last day of that month.

Store in a refrigerator (2°C ? 8°C).

After dilution, an immediate use is recommended. However, chemical and physical in-use stability has been demonstrated for 24 hours at 2 to 8C when stored under protection from light.

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 Myozyme contains

• The active substance is alglucosidase alfa. One vial contains 50 mg of alglucosidase alfa. After reconstitution, the solution contains 5 mg of alglucosidase alfa per ml and after dilution, the concentration varies from 0.5 mg to 4 mg/ml.
• The other ingredients are
• mannitol,
• sodium dihydrogen phosphate monohydrate
• disodium phosphate heptahydrate
• polysorbate 80

What Myozyme looks like and contents of the pack

Myozyme is a powder for concentrate for solution for infusion in a vial (50 mg/vial). Each pack contains 1, 10 or 25 vials. Not all pack sizes may be marketed.

The powder is white to off-white. After reconstitution it is a clear, colourless to pale yellow solution, which may contain particles. The reconstituted solution must be further diluted.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder
Genzyme Europe B.V., Gooimeer 10, 1411 DD, Naarden, The Netherlands

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

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

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

ItaliaMalta Genzyme Srl ItaliaItalja, Tel 39 059 349811 BelgiëBelgiqueBelgien LuxemburgLuxembourg Genzyme Belgium N.V., Tel Tél 32 2 714 17 11

Magyarország Genzyme Europe B.V. Képviselet, Tel 36 1 310 7440 Genzyme CEE GmbH, . 359 2 971 1001

Nederland Genzyme Europe B.V., Tel 31 35 699 1200 eská RepublikaSlovenská Republika Slovenija Genzyme Czech s.r.o., Tel 420 221 722 511

Österreich Genzyme Austria GmbH, Tel 43 1 774 65 38 DanmarkNorgeSverigeSuomiFinland Ísland Genzyme AS, DanmarkTanskaDanmörk, TlfPuh.Sími 45 32 71 2600

Deutschland Genzyme GmbH, Tel 49 610236740 PolskaEestiLatvijaLietuva Genzyme Polska Sp. z o.o. PoolaPolijaLenkija, Tel 48 22 24 60 900

Genzyme Hellas Ltd. , 30 210 99 49 270 Portugal Genzyme Portugal S.A., Tel 351 21 422 0100

España Genzyme, S.L.U., Tel 34 91 6591670 România Genzyme CEE GmbH- Reprezentana pentru România, Tel 40.21.243.42.28

France Genzyme S.A.S., Tél 33 0 825 825 863 United KingdomIreland Genzyme Therapeutics Ltd United Kingdom, Tel 44 1865 405200

This leaflet was last approved in

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

Instructions for use ? reconstitution, dilution and administration

Myozyme has to be reconstituted with water for injections, then diluted with sodium chloride 9 mg/ml (0.9%) solution for injection and then administered by intravenous infusion. Reconstitution and dilution should be performed in accordance with good practice rules, particularly for the respect of asepsis.

Due to the proteinaceous nature of the product, particle formation may occur in the reconstituted solution and final infusion bags. Therefore, a 0.2 micron low protein binding in-line filter should be used for administration. It was demonstrated that the use of a 0.2 micron in-line filter removes visible particles and does not result in an apparent loss of protein or activity.

Determine the number of vials to be reconstituted based on the individual patient?s dose regimen (mg/kg) and remove the required vials from the refrigerator in order to allow them to reach room temperature (approximately 30 minutes). Each vial of Myozyme is for single use only.

Use aseptic technique

Reconstitution

Reconstitute each 50 mg vial of Myozyme with 10.3 ml water for injections using a syringe with a needle diameter not larger than 20 gauge. Add the water for injections by slow drop-wise addition down the side of the vial and not directly onto the lyophilised cake. Tilt and roll each vial gently. Do not invert, swirl or shake the vial. The reconstituted volume is 10.5 ml containing 5 mg enzyme/ml, and appears as a clear, colourless to pale yellow solution which may contain particles in the form of thin white strands or translucent fibres. Perform an immediate inspection of the reconstituted vials for particulate matter and discoloration. If upon immediate inspection foreign particles other than those described above are observed, or if the solution is discoloured, do not use. The pH of the reconstituted solution is approximately 6.2.

After reconstitution it is recommended to promptly dilute the vials (see below).

Dilution

When reconstituted as above, the reconstituted solution in the vial contains 5 mg alglucosidase alfa per ml. The reconstituted volume allows accurate withdrawal of 10.0 ml (equal to 50 mg) from each vial. This should then be further diluted as follows: Slowly withdraw the reconstituted solution from each vial until the volume for the patient?s dose is obtained using a syringe with a needle diameter not larger than 20 gauge. The recommended final concentration of alglucosidase in the infusion bags ranges from 0.5 mg/ml to 4 mg/ml. Remove airspace within the infusion bag. Also remove an equal volume of sodium chloride 9 mg/ml (0.9%) solution for injection, that will be replaced with reconstituted Myozyme. Slowly inject the reconstituted Myozyme directly into the sodium chloride 9 mg/ml (0.9%) solution for injection. Gently invert or massage the infusion bag to mix the diluted solution. Do not shake or excessively agitate the infusion bag.

The final infusion solution should be administered as close to preparation time as possible.

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

Administration

It is recommended to start the administration of the diluted solution within three hours. The total time between reconstitution and completion of the infusion should not exceed 24 hours.

The recommended dose regimen of Myozyme is 20 mg/kg of body weight administered once every 2 weeks as an intravenous infusion.

Infusions should be administered incrementally. It is recommended that the infusion begin at an initial rate of 1 mg/kg/h and be gradually increased by 2 mg/kg/h every 30 minutes if there are no signs of IARs (Infusion Associated Reactions) until a maximum rate of 7 mg/kg/h is reached.