Vimizim 1 mg/ml concentrate for infusion solution

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Vimizim 1 mg/ml concentrate for solution for infusion

elosulfase alfa

This medicinal product is subject to additional monitoring, which will allow quicker identification of new safety information. You can help by reporting any side effects you may experience. Section 4 at the end of this leaflet includes information on how to report side effects.

Read the entire leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor.
• If you experience any side effects, consult your doctor, even if they are not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Vimizim is and what it is used for

Vimizim contains an enzyme called elosulfase alfa, which belongs to a group of medicines known as enzyme replacement therapies. It is used to treat adults and children with mucopolysaccharidosis type IVA (MPS IVA disease, also known as Morquio A syndrome).

People with MPS IVA disease either completely lack or do not have sufficient levels of N-acetylgalactosamine-6-sulfatase, an enzyme that breaks down specific substances in the body, such as keratan sulfate, which are found in many tissues of the body, including cartilage and bone. As a result, these substances are not degraded or processed by the body as they should be. They accumulate in tissues, interfere with their normal function, and cause the symptoms of MPS IVA, such as difficulty walking, breathing problems, short stature, and hearing loss.

How Vimizim works

This medicine replaces the naturally missing enzyme, N-acetylgalactosamine-6-sulfatase, in patients with MPS IVA. Treatment has been shown to improve walking ability and reduce levels of keratan sulfate in the body. This medicine may improve the symptoms of MPS IVA.

2. What you need to know before receiving Vimizim

Do not receive Vimizim

• if you have experienced potentially life-threatening allergic reactions to elosulfase alfa or to any of the other components of this medicine (listed in section 6).

Warnings and precautions

• If you are treated with Vimizim, you may develop infusion-related reactions. An infusion reaction is any adverse effect, including an allergic reaction, that occurs during the
  infusion or within one day after the infusion (see section 4). If you experience one of these reactions, you must contact your doctor immediately.

• If you have an allergic reaction during the infusion, your doctor may slow down or stop the infusion. Your doctor may also administer additional medications to manage allergic reactions (e.g., antihistamines and/or corticosteroids).

• If you experience back pain, numbness in the arms or legs, or loss of control over urination or defecation, you must contact your doctor immediately.
  These problems may be part of the disease and could be due to pressure on your spinal cord.

Use of Vimizim with other medicines

Inform your doctor if you are taking, have recently taken, or might need to take any other medicines.

Pregnancy, breastfeeding and fertility

You should not receive Vimizim during pregnancy unless clearly necessary. It is unknown whether Vimizim is excreted in human breast milk. Consult your doctor to determine whether the benefits of taking Vimizim outweigh the potential risks to your newborn during breastfeeding. It is unknown whether Vimizim affects human fertility. No effects on fertility were observed in animals.

Driving and use of machines

Dizziness has been reported in some patients during Vimizim infusion. Consult your doctor if you feel dizzy after the infusion, especially before driving or operating any machinery, as dizziness could be dangerous.

Vimizim contains sodium and sorbitol (E420)

This medicine contains 8 mg of sodium (the main component of table salt) in each 5 ml vial. This corresponds to 0.4% of the recommended daily sodium intake for adults.

This medicine contains 100 mg of sorbitol in each 5 ml vial, equivalent to 40 mg/kg. Sorbitol is a source of fructose. If you (or your child) have hereditary fructose intolerance (HFI), a rare genetic disorder in which patients cannot break down fructose, consult your doctor (or your child’s doctor) before receiving this medicine.

Consult your doctor before receiving this medicine if you (or your child) have HFI or cannot consume sweet foods or drinks because they cause dizziness, vomiting, or unpleasant effects such as bloating, stomach cramps, or diarrhea.

3. How Vimizim is administered

Your doctor or nurse will administer Vimizim to you by intravenous infusion (a drip into a vein).

The medicine must be diluted before administration. Your doctor or nurse will give you certain medications before treatment to reduce allergic reactions, and may also administer medications to help control fever.

Dosage

The dose you receive depends on your body weight. The recommended dose for adults and children is 2 mg/kg body weight administered once weekly by intravenous infusion (drip into a vein). Each infusion will be given over approximately 4 hours. Treatment with Vimizim may be initiated as early as possible and is intended for long-term use.

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

4. Possible adverse effects

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

Adverse effects were mainly observed while patients were receiving the infusion or immediately after ("infusion reactions"). The most serious adverse effects were severe allergic reactions (seen uncommonly; may affect up to 1 in 100 people) and mild to moderate vomiting (seen very commonly; may affect more than 1 in 10 people). Symptoms of an allergic reaction include rash, itching, or skin eruptions (seen commonly; may affect up to 1 in 10 people). If you experience any difficulty swallowing or speaking, severe shortness of breath or wheezing, swelling of the face or lips, dizziness, or weak pulse, these may be symptoms of a severe allergic reaction and you must inform your doctor immediately. Depending on the severity of the adverse reaction, your doctor may slow down or temporarily interrupt the infusion and/or administer additional medicines to reduce the effects of a severe allergic reaction (e.g., antihistamines and/or corticosteroids) or to reduce fever (antipyretics).

Very common adverse effects include symptoms of infusion reactions such as headache, nausea, fever, chills, and stomach pain. Other very common adverse reactions were diarrhea, mouth and throat pain, dizziness, and breathing difficulties.

Common adverse effects included muscle pain.

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system detailed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Vimizim

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the carton and vial after EXP. The expiry date is the last day of the month indicated.

Closed vials:

Store in a refrigerator (2°C – 8°C).

Do not freeze.

Keep in the original packaging to protect from light.

Do not use Vimizim if the solution is discolored or contains visible particles.

After dilution:

Once diluted, the product should be used immediately. If not used immediately, the storage conditions and duration of stability in use are the responsibility of the user, and normally should not exceed 24 hours at a temperature between 2°C – 8°C, followed by a period of up to 24 hours between 23°C and 27°C during administration.

Medicines must 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 container and other information

Composition of Vimizim

• The active substance is elosulfase alfa. Each ml of concentrate contains 1 mg of elosulfase alfa. Each 5 ml vial contains 5 mg of elosulfase alfa.

• The other components are: sodium acetate trihydrate, sodium dihydrogen phosphate monohydrate, arginine hydrochloride, sorbitol, polysorbate 20, and water for injections (see section 2: “Vimizim contains sodium and sorbitol (E420)”).

Appearance of the product and contents of the pack

Vimizim is presented as a concentrate for solution for infusion (sterile concentrate). The clear to slightly opalescent, colourless to pale yellow concentrate must not contain visible particles.

Presentation: 1 vial of 5 ml

Marketing Authorisation Holder

BioMarin International Limited
Shanbally, Ringaskiddy
County Cork, P43 R298
Ireland

Manufacturer

BioMarin International Limited
Shanbally, Ringaskiddy
County Cork, P43 R298
Ireland

Date of the most recent revision of this leaflet MM/YYYY

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

<------------------------------------------------------------------------------------------------------------------------>

This information is intended for healthcare professionals only:

Vimizim must not be mixed with any other medicinal product in the same infusion, except as mentioned below.

Each vial of Vimizim is for single use only. Vimizim must be diluted with sodium chloride solution 9 mg/ml (0.9%) for infusion using an aseptic technique. The diluted Vimizim solution should be administered to patients via an infusion set. An infusion set equipped with an in-line 0.2 µm filter may be used.

Disposal of any unused product and of all materials that have come into contact with it must be carried out in accordance with local requirements.

Preparation of Vimizim infusion (use aseptic technique)

1. Determine the number of vials to be diluted based on the individual patient's body weight, and remove them from the refrigerator in advance to allow them to reach 23 °C – 27 °C. Do not heat vials or place them in a microwave. The recommended dose is 2 mg/kg body weight administered once weekly by intravenous infusion over approximately 4 hours.

• Patient weight (kg) multiplied by 2 (mg/kg) = Patient dose (mg)

• Patient dose (mg) divided by 1 (mg/ml Vimizim concentrate) = Total number of ml of Vimizim

• Total amount (ml) of Vimizim divided by 5 ml per vial = Total number of vials

1. The total number of vials calculated should be rounded up to the next whole vial.

2. Obtain an infusion bag containing sodium chloride solution 9 mg/ml (0.9%) for infusion suitable for intravenous administration. The total infusion volume is determined according to the patient's body weight.

• Patients weighing less than 25 kg should receive a total volume of 100 ml.
• Patients weighing 25 kg or more should receive a total volume of 250 ml.

1. Before dilution, inspect each vial for the presence of particles and discoloration. The solution, which is clear to slightly opalescent and colourless to pale yellow, must not contain visible particles. Do not shake the vials.

2. Withdraw and discard a volume of sodium chloride solution 9 mg/ml (0.9%) for infusion from a 100 ml or 250 ml infusion bag equal to the total volume of Vimizim to be added.

3. Slowly withdraw the calculated volume of Vimizim from the appropriate number of vials, taking care to avoid excessive agitation.

4. Slowly add the volume of Vimizim to the sodium chloride solution 9 mg/ml (0.9%) for infusion.

When diluted with 100 ml of sodium chloride solution 9 mg/ml (0.9%) for infusion: the initial infusion rate will be 3 ml/h. The infusion rate should be increased every 15 minutes as follows: first increase the rate to 6 ml/h, then increase the rate every 15 minutes by increments of 6 ml/h until a maximum rate of 36 ml/h is reached.

When diluted with 250 ml of sodium chloride solution 9 mg/ml (0.9%) for infusion: the initial infusion rate will be 6 ml/h. The infusion rate should be increased every 15 minutes as follows: first increase the rate to 12 ml/h, then increase the rate every 15 minutes by increments of 12 ml/h until a maximum rate of 72 ml/h is reached.

The infusion rate may be increased according to patient tolerance.

1. The diluted solution should be gently mixed before infusion.

2. The diluted solution should be inspected visually for particles prior to use. Do not use if the solution shows discoloration or particles.

3. The diluted solution should be used immediately. If not used immediately, the in-use storage times and conditions are the responsibility of the user, and normally should not exceed 24 hours at 2 °C – 8 °C, followed by up to 24 hours at 23 °C – 27 °C during administration.