Vimizim

Helstu upplýsingar

  • Heiti vöru:
  • Vimizim
  • Lyf við lungum:
  • Mannfólk
  • Lyfjaform:
  • Allópatísk lyf

Skjöl

Staðsetning

  • Fáanlegt í:
  • Vimizim
    Evrópusambandið
  • Tungumál:
  • enska

Meðferðarupplýsingar

  • Meðferðarhópur:
  • Other alimentary tract and metabolism products,
  • Lækningarsvæði:
  • Mucopolysaccharidosis IV
  • Ábendingar:
  • Vimizim is indicated for the treatment of mucopolysaccharidosis, type IVA (Morquio A Syndrome, MPS IVA) in patients of all ages.
  • Vörulýsing:
  • Revision: 11

Staða

  • Heimild:
  • EMA - European Medicines Agency
  • Leyfisstaða:
  • Authorised
  • Leyfisnúmer:
  • EMEA/H/C/002779
  • Leyfisdagur:
  • 26-04-2014
  • EMEA númer:
  • EMEA/H/C/002779
  • Síðasta uppfærsla:
  • 25-03-2019

Opinber matsskýrsla

7 Westferry Circus

Canary Wharf

London E14 4HB

United Kingdom

An agency of the European Union

Telephone

+44 (0)20 7418 8400

Facsimile

+44 (0)20 7418 8416

E-mail

info@ema.europa.eu

Website

www.ema.europa.eu

© European Medicines Agency, 2014. Reproduction is authorised provided the source is acknowledged.

EMA/109796/2014

EMEA/H/C/002779

EPAR summary for the public

Vimizim

elosulfase alfa

This is a summary of the European public assessment report (EPAR) for Vimizim. It explains how the

Agency assessed the medicine to recommend its authorisation in the EU and its conditions of use. It is

not intended to provide practical advice on how to use Vimizim.

For practical information about using Vimizim, patients should read the package leaflet or contact their

doctor or pharmacist.

What is Vimizim and what is it used for?

Vimizim is a medicine that contains the active substance elosulfase alfa. It is used to treat patients

with mucopolysaccharidosis type IVA (MPS IVA, also known as Morquio A syndrome). This disease is

caused by the lack of an enzyme called N-acetylgalactosamine-6-sulfatase, which is needed to break

down substances in the body called glycosaminoglycans (GAGs). If the enzyme is not present, or only

present in very small quantities, GAGs cannot be broken down and they build up in bones and organs.

This causes the signs of the disease, the most noticeable being short bones, difficulty moving and

breathing, clouding of the eyes and hearing loss.

Because the number of patients with MPS IVA is low, the disease is considered ‘rare’, and Vimizim was

designated an ‘orphan medicine’ (a medicine used in rare diseases) on 24 July 2009.

How is Vimizim used?

Treatment with Vimizim should be supervised by a doctor experienced in MPS IVA or similar diseases.

The medicine can only be obtained with a prescription and should be given by an appropriately trained

healthcare professional.

Vimizim is available as a concentrate to be made into a solution for infusion (drip) into a vein. The

recommended dose is 2 mg per kilogram body weight, given once a week. The infusion should last

Vimizim

EMA/109796/2014

Page 2/3

around 4 hours. Before receiving Vimizim, the patient should be given a medicine to prevent an allergic

reaction to Vimizim. Patients may also be given a medicine to prevent fever.

How does Vimizim work?

Vimizim is an enzyme replacement therapy. Enzyme replacement therapy provides patients with the

enzyme they are lacking. The active substance in Vimizim, elosulfase alfa, is a copy of the human

enzyme N-acetylgalactosamine-6-sulfatase. The replacement enzyme helps to break down GAGs and

stop them building up in cells, thereby improving the symptoms of MPS IVA.

Elosulfase alfa is produced by a method known as ‘recombinant DNA technology’: it is made by cells

into which a gene (DNA) has been introduced, which makes them able to produce the enzyme.

What benefits of Vimizim have been shown in studies?

Vimizim has been investigated in one main study involving 176 patients with MPS IVA, which compared

Vimizim with placebo (a dummy treatment). The main measure of effectiveness was the change in the

distance patients could walk in six minutes after 6 months of treatment.

Before treatment, the patients could walk on average just over 200 metres in six minutes. After 6

months, patients treated with the recommended dose of Vimizim could walk an extra 37 metres on

average in six minutes, compared with an increase of 14 metres in patients receiving placebo. Study

results also suggested that the medicine could improve how well patients breathe or climb stairs, and

in children, how well they grew.

What are the risks associated with Vimizim?

The most common side effects with Vimizim (which may affect more than 1 in 10 people) are infusion-

related reactions, including headache, nausea (feeling sick), vomiting, fever, chills and abdominal pain

(stomach ache). These are usually mild or moderate and more frequent in the first 12 weeks of

treatment. Serious but uncommon infusion-related reactions include anaphylaxis (severe allergic

reaction). For the full list of all side effects reported with Vimizim, see the package leaflet.

Vimizim must not be used in patients who have experienced life-threatening allergic reactions to

elosulfase alfa or any of the other ingredients in Vimizim.

Why is Vimizim approved?

The Agency’s Committee for Medicinal Products for Human Use (CHMP) decided that Vimizim’s benefits

are greater than its risks and recommended that it be approved for use in the EU. The CHMP concluded

that, following 6 months of treatment, Vimizim was shown to be effective at improving the distance

patients could walk in six minutes, and this was accompanied by other beneficial effects, including

improved ability to carry out daily activities. The Committee also considered that the safety profile of

Vimizim appears manageable and serious side effects are uncommon, but further long-term safety

data are to be collected.

What measures are being taken to ensure the safe and effective use of

Vimizim?

A risk management plan has been developed to ensure that Vimizim is used as safely as possible.

Based on this plan, safety information has been included in the summary of product characteristics and

Vimizim

EMA/109796/2014

Page 3/3

the package leaflet for Vimizim, including the appropriate precautions to be followed by healthcare

professionals and patients.

In addition, the company that makes Vimizim must ensure that all healthcare professionals expected to

prescribe or use the medicine are provided with educational material, informing them of how the

medicine should be used and the risk of severe allergic reactions. The company will also set up a

registry to assess the long-term benefits and risks of Vimizim.

Further information can be found in the summary of the risk management plan

Other information about Vimizim

The European Commission granted a marketing authorisation valid throughout the European Union for

Vimizim on 28 April 2014.

The full EPAR and risk management plan summary for Vimizim can be found on the Agency’s website:

ema.europa.eu/Find medicine/Human medicines/European public assessment reports. For more

information about treatment with Vimizim, read the package leaflet (also part of the EPAR) or contact

your doctor or pharmacist.

The summary of the opinion of the Committee for Orphan Medicinal Products for Vimizim can be found

on the Agency’s website: ema.europa.eu/Find medicine/Human medicines/Rare disease designation.

This summary was last updated in 04-2014.

Upplýsingar um fylgiseðil sjúklinga: samsetning, vísbendingar, aukaverkanir, skammtar, milliverkanir, aukaverkanir, meðgöngu, brjóstagjöf

B. PACKAGE LEAFLET

Package leaflet: Information for the user

Vimizim 1 mg/ml concentrate for solution for infusion

elosulfase alfa

▼This medicine is subject to additional monitoring. This will allow quick identification of new safety

information. You can help by reporting any side effects you may get. See the end of section 4 for how

to report side effects.

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 further questions, ask your doctor.

If you get any side effects, talk to your doctor. This includes any possible side effects not listed

in this leaflet. See section 4.

What is in this leaflet

What Vimizim is and what it is used for

What you need to know before you are given Vimizim

How Vimizim is given

Possible side effects

How to store Vimizim

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 lack completely or do not have enough N-acetylgalactosamine-6-

sulfatase, an enzyme which breaks down specific substances in the body such as keratan sulphate,

which are found in many tissues of the body, including cartilage and bone. As a result, these

substances do not get broken down and processed by the body as they should. They accumulate in the

tissues interfering with their normal function and causing the symptoms of MPS IVA, such as

difficulty walking, trouble breathing, short height, and hearing loss.

How Vimizim works

This medicine replaces the natural enzyme N-acetylgalactosamine-6-sulfatase which is lacking in

MPS IVA patients. Treatment has been shown to improve walking and to reduce the levels of keratan

sulphate in the body. This medicine may improve the symptoms of MPS IVA.

2.

What you need to know before you are given Vimizim

You must not receive Vimizim

if you have experienced life-threatening allergic reactions to elosulfase alfa or any of the other

ingredients of this medicine (listed in section 6).

Warnings and precautions

If you are treated with Vimizim, you may develop infusion reactions. An infusion reaction is any

side effect, including an allergic reaction, occurring during the infusion or within a day following

infusion (see section 4). If you experience such a reaction,

you should immediately contact your

doctor.

If you have an allergic reaction during your infusion your doctor may slow down, or stop your

infusion. Your doctor may also give you additional medicines to manage any allergic reactions

(e.g. antihistamines and/or corticosteroids).

If you experience back pain, numbness in your arms or legs, or lack of control over passing urine

or stools

, you should immediately contact your doctor

These problems can be a part of the

disease and may be caused by pressure on your spinal cord.

Other medicines and Vimizim

Please tell your doctor if you are taking, have recently taken or might take any other medicines.

Pregnancy, breast-feeding and fertility

You should not receive Vimizim during pregnancy unless clearly necessary. It is not known whether

Vimizim is excreted in breast milk. Discuss with your doctor if the benefits of taking Vimizim are

greater than the potential risk to your newborn while breast-feeding. It is not known if Vimizim

impacts human fertility. No effect on fertility was observed in animals.

Driving and using machines

Dizziness was reported in some patients during the Vimizim infusion. Tell your doctor if you feel

dizzy after your infusion, especially before driving or using any machine where dizziness might be

dangerous.

Vimizim contains sodium and sorbitol (E 420)

This medicine contains 8 mg sodium (main component of cooking/table salt) in each 5 ml vial. This is

equivalent to 0.4 % of the recommended daily dietary intake of sodium for an adult.

This medicine contains 100 mg sorbitol in each 5 ml vial which is 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, you (or your child) must not receive this medicine unless discussed with your doctor.

Patients with HFI cannot break down fructose, which may cause serious side effects.

You must tell your doctor before receiving this medicine if you (or your child) have HFI or if your

child can no longer take sweet foods or drinks because they feel sick, vomit or get unpleasant effects

such as bloating, stomach cramps or diarrhoea.

3.

How Vimizim is given

Your doctor or nurse will give Vimizim to you by an infusion into a vein.

The medicine has to be diluted before being given. Your doctor or nurse will give you some medicines

before your treatment to reduce allergic reactions and you may also be given medicines to help control

any fever.

Dose

The dose you receive is based on your body weight. The recommended dose regimen for adults and

children is 2 mg/kg body weight given once every week through a drip into a vein (intravenous

infusion). Each infusion will be given over approximately 4 hours. Treatment with Vimizim may be

started at as young as an age possible and is intended for long term use.

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

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 given the medicine or shortly after (“infusion

reactions”). The most serious side 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 allergic reaction include rash, itching or hives on the skin (seen

commonly – may affect up to 1 in 10 people).

If you experience any difficulty swallowing, talking,

severe shortness of breath or wheezing, swelling of the face or lips, dizziness or weak pulse; these

may represent symptoms of a severe allergic reaction

and you should tell your doctor

immediately

. Based on the severity of the side effect, your doctor may slow or temporarily interrupt

the infusion and/ or give you additional medicines to reduce the effects of a severe allergic reaction

(e.g. antihistamines and/or corticosteroids) or to reduce fever (antipyretics).

Very common side effects include symptoms of infusion reactions such as headache, nausea, fever,

chills and stomach ache. Other very common adverse reactions were diarrhoea, mouth and throat pain,

dizziness and trouble breathing.

Common side effects observed was muscle pain.

Reporting of side effects

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not

listed in this leaflet. You can also report side effects directly via 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.

How to store Vimizim

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 carton and vial after EXP. The

expiry date refers to the last day of that month.

Unopened vials:

Store in a refrigerator (2

C – 8

Do not freeze.

Store in the original package in order to protect from light.

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

After dilution:

Once the product has been diluted it should be used immediately. If not used immediately, in-use

storage times and conditions are the responsibility of the user and should normally not be longer than

24 hours at 2

C – 8

C followed by up to 24 hours at 23

C – 27

C during administration.

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.

6.

Contents of the pack and other information

What Vimizim contains

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

Each vial of 5 ml contains 5 mg elosulfase alfa.

The other ingredients are: sodium acetate trihydrate, sodium dihydrogen phosphate

monohydrate, arginine hydrochloride, sorbitol, polysorbate 20, and water for injections (see

section 2 under ‘Vimizim contains sodium and sorbitol (E420)’).

What Vimizim looks like and contents of the pack

Vimizim is supplied as a concentrate for solution for infusion (sterile concentrate). The clear to

slightly opalescent and colourless to pale yellow concentrate must be free of visible particles.

Pack sizes: 1 vial of 5 ml

Marketing Authorization Holder

BioMarin International Limited

Shanbally, Ringaskiddy

County Cork, P43 R298

Ireland

Manufacturer

BioMarin International Limited

Shanbally, Ringaskiddy

County Cork

Ireland

This leaflet was last revised in MM/YYYY

Detailed information on this medicine is available on the European Medicines Agency web site:

http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments.

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

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

Vimizim should not be mixed with other medicinal products in the same infusion, except for those

mentioned below.

Each vial of Vimizim is intended for single use only. Vimizim has to be diluted with sodium chloride

9 mg/ml (0.9 %) solution for infusion using aseptic technique. Diluted Vimizim solution is to be

administered to patients using an infusion set. An infusion set equipped with an in-line 0.2 µm filter

can be used.

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

Preparation of the Vimizim 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 in advance in order to allow them to reach 23

C – 27

C. Do not heat

or microwave vials. The recommended dose regimen is 2 mg/kg body weight administered once

every week through a drip into a vein (by intravenous infusion). Each infusion will take

approximately 4 hours.

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

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

Vimizim

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

The calculated total number of vials is rounded up to next whole vial.

An infusion bag containing sodium chloride 9 mg/ml (0.9 %) solution for infusion is obtained

suitable for intravenous administration. The total volume of the infusion is determined by 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.

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. Do not

shake vials.

A volume of the sodium chloride 9 mg/ml (0.9 %) solution for infusion is to be withdrawn and

discarded from a 100 ml or 250 ml infusion bag equal to the total volume of Vimizim to be added.

The calculated volume of Vimizim from the appropriate number of vials is slowly withdrawn using

caution to avoid excessive agitation.

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

infusion.

When diluted with 100 ml sodium chloride 9 mg/ml (0.9 %) solution for infusion;

the initial

rate will be 3 ml/hr. The infusion rate will be increased every 15 minutes as follows: first increase

the rate to 6 ml/hr, then increase the rate every 15 minutes by 6 ml/hr increments until a maximum

rate of 36 ml/hr is reached.

When diluted with 250 ml sodium chloride 9 mg/ml (0.9 %) solution for infusion;

the initial

rate will be 6 ml/hr. The infusion rate will be increased every 15 minutes as follows: first increase

the rate to 12 ml/hr, then increase the rate every 15 minutes by 12 ml/hr increments until a

maximum rate of 72 ml/hr is reached.

Patient

weight

(kg)

Total

infusion

volume

(ml)

Step 1

Initial

infusion

rate 0-15

minutes

(ml/hr)

Step 2

15-30

minutes

(ml/hr)

Step 3

30-45

minutes

(ml/hr)

Step 4

45-60

minutes

(ml/hr)

Step 5

60-75

minutes

(ml/hr)

Step 6

75-90

minutes

(ml/hr)

Step 7

90+

minutes

(ml/hr)

< 25

≥ 25

Infusion rate may be increased as tolerated by patient.

The diluted solution is to be mixed gently prior to infusion.

The diluted solution is to be visually inspected for particulate matter prior to use. Do not use if the

solution is discoloured or if there is particulate matter in the solution

The diluted solution should be used immediately. If not used immediately, in-use storage times and

conditions are the responsibility of the user and should normally not be longer than 24 hours

at 2

C – 8

C followed by up to 24 hours at 23

C – 27

C during administration.