Myozyme 50 mg concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Myozyme 50mg powder for concentrate for solution for infusion

Alglucosidase alfa

Read all of this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as 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 possible side effects not listed in this leaflet. See section 4.

Leaflet contents:

1. What Myozyme is and what it is used for
2. What you need to know before using Myozyme
3. How to use 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 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 regulate glycogen levels (a type of carbohydrate). Glycogen provides energy to the body, but in Pompe disease, glycogen levels can become too high.

Myozyme contains a man-made enzyme called alglucosidase alfa, which can replace the naturally missing enzyme in Pompe disease (acid maltase).

2. What you need to know before using Myozyme

Do not use Myozyme:

If you have experienced potentially life-threatening allergic reactions (hypersensitivity) to alglucosidase alfa or to any of the other components of this medicine (listed in section 6), and if re-administration of the medicine was not successful. Symptoms of potentially life-threatening allergic reactions include, among others, low blood pressure, very rapid heart rate, difficulty breathing, vomiting, facial swelling, hives, or rash.

Warnings and precautions

If you are being treated with Myozyme, you may experience an infusion-associated reaction while the medicine is being administered or in the hours following the infusion. Such a reaction may include various symptoms such as low blood pressure, chest discomfort, throat tightness, facial, lip, or tongue swelling (angioedema), hives, dizziness, rashes, skin itching, nausea, vomiting, cough, and bronchospasm (see section 4 for a complete overview of all infusion-associated reactions). Infusion-associated reactions can sometimes be very serious. If you experience such a reaction, you must inform your doctor immediately. You may require pre-treatment with medications to prevent an allergic reaction (e.g., 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 tract or lung infection. The use of these immunosuppressive medications may further increase this risk.

If you notice severe skin ulcerations, contact your doctor. If you observe swelling of the lower limbs or generalized swelling, contact your doctor. Your doctor should consider interrupting treatment with Myozyme and initiating appropriate medical treatment. Your doctor should evaluate the benefits and risks of resuming treatment with Myozyme.

Using Myozyme with other medicines

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

Pregnancy, breastfeeding, and fertility

Experience with the use of Myozyme in pregnant women is limited. Myozyme should not be used during pregnancy unless clearly necessary. Inform your doctor if you are breastfeeding. Limited data suggest that Myozyme is excreted into human milk in very small amounts. Effects on the breastfed infant are not expected. Therefore, breastfeeding during treatment may be considered. However, as a precautionary measure, you may consult your doctor about temporarily interrupting breastfeeding for the first 24 hours after each dose of Myozyme. If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Driving and using machines

Exercise caution if driving or operating tools or machinery shortly after Myozyme infusion, as you may experience dizziness, somnolence, tremors, and/or low blood pressure.

Myozyme contains sodium

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

3. How to use Myozyme

Myozyme should only be used under the supervision of a physician experienced in the treatment of patients with Pompe disease.

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

Home infusion

Your physician may consider home infusion of Myozyme to be appropriate and safe. If you experience any adverse reaction during a Myozyme infusion, the person administering the home infusion may interrupt 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 through an intravenous drip (intravenous infusion). This medicine is supplied as a powder that must be mixed with sterile water before administration.

If you use more Myozyme than you should

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

• skin and lips turning blue due to lack of oxygen in body tissues, increased heart rate, palpitations
• difficulty breathing, cough
• dizziness, headache, taste disturbance
• high blood pressure, flushing
• swelling of the tongue, vomiting, diarrhea, feeling unwell (nausea)
• chest pain, chest discomfort, throat tightness, fever, chills, feeling cold, redness at the infusion site
• muscle pain
• skin redness

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 interrupted, and corrective treatment may be given as appropriate.

If you forget to use Myozyme

If you miss an infusion, contact your doctor.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Adverse effects have occurred mainly at the time patients were receiving the infusion or shortly afterwards ("infusion-related reactions"). Some of these infusion-related reactions were severe or potentially life-threatening. In some patients, potentially fatal reactions have been observed, such as severe generalized allergic reactions and anaphylactic shock. Symptoms of such reactions include low blood pressure, very rapid heart rate, difficulty breathing, vomiting, swelling of the face, lips, or tongue, hives, or rashes. Some patients have experienced infusion-related adverse effects in the form of flu-like symptoms lasting for a few days after the infusion ended.

If you experience a reaction of this type, inform your doctor immediately. You may require pre-treatment with 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
• Flushing (of the face)
• Fever or elevated body temperature
• Cough
• Increased respiratory rate
• Vomiting
• Low blood oxygen levels

Common: may affect up to 1 in 10 people

• Pallor
• High or increased blood pressure
• Bluish skin discoloration
• Chills
• Agitation
• Tremors
• Headache
• Tingling
• Pain or local reaction at the infusion site
• Dizziness
• Irritability
• Itching of the skin
• Nausea
• Swelling of the face, throat swelling, or severe combined swelling of face, throat, or 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

Frequency not known: cannot be estimated from available data

• Swelling around the eyes
• Asthma
• Abnormal breathing sounds, including wheezing
• Difficulty breathing (including dyspnea)
• Cold extremities (i.e., hands and feet)
• Low or decreased blood pressure
• Constriction of blood vessels causing reduced blood circulation
• Sudden constriction of the bronchi restricting airflow into and out of the lungs (bronchospasm)
• Feeling of warmth
• Feeling of cold
• General feeling of discomfort (malaise)
• Feeling of weakness
• Somnolence
• Fainting
• Burning sensation
• Increased sweating
• Tearing
• Mottled skin
• Restlessness
• Wheezing
• Throat irritation
• Lack of oxygen in body tissues
• Decreased heart rate
• Cardiac arrest
• Strong heartbeats that may be rapid or irregular (palpitations)
• Chest pain (not cardiac)
• Inflammation of the membrane lining the eyeball and eyelid
• Abdominal pain
• Indigestion
• Difficulty swallowing
• Joint pain
• Temporary cessation or sudden interruption 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 the infusion site in case of drug extravasation outside blood vessels
• Redness of the palms
• Transient skin discoloration
• Redness at the infusion site
• Hives (rash) at the infusion site
• Itching at the infusion site
• Blister

Reporting of adverse effects

If you experience any adverse effects, talk to your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Myozyme

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

Do not use this medicine after the expiry date stated on the label after "EXP". The expiry date is the last day of the month indicated.

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

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

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Myozyme

• 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 ranges from 0.5 mg to 4 mg/ml.

• The other components are:

• mannitol (E421)

• sodium dihydrogen phosphate monohydrate (E339)

• disodium phosphate heptahydrate (E339)

• polysorbate 80 (E433).

Appearance of Myozyme 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. Only certain pack sizes may be marketed.

The powder is white or almost 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 more information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

Date of the most recent review of this leaflet:

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu. There are also links to other websites about rare diseases and orphan medicines.

This information is intended for healthcare professionals only:

Instructions for use – reconstitution, dilution, and administration

Myozyme must be reconstituted with water for injections and subsequently diluted with a sodium chloride solution for injection containing 9 mg/ml (0.9%) for intravenous infusion. Reconstitution and dilution must be performed in accordance with good manufacturing practice, particularly with regard to aseptic technique.

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

Calculate the number of vials required for reconstitution based on the patient's dosing regimen (mg/kg) and 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.

Use aseptic technique

• Reconstitution

Reconstitute each 50 mg Myozyme vial with 10.3 ml of water for injections using a syringe with a needle gauge no larger than 20. Add the water for injections slowly by dripping down the side of the vial, not directly onto the lyophilized powder. Gently tilt each vial and swirl gently. Do not invert, shake vigorously, or agitate the vial. After reconstitution, the volume is 10.5 ml with a concentration of 5 mg/ml. The solution is transparent, colourless to pale yellow, and may contain fine thread-like white particles or translucent fibres. Immediately inspect reconstituted vials for particulate matter and discoloration. Do not use the vial if, upon immediate inspection, foreign particles other than those described above are observed or if the solution has changed colour. The pH of the reconstituted solution is approximately 6.2.

After reconstitution, immediate dilution of the vials is recommended (see below).

• Dilution

Following reconstitution as described above, the reconstituted solution in the vial contains 5 mg of alglucosidase alfa per ml. The reconstituted volume allows accurate withdrawal of 10.0 ml (equivalent to 50 mg) from each vial. Further dilution of the solution should be performed as follows: slowly withdraw the reconstituted solution from each vial using a syringe with a needle gauge no larger than 20, until the volume required for the patient's dose is obtained. The recommended final concentration of alglucosidase alfa in infusion bags ranges between 0.5 mg/ml and 4 mg/ml. Remove air from the infusion bag. Also remove an equivalent volume of 9 mg/ml (0.9%) sodium chloride solution for injection, which will be replaced with the reconstituted Myozyme. Slowly inject the reconstituted Myozyme directly into the 9 mg/ml (0.9%) sodium chloride solution for injection. Gently swirl the infusion bag to mix the diluted solution. Do not shake or agitate the infusion bag.

The final infusion solution should be administered immediately after preparation.

Disposal of unused products or containers must comply with local requirements.

• Administration

Administration of the diluted solution is recommended to begin within three hours. The total time between reconstitution and completion of the infusion must not exceed 24 hours.

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

The infusion rate should be progressively increased. The initial infusion rate should be 1 mg/kg/hour, gradually increasing by 2 mg/kg/hour every 30 minutes if no signs of infusion-associated reactions occur, up to a maximum rate of 7 mg/kg/hour.