Prospecto: information for the user

Aldurazyme, 100U/ml concentrated solution for infusion

Laronidase

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

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medication has been prescribed only for you and should not be given to other peopleeven if they have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospect. See section 4.

Content ofthe prospect:

1.What is Aldurazyme and for what it is used

2.What you need to know before receiving Aldurazyme

3.How to administer Aldurazyme

4.Possible adverse effects

5.Storage of Aldurazyme

6.Contents of the package and additional information

Aldurazyme is used to treat patients with MPSI (mucopolisacaridosisI). It is administered to treat the non-neurological manifestations of the disease.

People with MPSI have a low level or lack of the enzyme called?-L-iduronidase that breaks down specific substances (glucosaminoglycans) in the body. As a result, these substances are not broken down or processed by the body as they should. They accumulate in many tissues of the body, causing the symptoms ofMPSI.

Aldurazyme is an artificial enzyme called laronidase, which can replace the missing natural enzyme in MPSI.

You should not receive Aldurazyme

If you are allergic (hypersensitive) to laronidase or to any of the other components of this medication (listed in section 6).

Warnings and precautions

Consult your doctor before starting to use Aldurazyme.

Contact your doctor immediately if treatment with Aldurazyme causes:

• Allergic reactions, including anaphylaxis (a severe allergic reaction) - see section 4 “Possible side effects”. Some of these reactions may be life-threatening. Symptoms may include respiratory distress (difficulty breathing), stridor (high-pitched breathing sound) and other disorders due to airway obstruction, rapid breathing, excessive contraction of airway muscles causing difficulty breathing (bronchospasm), tissue hypoxia, low blood pressure, slow heart rate, or skin rash with itching (urticaria).

• Reactions associated with infusion, that is, any adverse effect that occurs during or up to the end of the infusion day (see symptoms in section 4 “Possible side effects” below).

If these reactions occur, the administration of Aldurazyme should be stopped immediately and your doctor will initiate appropriate medical treatment.

These reactions may be especially severe if you have a pre-existing airway obstruction (difficulty breathing) associated with MPS I.I.

You may be administered additional medications to help prevent allergic-type reactions, such as antihistamines, fever-reducing medications (e.g. paracetamol), and/or corticosteroids.

Your doctor will also decide if you can continue receiving Aldurazyme.

Use of Aldurazyme with other medications

Inform your doctor if you are using medications containing chloroquine or procaine due to the possible risk of decreased Aldurazyme action.

Inform your doctor or pharmacist if you are using or have recently used any other medication, including those acquired without a prescription.

Pregnancy, breastfeeding, and fertility

There is insufficient experience with the use of Aldurazyme in pregnant women. Aldurazyme should not be administered during pregnancy unless absolutely necessary.

The excretion of Aldurazyme in breast milk is unknown. It is recommended to discontinue breastfeeding during treatment with Aldurazyme.

There is no available information about the effects of Aldurazyme on fertility.

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

No studies have been conducted on the ability to drive and operate machines.

Aldurazyme contains sodium

This medication contains 30 mg of sodium (main component of table salt/for cooking) per vial. This is equivalent to 1.5% of the maximum daily sodium intake recommended for an adult.

Instructions for Use – Dilution and Administration

The concentrate for infusion solution must be diluted before administration and is for intravenous use (see information for healthcare professionals).

Aldurazyme administration should be carried out in a suitable clinical setting where there is access to appropriate resuscitation equipment for managing medical emergencies.

Home Infusion

Your doctor may consider that you can receive home infusion of Aldurazyme if it is safe and convenient to do so.If you experience any adverse effects during an Aldurazyme infusion, the home infusion administrator may interrupt the infusion and initiate appropriate medical treatment.

Dosage

The recommended dosage regimen for Aldurazyme is 100 U/kg of body weight, administered once a week via intravenous infusion.The initial infusion rate of 2 U/kg/h may be increased gradually every 15 minutes, if tolerated, up to a maximum of 43 U/kg/h.The total volume of administration should be administered in approximately 3-4 hours.

Follow exactly the administration instructions for this medication as indicated by your doctor. If in doubt, consult your doctor again.

If You Forget to Receive an Aldurazyme Infusion

If you forget to receive an Aldurazyme infusion, please contact your doctor.

If You Receive More Aldurazyme Than You Should

If the administered dose of Aldurazyme is too high or the infusion is too rapid, adverse reactions to the medication may occur.Receiving an infusion of Aldurazyme too quickly may cause nausea, abdominal pain, headache, dizziness, and difficulty breathing (dyspnea).In such situations, the infusion should be interrupted or the infusion rate should be decreased immediately.Your doctor will decide if additional intervention is required.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.Side effects were mainly observed while the patients were receiving the medicine or shortly after (reactions associated with infusion). If you experience any reaction like this, you mustcontact your doctor immediately.The number of these reactions decreased as the patients were on longer treatment with Aldurazyme. Most of these reactions were of mild to moderate intensity. However, a severe systemic allergic reaction (anaphylactic reaction) has been observed in patients during or up to 3 hours after Aldurazyme infusions. Some of the symptoms of that severe allergic reaction posed a life-threatening risk and included extreme difficulty breathing, throat swelling, low blood pressure, and low oxygen levels in the body. A few patients with a prior history of upper respiratory tract and lung involvement associated with MPS I severe experienced severe reactions such as bronchospasm (narrowing of the airways), respiratory arrest, and facial swelling. The frequency of bronchospasm and respiratory arrest is unknown. The frequency of the severe allergic reaction (anaphylactic reaction) and facial swelling is considered frequent and may affect up to 1 in 10 people.

The very common symptoms (may affect more than 1 in 10 people) that were not severe include:

• headache,
• nausea,
• abdominal pain,
• skin rash,
• joint disease,
• joint pain,
• back pain,
• pain in arms or legs,
• redness,
• fever, chills,
• increased heart rate,
• increased blood pressure,
• reactionat the infusion site such as swelling, redness, fluid accumulation, discomfort, skin rash with itching, pale skin color, skin discoloration, or sensation of heat.

Other side effects include the following::

Frequent (may affect up to 1 in 10 people)

• increased body temperature
• tingling
• dizziness
• cough
• difficulty breathing
• vomiting
• diarrhea
• rapid swelling under the skin in areas such as the face, throat, arms, and legs, which may pose a life-threatening risk if the throat swelling blocks the airways
• urticarial hives
• itching
• hair loss
• excessive sweating, cold sweat
• muscle pain
• pale skin
• cold hands or feet
• sensation of heat, sensation of cold
• fatigue
• influenza-like syndrome
• pain at the injection site
• restlessness

Frequency unknown (cannot be estimated from available data)

• allergic reactions (hypersensitivity)
• abnormally slow heart rate
• high or abnormally high blood pressure
• throat swelling
• blue skin color (due to low oxygen levels in the blood)
• rapid breathing
• skin redness
• distribution of the medicine to the surrounding tissue at the injection site, where it may cause damage
• lung failure to function properly (respiratory insufficiency)
• throat swelling
• high-pitched respiratory sound
• obstruction of the airways that causes difficulty breathing
• swelling of the lips
• swelling of the tongue
• swelling especially of the ankles and feet due to fluid retention
• specific antibody to the medicine, a protein in the blood produced in response to the medicine
• antibody that neutralizes the effect of the medicine

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet.You can also report them directly through thenational notification system included in theAppendixV.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.

Unopened vials:

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

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Aldurazyme

• The active ingredient is laronidase. One mL of the solution in the vial contains 100 U of laronidase. Each vial of 5 mL contains 500 U of laronidase.
• The other components are sodium chloride, monobasic monohydrate sodium phosphate, heptahydrate dibasic sodium phosphate, polisorbate 80, and water for injection.

Appearance of the product and contents of the container

Aldurazyme is presented as a concentrate for solution for infusion. It is a transparent to slightly opalescent and colorless to pale yellow solution.

Container sizes: 1, 10, and 25 vials per carton. Some container sizes may only be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Sanofi B.V.,Paasheuvelweg 25, 1105 BP Amsterdam,Netherlands.

Manufacturer

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

For more information about this medicinal product, please contact the local representative of the marketing authorization holder:

Last update of this leaflet:

Other sources of information

The detailed information on this medicinal product is available on the website of the European Medicines Agencyhttp://www.ema.europa.eu. It also provides links to other websites on rare diseases and orphan medicinal products.

The website of the European Medicines Agency can be found in all languages of the European Union/European Economic Area.

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This information is intended for healthcare professionals only:

Each vial of Aldurazyme is intended for single use. The concentrate for solution for infusion must be diluted withsodium chloride 9 mg/mL (0.9%) solution for infusionusing aseptic technique. It is recommended that the Aldurazyme solution diluted be administered to patients using an infusion device equipped with a 0.2µm filter.

From a microbiological point of view, the product should be used immediately. If not used immediately, the product should be stored at 2?°C- 8?C and the dilution should have been prepared in controlled and validated aseptic conditions.

Aldurazyme should not be mixed with other medicinal products in the same infusion.

Preparation of the Aldurazyme infusion (Use aseptic technique)

• Determine the number of vials to be diluted based on the individual patient's weight. Remove the required vials from the refrigerator approximately 20 minutes before to allow them to reach room temperature (below 30°C).
• Before diluting, visually inspect each vial for particles and discoloration. The transparent to slightly opalescent and colorless to pale yellow solution, should not have visible particles. Do not use vials that show particles or discoloration.
• Determine the total infusion volume based on the individual patient's weight, 100ml (if the body weight is less than or equal to20kg) or 250ml (if the body weight is greater than20kg) of sodium chloride 9 mg/mL (0.9%) solution for infusion.
• Remove and discard from the infusion bag a volume of sodium chloride 9 mg/mL (0.9%) solution for infusion equal to the total volume of Aldurazyme to be added.
• Remove the required volume of Aldurazyme from the vials and combine them.
• Add the resulting volume of Aldurazyme to the sodium chloride 9 mg/mL (0.9%) solution for infusion.
• Mix the infusion solution carefully.
• Before use, visually inspect the infusion solution for particles. Only solutions that are transparent and colorless without visible particles should be used.

The disposal of unused medicinal product and all materials that have been in contact with it, should be in accordance with local regulations.