Naglazyme

PACKAGE LEAFLET: INFORMATION FOR THE USER

Naglazyme 1 mg/ml concentrate for solution for infusion

Galsulfase
Please read this leaflet carefully before using this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• If any of the side effects worsens, or if you notice any side effects not listed in this leaflet, inform your doctor.

Contents of this leaflet:

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

1. What this medicine is and what it is used for

Naglazyme is used to treat patients with MPS VI (Mucopolysaccharidosis VI).
People affected by MPS VI have a deficiency, or complete absence, of an enzyme called
N-acetylgalactosamine 4-sulfatase, which is responsible for breaking down specific substances
(glycosaminoglycans) present in the body. As a result, these substances are not broken down by the body as they should be, but instead accumulate in many tissues, causing the symptoms of MPS VI.
How this medicine works
This medicine contains a recombinant enzyme called galsulfase, which is able to replace the naturally missing enzyme in patients with MPS VI. Treatment with this medicine has been shown to improve the ability to walk and to climb stairs, as well as to reduce the levels of glycosaminoglycans in the body. This medicine may improve the symptoms of MPS VI.

2. What you should know before this medicine is administered to you

Do not receive this medicine:

• If you have experienced severe or potentially life-threatening allergic reactions (hypersensitivity) to galsulfase or to any of the excipients in Naglazyme, and re-administration of the medicine did not achieve the desired outcome.

Warnings and precautions

• If you are being treated with Naglazyme, you may develop infusion-related reactions. An infusion-related reaction is an adverse effect that occurs during or on the day of infusion (see section 4 “Possible side effects”). If such a reaction occurs, contact your doctor immediately.
• If you experience an allergic reaction, your doctor may slow down or stop the infusion. Your doctor may also start you on appropriate medical treatment to manage allergic reactions.
• If you have fever or difficulty breathing, consult your doctor before receiving this medicine about the possibility of delaying the Naglazyme infusion.
• If you have pre-existing heart disease, inform your doctor at any time during treatment with Naglazyme. Your doctor may adjust the infusion based on this information.
• This medicine has not been studied in patients with liver or kidney problems. Contact your doctor if you have renal or hepatic impairment.
• Inform your doctor if you experience muscle pain, numbness in the arms or legs, or intestinal or bladder problems, as these may be caused by pressure on the spinal cord.

Other medicines and Naglazyme
Inform your doctor or pharmacist if you are taking or have recently taken any other medicines, including those not requiring a prescription.
Pregnancy and breastfeeding
Naglazyme must not be administered during pregnancy unless clearly necessary.
Consult your doctor or pharmacist before taking any medicine. It is not known whether galsulfase is excreted in human milk; therefore, breastfeeding must be discontinued during treatment with Naglazyme. Consult your doctor or pharmacist before taking any medicine.
Driving and using machines
No studies have been conducted on the effects of this medicine on the ability to drive vehicles or operate machinery.
This medicine contains sodium
Each 5 ml vial contains 0.8 mmol (18.4 mg) of sodium and is administered in a sodium chloride injectable solution of 9 mg/ml. This should be taken into consideration in patients on a controlled-sodium diet.

3. How to administer this medicine

Naglazyme will be administered to you by a doctor or nurse.
The dose you will receive depends on your body weight. The recommended dose is 1 mg/kg body weight administered once a week as an intravenous infusion (given slowly into a vein). Each infusion will last approximately 4 hours. During the first hour, the infusion rate will be slow (approximately 2.5% of the total solution), while the remaining portion (approximately 97.5%) will be administered over the following 3 hours.
If you are given more Naglazyme than you should
Naglazyme is administered under the supervision of a nurse or doctor who will ensure that you receive the correct dose and will take appropriate action if necessary.
If you miss taking this medicine
If you miss an infusion of Naglazyme, contact your doctor. If you have any doubts about how to use this medicine, speak to your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Side effects have been observed mainly during administration of the medicine or shortly afterwards
(“infusion-related reactions”). The most serious side effects have included facial swelling, fever (very common), longer-than-normal intervals between breaths, difficulty breathing, asthma, and hives (common); swelling of the tongue and throat and severe allergic reaction to this medicine (frequency not known).
If you experience any of these reactions, inform your doctor immediately. You may need to be given additional medicines to prevent an allergic reaction (e.g. antihistamines and/or corticosteroids) or to reduce fever (antipyretics).
The most common symptoms of infusion reaction include fever, chills, skin rash, hives, and shortness of breath.

Very common side effects (may affect more than 1 in 10 people):

• Sore throat • Nasal congestion
• Gastroenteritis • Umbilical hernia
• Slowed reflexes • Vomiting
• Headache • Nausea
• Inflammation of the eyes • Itching
• Blurred vision • Pain (including earache, abdominal, joint and chest pain)
• Decreased hearing • High blood pressure
• Malaise

Common side effects (may affect up to 1 in 10 people):

• Tremor • Shortness of breath
• Low blood pressure • Skin flushing
• Cough

Other side effects with frequency not known:

• Shock • Bluish skin
• Tingling • Pale skin
• Decreased heart rate • Low blood oxygen levels
• Increased heart rate • Rapid breathing

If you experience any side effect, including those not listed in this leaflet, tell your doctor immediately. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store this medicine

Keep Naglazyme out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial after the word "EXP.". The expiry date refers to the last day of the month.
Intact 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 standpoint, Naglazyme should be used immediately.
Otherwise, the times and conditions of storage of the solution during administration are the responsibility of the user and should normally not exceed 24 hours at 2 °C - 8 °C, followed by up to 24 hours at room temperature (23 °C - 27 °C).
Do not use Naglazyme if you notice the presence of suspended particles.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package Contents and Other Information

What Naglazyme Contains

• The active substance is galsulfase. Each ml of Naglazyme contains 1 mg of galsulfase. Each 5 ml vial contains 5 mg of galsulfase. Galsulfase is a recombinant form of human N-acetylgalactosamine-4-sulfatase and is produced by recombinant DNA technology using Chinese hamster ovary (CHO) cell lines.
• The excipients are: sodium chloride, monobasic monohydrate sodium phosphate, dibasic heptahydrate sodium phosphate, polysorbate 80, water for injections.

Description of the Appearance of Naglazyme and Contents of the Package
Naglazyme is presented as a concentrate for solution for infusion. The concentrate should be clear to slightly opalescent, colourless to pale yellow, and free from visible suspended particles. The solution must be further diluted before infusion.
Packaging: 1 and 6 vials. Not all pack sizes may be marketed.
Marketing Authorisation Holder Manufacturer
and BioMarin International Limited
BioMarin International Limited Shanbally, Ringaskiddy
Shanbally, Ringaskiddy County Cork, P43 R298
County Cork, P43 R298 Ireland
Ireland
More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu/. In addition, links to other websites on rare diseases and their therapeutic treatments are provided.
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The following information is intended exclusively for physicians or healthcare professionals:
Naglazyme must not be mixed with other medicinal products in the same infusion, except those listed below.
Each Naglazyme vial is for single use only. The concentrate for infusion solution must be diluted in 9 mg/ml (0.9%) sodium chloride solution for infusion using aseptic technique. It is recommended that the diluted Naglazyme solution be administered through an infusion set equipped with an in-line 0.2 µm filter.
Any unused product residue must be disposed of according to local regulations.

Preparation of the Infusion with Naglazyme (use aseptic technique)
Vials to be diluted, the number of which is determined based on the individual patient's body weight, should be removed from the refrigerator approximately 20 minutes before preparation to allow them to reach room temperature. Prior to dilution, each vial must be visually inspected for the presence of suspended particles and discoloration. The solution should be clear to slightly opalescent, colourless to pale yellow, and free from visible suspended particles.
From a 250 ml infusion bag, withdraw and discard a volume of 9 mg/ml (0.9%) sodium chloride solution for infusion equal to the total volume of Naglazyme to be added. For patients susceptible to fluid accumulation and weighing less than 20 kg, 100 ml infusion bags should be considered; in this case, the infusion rate (ml/min) should be reduced so that the total duration of infusion remains no less than 4 hours. When using 100 ml bags, the volume of Naglazyme may be added directly into the infusion bag.
The volume of Naglazyme must be added slowly to the 9 mg/ml (0.9%) sodium chloride solution for infusion.
Before infusion, the solution should be gently mixed.
Before administration, the solution must be visually inspected for the presence of suspended particles. Only clear, colourless solutions free from visible suspended particles should be used.