Naglazyme 1 mg/ml concentrate for solution for infusion

Naglazyme is used to treat patients with MPS VI disease (Mucopolysaccharidosis VI). People with MPS VI disease have either a low level, or no level, of an enzyme called N-acetylgalactosamine 4-sulfatase, which breaks down specific substances (glycosaminoglycans) in the body. As a result, these substances do not get broken down and processed by the body as they should. They accumulate in many tissues in the body, which causes the symptoms of MPS VI.

Naglazyme contains an artificial enzyme called galsulfase. This can replace the natural enzyme which is lacking in MPS VI disease.

Do not use Naglazyme

• If you are allergic (hypersensitive) to galsulfase or any of the other ingredients of Naglazyme.

Take special care with Naglazyme

• If you are treated with Naglazyme, you may develop infusion-associated reactions. An infusion associated reaction is any side effect occurring during the infusion or until the end of the infusion day (see section 4 ?Possible Side Effects?). When you experience such a reaction, you should immediately contact your doctor.
• If you have a fever, or if you are having difficulty breathing, talk with your doctor about delaying your Naglazyme infusion.
• You may have an allergic reaction to the infusion with Naglazyme. If you have an allergic reaction your doctor may slow down, or stop, your infusion. Your doctor may also give you additional medicines to manage any allergic reactions.

Kidney and liver insufficiency

Naglazyme has not been tested in patients with kidney or liver problems. Talk to your doctor if you have kidney or liver insufficiency.

Using other medicines
Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Pregnancy

Naglazyme should not be taken during pregnancy unless clearly necessary. Ask your doctor or pharmacist for advice before taking any medicine.

Breast-feeding

It is not known whether galsulfase is excreted in milk, therefore breast-feeding should be stopped during Naglazyme treatment. Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines
No studies on the effects on the ability to drive and use machines have been performed

Important information about some of the ingredients of Naglazyme

Each 5 ml vial contains 0.8 mmol (18.4 mg) of sodium. To be taken into consideration by patients on a controlled sodium diet.

Your doctor or nurse will administer the product to you.

The concentrate for solution for infusion has to be diluted prior to administration by intravenous infusion.

Dose

The recommended dose regimen is 1 mg/kg body weight administered once every week through a drip into a vein (by intravenous infusion). Each infusion will take approximately 4 hours. For the first hour the infusion rate will be slow (approximately 2.5% of the total solution), with the remaining volume (approximately 97.5%) being taken over the next 3 hours.

If you are given more Naglazyme than you should
Naglazyme is administered under the supervision of a nurse or doctor, he or she will check that the correct dose has been given and act accordingly if necessary.

If you forget to take Naglazyme
If you have missed a Naglazyme infusion, please contact your doctor.

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

Like all medicines, Naglazyme can cause side effects, although not everybody gets them.

The following side effects were reported as being related to Naglazyme:

Very common (affects more than 1 user in 10): Abdominal pain, ear pain, pain, reddened eye, shortness of breath, chills, chest pain, sore throat, stomach pain, poor reflexes, cloudy eyes, swollen face, gastroenteritis, high blood pressure, malaise, nasal congestion, bulging belly button, fever, headache, rash, nausea, vomiting and joint pain.
Common (affects 1 to 10 users in 100): Hives, swelling of the tongue and throat, low blood pressure, difficulty breathing and apnoea.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

Keep out of the reach and sight of children.

Do not take Naglazyme after the expiry date which is stated on the vial after EXP. The expiry date refers to the last day of that month.

Unopened vials:
Store in a refrigerator (2°C - 8°C).

Do not freeze.

Diluted solutions:

Chemical and physical in-use stability has been demonstrated for up to 4 days at room temperature (23°C - 27°C).

From a microbiological safety point of view, the product is to be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and must normally not be longer than 24 hours at 2°C - 8°C followed by up to 24 hours at room temperature (23°C - 27°C) during administration.

Do not take Naglazyme if it contains visible particles.

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

What Naglazyme contains

• The active substance is galsulfase. One ml of Naglazyme contains 1 mg galsulfase. One vial of 5 ml contains 5 mg galsulfase. Galsulfase is recombinant human N-acetylgalactosamine 4-sulfatase produced by genetically engineered Chinese Hamster Ovary (CHO) cells.
• The other ingredients are: sodium chloride, sodium phosphate monobasic, monohydrate, sodium phosphate dibasic, heptahydrate, polysorbate 80, water for injections.

What Naglazyme looks like and contents of the pack

Naglazyme is supplied as a concentrate for solution for infusion. The clear to slightly opalescent and colourless to pale yellow concentrate must be free of visible particles. The solution must be diluted further before it can be infused.

Pack sizes: 1 and 6 vials. Not all package sizes may be marketed.

Marketing Authorization Holder

BioMarin Europe Limited
164 Shaftesbury Avenue
London, WC2H 8HL
United Kingdom

Manufacturer

Catalent UK Packaging Ltd.
Wingates Industrial Park,
Westhoughton, Bolton,
Lancs, BL5 3XX
United Kingdom

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

BelgiëBelgiqueBelgien BioMarin Europe Limited TélTel 00 800 2466 2746 biomarinfrbmrn.com LuxembourgLuxemburg BioMarin Europe Limited TélTel 00 800 2466 2746 biomarinfrbmrn.com

Magyarország BioMarin Europe Limited biomarinhubmrn.com BioMarin Europe Limited Te. 00 359 2 827 23 87 biomarinbgbmrn.com

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Danmark BioMarin Europe Limited Tlf 00 800 2466 2746 biomarindabmrn.com Nederland BioMarin Europe Limited Tel 00 800 2466 2746 biomarinnlbmrn.com

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España BioMarin Europe Limited Tel 00 34 800808508 biomarinesbmrn.com Portugal BioMarin Europe Limited Tel 00 351 21 726 60 53 biomarinptbmrn.com

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Lietuva
BioMarin Europe Limited
biomarinlt@bmrn.com

This leaflet was last approved in

This medicine has been authorised under ?exceptional circumstances?.
This means that because of the rarity of this disease it has been impossible to get complete information on this medicine.
The European Medicines Agency will review any new information on the medicine every year and this leaflet will be updated as necessary.

<------------------------------------------------------------------------------------------------------------------------> The following information is intended for medical or healthcare professionals only:

Naglazyme should not be mixed with other medicinal products in the same infusion, except for those mentioned below.

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

Any unused product or waste material is to be disposed of in accordance with local requirements.

Preparation of the Naglazyme Infusion (Use Aseptic Technique)

The number of vials to be diluted based on the individual patient's weight must be determined and removed from the refrigerator approximately 20 minutes in advance in order to allow them to reach room temperature.

Before dilution, each vial is to be inspected for particulate matter and discolouration. The clear to slightly opalescent and colourless to pale yellow solution must be free of visible particles.

A volume of the sodium chloride 9 mg/ml (0.9%) solution for infusion is to be withdrawn and discarded from a 250 ml infusion bag equal to the total volume of Naglazyme to be added. 100 ml infusion bags should be considered for patients who are susceptible to fluid volume overload and weigh less than 20 kg; in this case the infusion rate (ml/min) should be decreased so that the total duration remains no less than 4 hours. When using 100 ml bags, the volume of Naglazyme may be added directly to the infusion bag.

The volume of Naglazyme is to be slowly added to the sodium chloride 9 mg/ml (0.9%) solution for infusion.

The solution is to be mixed gently for infusion.

The solution is to be visually inspected for particulate matter prior to use. Clear and colourless solutions without visible particles should be used.