ALDURAZYME, 100 U/mL Concentrate for Infusion Solution

2. What you need to know before you receive Aldurazyme

Aldurazyme must not be administered to you

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

Warnings and precautions

Talk to your doctor before you start using 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 can be life-threatening. Symptoms may include respiratory failure (inability of the lungs to function properly), stridor (high-pitched respiratory sound), and other disorders due to airway obstruction, rapid breathing, excessive contraction of the airway muscles causing difficulty breathing (bronchospasm), lack of oxygen in the body tissues (hypoxia), low blood pressure, slow heart rate, or skin rash with itching (urticaria).

• Infusion-related reactions, i.e. any adverse effect that occurs during or up to the end of the day of infusion (see symptoms in section 4 “Possible side effects” below).

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

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

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

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

Using Aldurazyme with other medicines

Tell your doctor if you are using medicines that contain chloroquine or procaine due to the possible risk of reduced action of Aldurazyme.

Tell your doctor or pharmacist if you are using or have recently used any other medicines, including those obtained without a prescription.

Pregnancy, breastfeeding, and fertility

There is not enough experience with the use of Aldurazyme in pregnant women. You should not be given Aldurazyme during pregnancy unless it is absolutely necessary.

It is not known whether Aldurazyme is excreted in breast milk. Breastfeeding should be discontinued during treatment with Aldurazyme.

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

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

No studies have been performed on the ability to drive and use machines.

Aldurazyme contains sodium

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

3. How Aldurazyme is administered

Instructions for use – dilution and administration

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

Administration of Aldurazyme should be carried out in a clinical setting where appropriate resuscitation equipment is available for the management of 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 side effects during an Aldurazyme infusion, the person responsible for the home infusion may stop the infusion and start the appropriate medical treatment.

Dosage

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

Follow your doctor's instructions for administration of this medicine exactly. If you are unsure, consult your doctor again.

If you miss an infusion of Aldurazyme

If you miss an infusion of Aldurazyme, please contact your doctor.

If you are given too much Aldurazyme

If the dose of Aldurazyme administered is too high or the infusion is too rapid, you may experience side effects. Receiving an infusion too quickly may cause nausea, abdominal pain, headache, dizziness, and difficulty breathing (dyspnea). In such situations, the infusion should be stopped or the infusion rate should be decreased immediately. Your doctor will decide whether any additional intervention is required.

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

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 administered the medicine or shortly after (infusion-related reactions). If you experience any reaction like this, you should contact your doctor immediately. The number of these reactions decreased the longer the patients were on treatment with Aldurazyme. Most of these reactions were of mild to moderate intensity. However, a severe allergic reaction (anaphylactic reaction) has been observed in patients during or up to 3 hours after Aldurazyme infusions. Some of the symptoms of this severe allergic reaction were life-threatening and included extreme difficulty breathing, throat swelling, low blood pressure, and low oxygen levels in the body. A few patients who had a history of pre-existing upper airway and pulmonary involvement associated with severe MPS I experienced severe reactions such as bronchospasm (narrowing of the airways), respiratory arrest, and facial swelling. The frequency of bronchospasm and respiratory arrest is not known. The frequency of severe allergic reaction (anaphylactic reaction) and facial swelling is considered common and may affect up to 1 in 10 people.

The very common side effects (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,
• infusion site reaction such as swelling, redness, fluid accumulation, discomfort, itchy skin rash, pale skin color, skin discoloration, or feeling of warmth.

Other side effects include:

Common (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 can be life-threatening if throat swelling blocks the airways
• urticarial rash
• itching
• hair loss
• cold sweat, excessive sweating
• muscle pain
• pallor
• cold hands or feet
• feeling of heat, feeling of cold
• fatigue
• pseudoinfluenza syndrome
• pain at the injection site
• restlessness

Frequency not known (cannot be estimated from the available data)

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

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. You can also report side effects directly through 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. Storage of Aldurazyme

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 is the last day of the month stated.

Unopened vials:

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

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

6. Container contents and additional information

Aldurazyme composition

• The active ingredient is laronidase. One ml of the vial solution contains 100 U of laronidase. Each 5 ml vial contains 500 U of laronidase.
• The other components are sodium chloride, sodium phosphate monobasic monohydrate, sodium phosphate dibasic heptahydrate, polysorbate 80, water for injectable preparations.

Product appearance and container contents

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 box. Only some container sizes may 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

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of last revision of this prospectus:

Other sources of information

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

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

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This information is intended only for healthcare professionals:

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

From a microbiological safety point of view, the product should be used immediately. If not used immediately, the product should not be stored for use if more than 24 hours have passed at a temperature between 2°C - 8°C, assuming the dilution was performed under controlled and validated aseptic conditions.

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

Preparation of Aldurazyme infusion (Use aseptic technique)

• Determine the number of vials to dilute 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 dilution, visually inspect each vial for particles and discoloration. The solution should be transparent to slightly opalescent and colorless to pale yellow, and should not contain visible particles. Do not use vials that show particles or discoloration.
• Determine the total infusion volume based on the individual patient's weight, 100 ml (if body weight is less than or equal to 20 kg) or 250 ml (if body weight is greater than 20 kg) of 0.9% sodium chloride intravenous solution.
• Withdraw and discard from the infusion bag a volume of sodium chloride 9 mg/ml (0.9%) solution equal to the total volume of Aldurazyme to be added.
• Withdraw the required volume from the Aldurazyme vials and combine them.
• Add the resulting Aldurazyme volume to the sodium chloride 9 mg/ml (0.9%) solution for infusion.
• Mix the infusion solution carefully.
• Before use, visually inspect the solution for particles. Only transparent and colorless solutions without visible particles should be used.

The disposal of unused medicinal products and all materials that have come into contact with them should be carried out in accordance with local regulations.