Label: information for the user

Myozyme 50mg powder for concentrate for solution for infusion

Alglucosidase alfa

Read this label carefully before starting to use this medication, because it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this label. See section4.

Myozyme is used for the treatment of adults, children, and adolescents of all ages with a confirmed diagnosis of Pompe disease.

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

Myozyme contains an artificial enzyme called alglucosidase alpha that can replace the missing natural enzyme in Pompe disease (acid maltase).

No use Myozyme:

If you have experienced potentially fatal allergic reactions (hypersensitivity) to alglucosidase alfa or any of the other components of this medication (listed in section6) and if a new administration of the medication was not successful. Symptoms of potentially fatal allergic reactionsinclude, among others, low blood pressure, very rapid heart rate, difficulty breathing, vomiting, facial swelling, urticaria, or rashes.

Warnings and precautions

If you are being treated with Myozyme, you may experience a reaction associated with perfusion while the medication is being administered or during the hours after perfusion. This reaction consists of various symptoms such as low blood pressure, chest discomfort, throat constriction, facial swelling, lip or tongue swelling (angioedema), urticaria, dizziness, rashes, skin pruritus, nausea, vomiting, cough, and bronchospasm (see section4 for a general overview of all perfusion-associated reactions). The perfusion-associated reaction can sometimes be very severe. If you experience a reaction like this, you mustnotify yourdoctor immediately. You may need to receive pre-treatment medications to prevent an allergic reaction (e.g., antihistamines and/or corticosteroids) or to reduce fever (antipyretics).

In studies, doctors have used medications to suppress the immune system and reduce the production of antibodies. Since you have Pompe disease, there is a risk that you will acquire a severe respiratory or lung infection. The use of these medications to suppress the immune system may increase this risk even further.

If you observe severe skin ulcers, contact your doctor. If you observe swelling of the lower extremities or generalized swelling, contact your doctor. Your doctor should consider suspending treatment with Myozyme and initiating appropriate medical treatment. Your doctor should evaluate the benefits and risks of restarting treatment with Myozyme.

Use of Myozyme with other medications

Inform your doctor or pharmacist if you are using, have recently used, or may need to use any other medication.

Pregnancy, breastfeeding, and fertility

There is limited experience with the use of Myozyme in pregnant women. Myozyme should not be used during pregnancy unless it is clearly necessary. Inform your doctor if you are breastfeeding. There is limited experience suggesting that Myozyme passes into human breast milk in very small quantities. No effects are expected in the breastfeeding infant. Therefore, breastfeeding can be considered during treatment. However, you may consult with your doctor if you should interrupt breastfeeding as a precaution during the first 24 hours after each dose of Myozyme.If you are pregnant or breastfeeding, think you may be pregnant, or intend to become pregnant, consult your doctor or pharmacist before using this medication.

Driving and operating machines

Be careful if you drive or use tools or machines shortly after Myozyme perfusion, as you may experience dizziness, drowsiness, tremors, and/or low blood pressure.

Myozyme contains sodium

This medication contains less than 1 mmol (23mg) of sodium per vial; it is essentially “sodium-free”.

Myozyme should only be used under the supervision of a doctor with experience in treating patients with Pompe disease.

The dose you should receive varies depending on your body weight. The recommended dose of Myozyme is 20mg/kg of body weight, administered once every 2weeks.

Home Infusion

Your doctor may consider that you can receive home infusion ofMyozymeif it is safe and convenient to do so.If you experience any type of adverse effect during a Myozyme infusion, the home infusion administrator may interrupt the infusion and start the appropriate medical treatment.

Use in Children and Adolescents

The recommended dose of Myozyme in children and adolescents is the same as in adults.

Instructions for Proper Use

Myozyme is administered through a drip in a vein (intravenous infusion). This medication is provided in the form of a powder that must be mixed with sterile water before administration.

If You Use More Myozyme Than You Should

If you are administered Myozyme at a higher dose or infusion rate than recommended, you may experience reactions associated with infusion. Such a reaction may include symptoms such as:

• skin and lips turn blue due to lack of oxygen in body tissues, increased heart rate, palpitations
• difficulty breathing, coughing
• dizziness, headache, altered taste
• high blood pressure, hot flashes
• swelling of the tongue, vomiting, diarrhea, feeling of discomfort (nausea)

• chest pain, discomfort in the chest, feeling of constriction in the throat, fever, chills, feeling of coldness, andredness at the infusion site

• muscle pain
• redness of the skin

If you experience a reaction of this type, you must inform your doctor immediately (see section 2). The infusion rate will be reduced or the infusion will be stopped and, as necessary, you may receive corrective treatment.

If You Forget to Use Myozyme

If you have forgotten a infusion, contact your doctor.

If you have any other questions about the use of this medication, ask your doctor, pharmacist, or nurse.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

The side effects were mainly observed at the time when patients were receiving the medicine or shortly after ("perfusion-related side effects"). Some of these perfusion-related side effects were severe or potentially fatal. In some patients, potentially fatal reactions were observed, such as severe generalised allergic reactions and anaphylactic shock. Among the symptoms of these reactions were low blood pressure, very rapid heart rate, difficulty breathing, vomiting, swelling of the face, lips, or tongue, urticaria, or rashes.Some patients experienced perfusion-related side effects in the form of pseudogripal symptoms, which lasted for a few days after the perfusion ended.

If you experience a reaction of this type,inform your doctor immediately. You may need the administration of pre-treatment medications 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

• Urticaria (itching)
• Rash
• Increased heart rate
• Flushes (facial)
• Fever or elevated body temperature
• Cough
• Increased respiratory rate
• Vomiting
• Low oxygen levels in the blood

Common: may affect up to 1 in 10 people

• Pallor
• High or increased blood pressure
• Blue discoloration of the skin
• Chills
• Restlessness
• Tremors
• Headache
• Tickling
• Pain or local reaction at the infusion site
• Dizziness
• Irritability
• Pruritus (skin itching)
• Hiccup
• Swelling of the face, throat, or tongue due to a severe allergic reaction
• Swelling of the arms and legs
• Nausea
• Chest discomfort
• Throat constriction
• Diarrhea
• Fatigue
• Muscle pain
• Muscle spasms
• Severe skin ulcers
• Skin redness

Frequency not known: cannot be estimated from available data

• Swelling around the eyes
• Asthma
• Abnormal respiratory sounds, including wheezing
• Difficulty breathing (including dyspnea)
• Cold extremities (i.e., hands and feet)
• Low blood pressure or decreased
• Narrowing of blood vessels causing decreased blood circulation
• Sudden constriction of the bronchi that restricts the air entering and leaving the lungs (bronchospasm)
• Sensation of heat
• Sensation of cold
• Sensation of general discomfort (discomfort)
• Sensation of weakness
• Drowsiness
• Fainting
• Sensation of burning
• Increased sweating
• Lacrimation
• Mottled skin
• Restlessness
• Wheezing
• Irritation of the throat
• Lack of oxygen in the body tissues
• Decreased heart rate
• Cardiac arrest
• Strong heartbeats that may be rapid or irregular (palpitations)
• Chest pain (not heart-related)
• Inflammation of the membrane covering the eyeball and eyelid
• Abdominal pain
• Indigestion
• Difficulty swallowing
• Joint pain
• Temporary or sudden cessation of breathing
• Protein loss in the urine
• Nephrotic syndrome: swelling of the lower extremities, generalised swelling, and protein loss in the urine
• Swelling and thickening of the skin at the infusion site in case of extravasation of the medicine outside the blood vessels
• Redness of the palms
• Transient skin discoloration
• Redness at the infusion site
• Blisters (rash) at the infusion site
• Itching at the infusion site
• Bubble

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the label after "CAD". The expiration date is the last day of the month indicated.

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

After dilution, it is recommended to use immediately. However, chemical and physical stability has been demonstrated for 24hours, if maintained at a temperature between 2°C and 8°C and stored in a protected place from light.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of empty containers and unused medications. This will help protect the environment.

Myozyme Composition

• The active ingredient is alglucosidase alfa. A vial contains 50mg of alglucosidase alfa. After reconstitution, the solution contains 5mg of alglucosidase alfa per ml, and after dilution, the concentration varies from 0.5mg to 4mg/ml.
• The other components are:

• mannitol (E421)
• sodium dihydrogen phosphate monohydrate (E339)
• disodium phosphate heptahydrate (E339)
• polysorbate80 (E433).

Appearance of Myozyme and packaging contents

Myozyme is a lyophilized powder for solution for intravenous infusion in a vial (50mg/vial). Each pack contains 1, 10, or 25vials. Only some pack sizes may be marketed.

Thepowder is white or off-white. After reconstitution, the solution is transparent, colorless to pale yellow, and may contain particles. The reconstituted solution must be further diluted.

Marketing authorization holder and manufacturer

Marketing authorization holder

Sanofi B.V.

Paasheuvelweg 25

1105 BP Amsterdam

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:

Last update of this leaflet:

The detailed information on this medicinal product 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.

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This information is intended solely for healthcare professionals:

Instructions for use - reconstitution, dilution, and administration

Myozyme must be reconstituted with water for injectionsand, subsequently, diluted with a sodium chloride solution containing 9mg/ml (0.9%) for intravenous infusion. Reconstitution and dilution must be performed in accordance with good manufacturing practice, particularly in terms of asepsis.

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

Calculate the number of vials required for reconstitution based on the dosing regimen (mg/kg) for each patient and remove the required vials from the refrigerator to allow them to equilibrate to room temperature (approximately 30minutes). Each vial of Myozyme is for single use.

Use aseptic technique

• Reconstitution

Reconstitute each vial of Myozyme with 10.3ml of water for injectionsusing a syringe with a needle diameter not exceeding 20 gauge. Add the water for injectionsslowly by dripping it down the side of the vial and not directly onto the lyophilized powder. Incline each vial carefully and gently rotate it. Do not invert, vigorously shake, or agitate the vial. The volume, once reconstituted, is 10.5ml with a content of 5mg/ml, and the solution has a transparent, colorless to pale yellow appearance and may contain fine white or translucent fibers. Immediately inspect the reconstituted vials to check if the solution contains particles and if there has been a change in color. Do not use the vial if, upon immediate inspection, you observe any unusual particles other than those described or if the solution changes color. The pH of the reconstituted solution is approximately 6.2.

After reconstitution, it is recommended todilute immediatelythe vials (see below).

• Dilution

By reconstituting as described above, the reconstituted solution in the vial contains 5mg of alglucosidase alfa per ml. The reconstituted volume allows for a precise extraction of 10.0ml (equivalent to 50mg) from each vial. The subsequent dilution of the solution must be performed as follows: extract the reconstituted solution slowly from each vial until the volume for the patient's dose is obtained using a syringe with a needle diameter not exceeding 20 gauge. The recommended final concentration of alglucosidase in the infusion bags ranges from 0.5mg/ml to 4mg/ml. Remove the air contained in the infusion bag. Also remove an equivalent volume of sodium chloride solution containing 9mg/ml (0.9%), which will be replaced with the reconstituted Myozyme. Inject the reconstituted Myozyme slowly into the sodium chloride solution containing 9mg/ml (0.9%). Carefully remove the infusion bag to mix the diluted solution. Do not shake or agitate the infusion bag.

The final infusion solution must be administered immediately after preparation.

The disposal of unused products or packaging will be established in accordance with local requirements.

• Administration

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

The recommended dosing regimen for Myozyme is 20mg/kg of body weight, administered once every 2weeks by intravenous infusion.

The infusion rate of the infusions should be gradually increased. It is recommended that the initial infusion rate be 1mg/kg/hour, and that it be increased gradually by 2mg/kg/hour every 30minutes if no signs of reactions associated with infusion occur until a maximum rate of 7mg/kg/hour is reached.