Myozyme - patient leaflet, side effects, dosage

1. What Myozyme is and what it is used for

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 alpha-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 of glycogen can get too high.

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

2. What you need to know before you are given Myozyme

Do not use Myozyme:

If you have experienced life-threatening allergic (hypersensitive) reactions to alglucosidase alfa or any of the other ingredients of this medicine (listed in section 6) and re-administration of the medicine was not successful. Symptoms of life-threatening allergic reactions include, but are not limited to, low blood pressure, very fast heart rate, difficulty breathing, vomiting, facial swelling, hives or rash.

Warnings and Precautions

If you are treated with Myozyme, you may experience an infusion-associated reaction while you are being given the medicine or during the hours following the infusion. Such a reaction comprises different symptoms like low blood pressure, chest discomfort, throat tightness, face, lips or tongue swelling (angioedema), hives (urticaria), dizziness, rash, itchy skin, nausea, vomiting, cough and bronchospasm (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 pre-treatment medicines to prevent an allergic reaction (e.g. antihistamines and/or corticosteroids) or to reduce fever (antipyretics). In studies doctors have used medicines to suppress the immune system to reduce the production of antibodies. Because you have Pompe disease, there is a risk that you get a severe infection of your airways or lungs. Using these medicines to suppress the immune system may further increase this risk.

If you experience severe ulcerative lesions of your skin, please inform your doctor. If you experience swelling of your lower limbs or generalized swelling, 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.

Other medicines and Myozyme

Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.

Pregnancy and breast-feeding and fertility

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. If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this 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.

Myozyme contains sodium

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

• 3. How Myozyme is given

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 and adolescents

The recommended dosage of Myozyme in children and adolescents 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 given more Myozyme than you should

There is no experience with overdose of Myozyme.

If you forget to use Myozyme

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

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

4. Possible side effects

Like all medicines, this medicine 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 were serious or life-threatening. 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, lip or tongue swelling, hives or rash. Some patients have experienced infusion related side effects in the form of flu-like symptoms, which lasted for a few days after completion of the infusion.

Should you experience any reaction like this, please tell your doctor immediately. You may need to be given pre-treatment medicines to prevent an allergic reaction (e.g. antihistamines and/or corticosteroids) or to reduce fever (antipyretics).

Very common: may affect more than 1 in 10 people

• 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: may affect up to 1 in 10 people

• 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: frequency cannot be estimated from the available data

• Swelling around the eyes
• Abnormal breathing sounds, including a whistling sound
• Difficulty in breathing (including shortness of breath)
• Cold extremities (e.g. hands, feet)
• Low blood pressure
• Narrowing of the blood vessels causing blood flow to be decreased
• Sudden constriction of bronchi restricting air going in and out the lungs (bronchospasm)
• 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
• Protein loss in urine
• Nephrotic Syndrome: swelling of lower limbs, generalized swelling and protein loss in urine
• Swelling and thickening of the skin at infusion site in case of leakage of the product outside

blood vessels

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine

5. How to store Myozyme

Keep this medicine out of the sight and reach of children

Do not use this medicine after the expiry date which is stated on the label 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 8°C when stored under protection from light.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

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 (E421),
• sodium dihydrogen phosphate monohydrate (E339)
• disodium phosphate heptahydrate (E339)
• polysorbate 80 (E433).

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.

Paasheuvelweg 25

1105 BP Amsterdam

The Netherlands

Manufacturer

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

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

België/Belgiqu­e/Belgien/ Luxembourg/Lu­xemburg Sanofi Belgium

Lietuva Swixx Biopharma UAB Tel. +370 5 236 91 40

Tél/Tel: + 32 2 710 54 00

Etnrapua Swixx Biopharma EOOD Ten.: +359 (0)2 4942 480	Magyarorszag SANOFI-AVENTIS Zrt. Tel: +36 1 505 0050
Česká republika sanofi-aventis, s.r.o. Tel: +420 233086 111	Malta Sanofi S.r.l. Tel: +39 02 39394275
Danmark Sanofi A/S Tlf: +45 45 16 70 00	Nederland Genzyme Europe B.V. Tel: +31 20 245 4000
Deutschland Sanofi-Aventis Deutschland GmbH Tel.: 0800 04 36 996 Tel. aus dem Ausland: +49 69 305 70 13	Norge sanofi-aventis Norge AS Tlf: + 47 67 10 71 00

Eesti Swixx Biopharma OÜ Tel. +372 640 10 30	Österreich sanofi-aventis GmbH Tel: + 43 1 80 185 – 0
EXÀàôa sanofi-aventis AEBE Tql: +30 210 900 1600	Polska sanofi-aventis Sp. z o.o. Tel.: +48 22 280 00 00
España sanofi-aventis, S.A. Tel: +34 93 485 94 00	Portugal Sanofi – Produtos Farmacéuticos, Lda. Tel: +351 21 35 89 400
France sanofi-aventis France Tél: 0 800 222 555 Appel depuis l’étranger: +33 1 57 63 23 23	Romania Sanofi Romania SRL Tel: +40 (0) 21 317 31 36
Hrvatska Swixx Biopharma d.o.o. Tel: +385 1 2078 500	Slovenija Swixx Biopharma d.o.o. Tel: +386 1 235 51 00
Ireland Sanofi-aventis Ireland Ltd. T/A SANOFI Tel: +353 (0) 1 403 56 00	Slovenská republika Swixx Biopharma s.r.o. Tel.: +421 2 208 33 600
Ísland Vistor hf. Sími: +354 535 7000	Suomi/Finland Sanofi Oy Puh/Tel: + 358 201 200 300

Sverige

Sanofi AB

Tel: +46 (0)8 634 50 00

United Kingdom (Northern Ireland) sanofi-aventis Ireland Ltd. T/A SANOFI Tel +44 (0) 800 035 2525

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site:. There are also links to other websites about rare diseases and treatments.

The following information is intended for 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