Myozyme

Patient Information Leaflet

Myozyme 50 mg powder for concentrate for solution for infusion

Alglucosidase alfa
Please read all of this leaflet carefully before you start 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, pharmacist or nurse.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

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

1. What Myozyme is and what it is used for

Myozyme is used to treat adults, children, and adolescents of any age who have a confirmed diagnosis of Pompe disease.
People affected by Pompe disease have reduced levels of an enzyme called alpha-glucosidase. This enzyme helps the body regulate glycogen levels (a type of carbohydrate). Glycogen provides energy to the body, but in Pompe disease, glycogen can accumulate to abnormally high levels.
Myozyme contains a recombinant human enzyme called alglucosidase alfa, which replaces the naturally deficient enzyme in Pompe disease.

2. What you should know before taking Myozyme

Do not use Myozyme
If you have previously experienced life-threatening allergic reactions (hypersensitivity) to alglucosidase alfa or to any of the other ingredients of this medicine (listed in section 6), and if re-administration of the medicine has not proven effective. Symptoms of life-threatening allergic reactions include, among others, hypotension, very rapid heart rate, breathing difficulties, vomiting, facial swelling, hives or skin rash.

Warnings and precautions
When being treated with Myozyme, you may experience an infusion-associated reaction during or within hours after the infusion. This reaction may present with various symptoms such as hypotension, chest discomfort, throat tightness, swelling of the face, lips, or tongue (angioedema), hives, dizziness, skin rash, itching, nausea, vomiting, cough, and bronchospasm (see section 4 for a complete overview of all infusion-associated reactions). In some cases, an infusion-associated reaction may be severe. If you experience such a reaction, contact your doctor immediately. You may need to receive medications prior to treatment to prevent an allergic reaction (such as antihistamines and/or corticosteroids) or to reduce fever (antipyretics).

In clinical studies, physicians have used medications to suppress the immune system and reduce antibody production. Since you have Pompe disease, you are at risk of developing a serious respiratory or lung infection. The use of these immunosuppressive medications may further increase this risk.

If you notice severe ulcerative skin lesions, inform your doctor. If you experience swelling in your lower limbs or generalized swelling, inform your doctor. Your doctor should consider interrupting Myozyme administration and initiating appropriate medical treatment. Your doctor should carefully evaluate the risks and benefits of re-administering Myozyme.

Other medicines and Myozyme
Inform your doctor or pharmacist if you are currently using, have recently used, or might use any other medicines.

Pregnancy, breastfeeding, and fertility
Experience with the use of Myozyme in pregnant women is limited. Myozyme should not be administered during pregnancy unless clearly necessary. Inform your doctor if you are breastfeeding. Limited data suggest that Myozyme passes into breast milk in very small amounts. Effects in breastfed infants are not expected. Therefore, breastfeeding during treatment may be considered. However, you may discuss with your doctor whether to interrupt breastfeeding as a precautionary measure for the first 24 hours after each dose of Myozyme. If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Driving and using machines
Do not drive or operate tools or machinery immediately after Myozyme infusion, as dizziness, drowsiness, tremor, and/or low blood pressure may occur.

Myozyme contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per vial, i.e., it is practically "sodium-free".

3. How to take Myozyme

Myozyme must be administered exclusively under the supervision of a physician experienced in the treatment of Pompe disease.
The administered dose is based on body weight. The recommended dose of Myozyme is 20 mg/kg of body weight, administered once every 2 weeks.

Home infusion
Your doctor may consider home infusion of Myozyme appropriate for you if it is safe and convenient. If you experience side effects during a Myozyme infusion, the home infusion personnel may stop the infusion and initiate 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 by intravenous infusion (a drip into a vein). It is supplied as a powder that must be mixed with sterile water before administration.

If you take more Myozyme than you should
If Myozyme is administered at a higher dose or at a faster infusion rate than recommended, you may experience infusion-associated reactions. Such reactions may include symptoms such as:

• bluish skin and lips due to lack of oxygen in body tissues, increased heart rate, palpitations
• breathing difficulties, cough
• dizziness, headache, taste disturbances
• high blood pressure, hot flushes
• tongue swelling, vomiting, diarrhea, nausea
• chest pain, chest discomfort, throat tightness, fever, chills, feeling cold, redness at the infusion site
• muscle pain
• skin redness

If you experience any such reaction, inform your doctor immediately (see section 2). The infusion rate will be reduced or the infusion stopped, and, depending on the situation, you may receive corrective treatment.

If you forget to take Myozyme
If an infusion is missed, consult your doctor.

If you have any questions about 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.
In patients, side effects occurred mainly during or shortly after administration ("infusion-related reactions"). Some of the infusion-related side effects were serious or potentially fatal. Life-threatening reactions, including severe generalized allergic reactions and anaphylactic shock, have been reported in some patients. Symptoms of such reactions include low blood pressure, very rapid heartbeat, breathing difficulties, vomiting, swelling of the face, lips or tongue, hives or skin rash. Some patients experienced infusion-related side effects in the form of flu-like symptoms, which lasted for several days after completion of the infusion.
If you notice any of these types of side effects, contact your doctor immediately. You may need to receive medications before treatment to prevent an allergic reaction (such as antihistamines and/or corticosteroids) or to reduce fever (antipyretics).

Very common: may affect more than 1 in 10 people

• Hives
• Skin rash
• Increased heart rate
• Flushing (of the face)
• Fever or increased body temperature
• Cough
• Rapid breathing
• Vomiting
• Low blood oxygen levels

Common: may affect up to 1 in 10 people

• Pallor
• Increased blood pressure/hypertension
• Bluish skin discoloration
• Chills
• Agitation
• Tremor
• Headache
• Tingling
• Pain or local reaction at the infusion site
• Dizziness
• Irritability
• Itching
• Nausea and urge to vomit
• Swelling of the face, throat swelling, or severe swelling involving face, throat and tongue due to a severe allergic reaction
• Swelling of arms and legs
• Nausea
• Chest discomfort
• Throat tightness
• Diarrhea
• Fatigue
• Muscle pain
• Muscle spasms
• Severe skin ulcerative lesions
• Skin redness

Not known: (frequency cannot be estimated from the available data)

• Swelling around the eyes
• Asthma
• Abnormal breathing sounds, including wheezing
• Breathing difficulties (including shortness of breath)
• Cold extremities (hands, feet)
• Hypotension (reduced or low blood pressure)
• Constriction of blood vessels leading to reduced blood flow
• Sudden constriction of the bronchi, resulting in reduced airflow (bronchospasm)
• Feeling of warmth
• Feeling of cold
• General feeling of illness (malaise)
• Feeling of weakness
• Drowsiness
• Fainting
• Burning sensation
• Increased sweating
• Watery eyes
• Skin patches
• Restlessness
• Wheezing
• Throat irritation
• Lack of oxygen in body tissues
• Decreased heart rate
• Cardiac arrest
• Strong heartbeat that may be rapid or irregular (palpitations)
• Chest pain (non-cardiac)
• Inflammation of the membrane covering the eyes or eyelids
• Abdominal pain
• Indigestion
• Difficulty swallowing
• Joint pain
• Temporary interruption or sudden cessation of breathing
• Proteinuria
• Nephrotic syndrome: swelling of lower limbs, generalized edema and proteinuria
• Swelling and thickening of the skin at the infusion site in case of extravasation (leakage of the product outside blood vessels)
• Redness of the palms
• Transient change in skin color
• Redness at the infusion site
• Hives (rash) at the infusion site
• Itching at the infusion site
• Blisters

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly through the national reporting system mentioned in Annex 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, immediate use of the product is recommended. However, chemical and physical stability has been demonstrated for 24 hours at 2 °C – 8 °C, provided the medicine is protected from light.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer require. This will help protect the environment.

6. Package Contents 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; following dilution, the concentration ranges between 0.5 mg and 4 mg/mL.
• The excipients are:
  • mannitol (E421)
  • monosodium phosphate monohydrate (E339)
  • disodium phosphate heptahydrate (E339)
  • polysorbate 80 (E433)

Description of the Appearance of Myozyme and Contents of the Package
Myozyme is a powder for concentrate for solution for infusion in a vial (50 mg/vial).
Each package contains 1, 10, or 25 vials. Not all pack sizes may be marketed.
The powder is white to off-white. After reconstitution, the solution is clear, colourless to pale yellow, and may contain 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 on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

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

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

България (Bulgaria)
Swixx Biopharma EOOD
Тел.: +359 (0)2 4942 480

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

Česká republika (Czech Republic)
Sanofi s.r.o.
Tel: +420 233086 111

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

Danmark (Denmark)
Sanofi A/S
Tlf: +45 45 16 70 00

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

Deutschland (Germany)
Sanofi-Aventis Deutschland GmbH
Tel.: 0800 04 36 996
Tel. from abroad: +49 69 305 70 13

Österreich (Austria)
sanofi-aventis GmbH
Tel: +43 1 80 185 – 0

Eesti (Estonia)
Swixx Biopharma OÜ
Tel: +372 640 10 30

Polska (Poland)
Sanofi Sp. z o.o.
Tel.: +48 22 280 00 00

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

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

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

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

France
Sanofi Winthrop Industrie
Tél: 0 800 222 555
Call from abroad: +33 1 57 63 23 23

Slovenija (Slovenia)
Swixx Biopharma d.o.o.
Tel: +386 1 235 51 00

Hrvatska (Croatia)
Swixx Biopharma d.o.o.
Tel: +385 1 2078 500

Slovenská republika (Slovakia)
Swixx Biopharma s.r.o.
Tel: +421 2 208 33 600

Ireland
Sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +353 (0)1 4035600

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

Ísland (Iceland)
Vistor hf.
Sími: +354 535 7000

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

Italia (Italy)
Sanofi S.r.l.
Tel: 800536389

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

Latvija (Latvia)
Swixx Biopharma SIA
Tel: +371 6 616 47 50

Κύπρος (Cyprus)
C.A. Papaellinas Ltd.
Τηλ: +357 22 741741

Lietuva (Lithuania)
Swixx Biopharma UAB
Tel: +370 5 236 91 40

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 therapeutic treatments are provided.
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The following information is intended exclusively for healthcare professionals:

Instructions for Use – Reconstitution, Dilution, and Administration
Myozyme must be reconstituted with water for injections, then diluted with an injectable solution of 9 mg/mL (0.9%) sodium chloride, and administered via intravenous infusion. Reconstitution and dilution must be performed under aseptic conditions in accordance with good practice, particularly with regard to sterility.

Due to the protein nature of the product, particles may form in the reconstituted solution and in the final infusion bags. Therefore, use a low-protein-binding 0.2-micron in-line filter for administration. The use of a 0.2-micron in-line filter has been shown to remove visible particles without causing apparent loss of protein or activity.

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

Follow aseptic technique

Reconstitution

• Reconstitute each 50 mg vial of Myozyme with 10.3 mL of water for injections using a syringe with a needle of less than 20 gauge diameter. Add the water for injections slowly, drop by drop, along the wall of the vial, not directly onto the solid lyophilized medicine. Then gently tilt and rotate each vial without inverting it, and avoid rapid rotation or shaking. The reconstituted volume is 10.5 mL, containing 5 mg of enzyme per mL, appearing as a clear, colourless to pale yellow solution, which may contain particles in the form of fine white filaments or translucent fibres. Immediately inspect reconstituted vials for particulate matter and discoloration. If inspection reveals foreign particles other than those described above, or if the solution is discoloured, do not use the product. The pH of the reconstituted solution is approximately 6.2.
• After reconstitution, prompt dilution of the vials is recommended (see below).

Dilution

• If reconstituted according to the procedure described above, the solution within the vial will contain 5 mg of alglucosidase alfa per mL. The reconstituted volume allows accurate aspiration of 10.0 mL (equivalent to 50 mg) from each vial. Subsequently, further dilute as follows: slowly withdraw the reconstituted solution from each vial using a syringe with a needle of less than 20 gauge diameter, until the total volume corresponds to the patient’s dose. The recommended final concentration of alglucosidase alfa in the infusion bag should be between 0.5 mg/mL and 4 mg/mL. Remove air from the infusion bags and withdraw an equivalent volume of 9 mg/mL (0.9%) sodium chloride injectable solution to be replaced with the reconstituted Myozyme. Slowly inject the reconstituted Myozyme directly into the 9 mg/mL (0.9%) sodium chloride injectable solution. Gently invert and roll the infusion bag to mix the diluted solution. Do not shake or vigorously agitate the infusion bag.
• Administer the final infusion solution as soon as possible.
• Unused product and waste material must be disposed of in accordance with local legal requirements.

Administration
It is recommended to begin administering the diluted solution within three hours. The total time from reconstitution to the end of infusion must not exceed 24 hours.

The recommended dosage of Myozyme is 20 mg/kg body weight, administered once every two weeks as an intravenous infusion.

Administer infusions incrementally. A starting infusion rate of 1 mg/kg/hour is recommended, with gradual increases of 2 mg/kg/hour every 30 minutes in the absence of infusion-associated reactions, up to a maximum rate of 7 mg/kg/hour.