Aldurazyme, 100 U/ml concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Aldurazyme, 100 U/ml concentrate for solution for infusion

Laronidase

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 or pharmacist.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you. It may harm them.
• If you experience any adverse reactions, talk to your doctor or pharmacist, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of this leaflet:

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

1. What Aldurazyme is and what it is used for

Aldurazyme is used for the treatment of patients with MPS I disease (mucopolysaccharidosis I). It is administered to treat the non-neurological manifestations of the disease.

Patients with MPS I disease have low or no levels of an enzyme called α-L-iduronidase, which breaks down specific substances (glycosaminoglycans) in the body. As a result, these substances are not broken down or processed by the body as they should be. They accumulate in many body tissues, causing the symptoms of MPS I.

Aldurazyme is a recombinant human enzyme known as laronidase, which can replace the naturally missing enzyme in MPS I disease.

2. What you need to know before receiving Aldurazyme

Do not use Aldurazyme

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

Warnings and precautions

Talk to your doctor before starting treatment with 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 failure/breathing difficulty (inability of the lungs to function properly), stridor (high-pitched breathing sound), and other disorders due to airway obstruction, rapid breathing, excessive contraction of the airway muscles causing breathing difficulty (bronchospasm), lack of oxygen in body tissues (hypoxia), low blood pressure, slow heart rate, or itchy skin rash (urticaria).

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

If these reactions occur, administration of Aldurazyme must be stopped immediately and your doctor will start appropriate medical treatment.

These reactions may 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-type reactions, such as antihistamines, fever-reducing medicines (e.g. paracetamol) and/or corticosteroids.

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

Use of Aldurazyme with other medicines

Tell your doctor if you are taking medicines containing chloroquine or procaine, due to the possible risk of reduced effect of Aldurazyme.

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

Pregnancy, breast-feeding and fertility

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

It is unknown whether Aldurazyme is excreted in human breast milk. Breast-feeding is recommended to be discontinued during treatment with Aldurazyme.

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

If you are pregnant or breast-feeding, 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 on the ability to drive and use machines have been performed.

Aldurazyme contains sodium

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

3. How Aldurazyme is administered

Instructions for use – dilution and administration

The concentrate for solution for infusion must be diluted prior to administration and is for intravenous use only (see information for physicians or healthcare professionals).

Administration of Aldurazyme should be performed in an appropriate clinical setting where adequate resuscitation equipment is available for the management of medical emergencies.

Home infusion

Your physician may consider that you can receive home infusion of Aldurazyme if it is safe and appropriate to do so. If you experience any adverse reactions during an Aldurazyme infusion, the person administering the home infusion may stop the infusion and initiate appropriate medical treatment.

Dosage

The recommended dosage regimen of Aldurazyme is 100 U/kg body weight, administered once weekly via 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 infused over approximately 3–4 hours.

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

If you missed an Aldurazyme infusion

If you missed an Aldurazyme infusion, please contact your physician.

If you are given more Aldurazyme than you should have

If the administered dose of Aldurazyme is too high or the infusion is too fast, adverse drug reactions may occur. Receiving an infusion of Aldurazyme too rapidly may cause nausea, abdominal pain, headache, dizziness, and difficulty breathing (dyspnea). In such situations, the infusion should be stopped or the infusion rate reduced immediately. Your physician will decide whether additional intervention is required.

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

4. Possible adverse effects

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

Adverse effects were observed mainly while patients were receiving the infusion or shortly afterwards (infusion-associated reactions). If you experience any such reaction, you must contact your doctor immediately. The number of these reactions decreased the longer patients remained on treatment with Aldurazyme. Most of these reactions were mild to moderate in 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 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 with prior history of upper airway and pulmonary involvement associated with severe MPS I experienced serious 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 severe allergic reaction (anaphylactic reaction) and facial swelling is considered frequent and may affect up to 1 in 10 people.

Very common adverse effects (may affect more than 1 in 10 people), which were not serious, include:

• headache,
• nausea,
• abdominal pain,
• rash,
• joint disease,
• joint pain,
• back pain,
• pain in arms or legs,
• flushing,
• fever, chills,
• increased heart rate,
• increased blood pressure,
• infusion site reaction such as swelling, redness, fluid accumulation, discomfort, itchy rash, pale skin colour, skin discolouration, or sensation of warmth.

Other adverse effects include the following:

Common (may affect up to 1 in 10 people)

• increased body temperature
• tingling
• dizziness
• cough
• difficulty breathing
• vomiting
• diarrhoea
• rapid swelling beneath the skin in areas such as the face, throat, arms, and legs, which can be life-threatening if throat swelling blocks the airways
• urticaria (hives)
• itching
• hair loss
• cold sweat, excessive sweating
• muscle pain
• paleness
• cold hands or feet
• sensation of warmth, sensation of cold
• fatigue
• influenza-like syndrome
• injection site pain
• restlessness

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

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

Reporting of adverse effects

If you experience any type of adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse 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 stated on the label after EXP. The expiry date is the last day of the month indicated.

Unopened vials:

Store in a refrigerator (between 2 ºC and 8 ºC).

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 Aldurazyme

• The active substance 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, monobasic monohydrate sodium phosphate, dibasic heptahydrate sodium phosphate, polysorbate 80, water for injections.

Appearance of the product and contents of the pack

Aldurazyme is presented as a concentrate for solution for infusion. It is a solution ranging from clear to slightly opalescent and from colourless to pale yellow.

Pack sizes: 1, 10 and 25 vials per carton. Only certain pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

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

Manufacturer

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

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

Date of the most recent review of this leaflet:

Other sources of information

Detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu. This site also provides links to other websites on rare diseases and orphan medicinal products.

This leaflet is available in all languages of the European Union/European Economic Area on the European Medicines Agency website.

This information is intended for healthcare professionals only:

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

From a microbiological standpoint, the product should be used immediately. If not used immediately, the product should not be stored for longer than 24 hours at a temperature between 2°C and 8°C, provided that dilution has been carried out under controlled and validated aseptic conditions.

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

Preparation of Aldurazyme Infusion (Use an aseptic technique)

• Determine the number of vials to be diluted based on the individual patient's body weight. Remove the required number of vials from the refrigerator approximately 20 minutes before use to allow them to reach room temperature (below 30°C).
• Before dilution, visually inspect each vial for particles and discoloration. The solution, which ranges from clear to slightly opalescent and colorless to pale yellow, must not contain visible particles. Do not use vials showing particles or discoloration.
• Determine the total infusion volume based on the patient's individual body weight: 100 ml (if body weight is ≤20 kg) or 250 ml (if body weight is >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 total volume of Aldurazyme to the sodium chloride 9 mg/ml (0.9%) infusion solution.
• Gently mix the infusion solution.
• Before use, visually inspect the solution for particles. Only clear, colorless solutions without visible particles should be used.

Any unused medicinal product and materials that have come into contact with it must be disposed of in accordance with local regulations.