Methylthioninium chloride Proveblue

Informazzjoni prinċipali

  • Isem kummerċjali:
  • Methylthioninium chloride Proveblue
  • Dominju tal-mediċina:
  • Bnedmin
  • Tip ta 'mediċina:
  • Droga allopatika

Dokumenti

Lokalizzazzjoni

  • Disponibbli fi:
  • Methylthioninium chloride Proveblue
    Unjoni Ewropea
  • Lingwa:
  • Ingliż

Informazzjoni terapewtika

  • Grupp terapewtiku:
  • ALL OTHER THERAPEUTIC PRODUCTS
  • Żona terapewtika:
  • Methemoglobinemia
  • Indikazzjonijiet terapewtiċi:
  • Acute symptomatic treatment of medicinal and chemical products- induced methaemoglobinaemia.Methylthioninium chloride Proveblue is indicated in adults, children and adolescents (aged 0 to 17 years old).
  • Sommarju tal-prodott:
  • Revision: 19

Status

  • Sors:
  • EMA - European Medicines Agency
  • L-istatus ta 'awtorizzazzjoni:
  • Authorised
  • Numru ta 'awtorizzazzjoni:
  • EMEA/H/C/002108
  • Data ta 'l-awtorizzazzjoni:
  • 05-05-2011
  • Kodiċi EMEA:
  • EMEA/H/C/002108
  • L-aħħar aġġornament:
  • 29-03-2019

Rapport ta 'Valutazzjoni Pubblika

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Telephone

+44 (0)20 3660 6000

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Send a question via our website

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© European Medicines Agency, 2018. Reproduction is authorised provided the source is acknowledged.

EMA/657334/2016

EMEA/H/C/002108

EPAR summary for the public

Methylthioninium chloride Proveblue

methylthioninium chloride

This is a summary of the European public assessment report (EPAR) for Methylthioninium chloride

Proveblue. 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 Methylthioninium

chloride Proveblue

For practical information about using Methylthioninium chloride Proveblue, patients should read the

package leaflet or contact their doctor or pharmacist.

What is Methylthioninium chloride Proveblue and what is it used for?

Methylthioninium chloride Proveblue is used in adults and children of all ages as an antidote to treat

symptoms of methaemoglobinaemia caused by the use of certain medicines or chemicals.

Methaemoglobinaemia is a condition where there is too much of an abnormal form of haemoglobin

(called methaemoglobin) in the blood that is not able to transport oxygen effectively. Substances that

may cause methaemoglobinaemia include some antibiotics, local anaesthetics, nitrates in drinking

water and pesticides.

Methylthioninium chloride Proveblue is a ‘hybrid medicine’. This means that it is similar to a reference

medicine, containing the same active substance but in a different concentration. The reference

medicine for Methylthioninium chloride Proveblue is Methylthioninium Chloride Injection USP 1% w/v.

Methylthioninium chloride Proveblue contains the active substance methylthioninium chloride.

Methylthioninium chloride Proveblue

EMA/657334/2016

Page 2/3

How is Methylthioninium chloride Proveblue used?

Methylthioninium chloride Proveblue is available as a solution for injection (5 mg/ml), which is injected

slowly into a vein over a period of five minutes. It can only be obtained with a prescription and must

be given by a healthcare professional.

The usual dose for adults and children aged above three months is 1 to 2 mg per kilogram (kg) body

weight. A repeat dose may be given one hour after the first dose if symptoms persist or come back, or

if the level of methaemoglobin in the blood stays higher than normal.

The dose in children aged three months or less is 0.3 to 0.5 mg/kg. They may also be given a repeat

dose after one hour.

How does Methylthioninium chloride Proveblue work?

To carry oxygen in the blood, haemoglobin needs to contain an atom of iron in the ‘ferrous’ form

). Exposure to certain medicines or chemicals can cause the iron in the haemoglobin to change to

the ‘ferric’ form (Fe

) seen in methaemoglobinaemia which is less able to transport oxygen.

The active substance in Methylthioninium chloride Proveblue, methylthioninium chloride (also called

methylene blue), helps speed up the conversion of abnormal haemoglobin back into normal

haemoglobin. It does this by accepting negatively charged electron particles through an enzyme called

‘NADPH methaemoglobinaemia reductase’. The electrons are then transferred to the iron atoms in the

abnormal haemoglobin, converting them into the normal ferrous form.

What benefits of Methylthioninium chloride Proveblue have been shown in

studies?

Because methylthioninium chloride has been used in the European Union for several decades to treat

methaemoglobinaemia, the company presented data on its use from the published literature, which

confirmed that methylthioninium chloride is effective in treating methaemoglobinaemia that has been

caused by exposure to a medicine or chemical in adults and children.

What are the risks associated with Methylthioninium chloride Proveblue?

The most common side effects with methylthioninium chloride are dizziness, paraesthesia (unusual

sensations like ‘pins and needles’), dysgeusia (taste disturbances), nausea (feeling sick), skin

discoloration, chromaturia (abnormal colouration of the urine), sweating and pain at the site of

injection or in a limb. For the full list of all side effects reported with methylthioninium chloride, see the

package leaflet.

Methylthioninium chloride Proveblue must not be used in people who are hypersensitive (allergic) to

methylthioninium chloride, or to any other thiazine dyes (the group to which methylthioninium chloride

belongs). It must not be used in patients with the following conditions:

glucose-6-phosphate dehydrogenase deficiency (G6PD),

methaemoglobinaemia caused by nitrite during treatment of cyanide poisoning,

methaemoglobinaemia caused by chlorate poisoning,

deficiency in the enzyme NADPH reductase.

Methylthioninium chloride Proveblue

EMA/657334/2016

Page 3/3

Why is Methylthioninium chloride Proveblue approved?

The Committee concluded the long experience with the active substance, methylthioninium chloride,

shows that it is effective in treating methaemoglobinaemia. The CHMP decided that the medicine’s

benefits are greater than its risks and recommended that it be given marketing authorisation.

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

Methylthioninium chloride Proveblue?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe

and effective use of Methylthioninium chloride Proveblue have been included in the summary of

product characteristics and the package leaflet.

Other information about Methylthioninium chloride Proveblue

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

Methylthioninium chloride Proveblue on 6 May 2011.

The full EPAR for Methylthioninium chloride Proveblue 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 Methylthioninium chloride Proveblue, read the package leaflet

(also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 10-2016.

Fuljett ta 'Informazzjoni għall-Pazjent: prodott - kompożizzjoni, indikazzjonijiet, effetti sekondarji, dożaġġ, interazzjonijiet, reazzjonijiet avversi, tqala, treddigħ

B. PACKAGE LEAFLET

Package leaflet: Information for the user

Methylthioninium chloride Proveblue 5 mg/ml solution for injection

Methylthioninium chloride

Read all of this leaflet carefully before you are given 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 or nurse.

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects

not listed in this leaflet. See section 4.

What is in this leaflet

What Methylthioninium chloride Proveblue is and what it is used for

What you need to know before you are given Methylthioninium chloride Proveblue

How Methylthioninium chloride Proveblue is given

Possible side effects

How to store Methylthioninium chloride Proveblue

Contents of the pack and other information

1.

What Methylthioninium chloride Proveblue is and what it is used for

Methylthioninium chloride (also called methylene blue) belongs to a group of medicines called

antidotes.

Methylthioninium chloride Proveblue will be given to you or your child (0-17 years old) to treat

problems with your blood resulting from exposure to some medicines or chemicals that can cause a

disease called methaemoglobinaemia.

In methaemoglobinaemia, your blood contains too much methaemoglobin (an abnormal form of

haemoglobin that is not able to transport oxygen around your body effectively). This medicine will

help your haemoglobin return to normal and restore the transport of oxygen in the blood.

2.

What you need to know before you are given Methylthioninium chloride Proveblue

You must not be given Methylthioninium chloride Proveblue:

if you are allergic to methylthioninium chloride or other thiazine dyes

if your body does not produce enough of the enzyme G6PD (glucose-6-phosphate

dehydrogenase)

if your body does not produce enough of the enzyme NADPH (nicotinamide adenine

dinucleotide phosphate) reductase

if your blood disorder has been caused by nitrite during treatment of cyanide poisoning

if your blood disorder has been caused by chlorate poisoning.

Warnings and precautions

Talk to your doctor or nurse before you are given Methylthioninium chloride Proveblue

if you have moderate or severe renal disease; lower doses (< 1 mg/kg) may be needed

if your blood disorder has been caused by a chemical called aniline, which is contained in dyes;

lower doses may be needed and total cumulative dose should not exceed 4 mg/kg (see section 3

of this package leaflet)

if your blood disorder has been caused by a medicine called dapsone (used to treat leprosy and

other skin conditions); lower doses may be needed and total cumulative dose should not exceed

4 mg/kg (see section 3)

if you suffer from hyperglycaemia or diabetes mellitus, as these conditions may be worsened by

the glucose solution used for the dilution of the medicine

your urine and stools may turn a blue-green colour; and skin may possibly turn a blue colour

when you are treated with Methylthioninium chloride Proveblue. This discolouration is

expected and will disappear after the treatment has ended

If any of the above applies to you, please consult your doctor.

Photosensitivity

Methylthioninium chloride may cause a photosensitivity reaction in the skin (sunburn-like reaction)

when exposed to strong light sources, such as light therapy, lights in operating rooms and pulse

oximeters.

Protective measures against exposure to light should be taken.

Monitoring tests

You will undergo monitoring tests during and after treatment with Methylthioninium chloride

Proveblue.

Children

Special care must be taken with Methylthioninium chloride Proveblue:

in newborns and infants 3 months old or younger, lower doses are recommended (see section 3

of this package leaflet).

Other medicines and Methylthioninium chloride Proveblue

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other

medicines.

You should not be given methylthioninium chloride at the same time you are taking certain medicines

to treat depression or anxiety which affect a brain chemical called serotonin. When used in

combination with these medicines methylthioninium chloride may cause serotonin syndrome, which

can be potentially life-threatening. Such medicines include:

Selective serotonin reuptake inhibitors (SSRIs) such as citalopram, escitalopram, fluoxetine,

fluvoxamine, paroxetine, sertraline and zimelidine

bupropion

buspirone

clomipramine

mirtazapine

venlafaxine

Monoamine oxidase inhibitors

However, if the intravenous use of methylthioninium chloride cannot be avoided, you should be

administered the lowest possible dose and observed closely for up to 4 hours after administration.

If you have any doubts about whether this medicine should be given to you, consult your doctor.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask

your doctor for advice before you are given this medicine.

The use of Methylthioninium chloride Proveblue during pregnancy is not recommended unless it is

clearly necessary, for example in a life-threatening situation.

Due to a lack of available data on whether methylthioninium chloride passes into human breast milk,

breast-feeding should be discontinued for up to 8 days after treatment with this medicine.

Driving and using machines

Do not drive or use any tools or machines as methylthioninium chloride has moderate influence on the

ability to drive and use machines.

3.

How Methylthioninium chloride Proveblue is given

Your doctor will inject this medicine into a vein (intravenously) slowly over a period of 5 minutes.

Adults, children above 3 months and elderly

The usual dose is 1 to 2 mg per kilogram of your body weight, i.e. 0.2 to 0.4 ml per kilogram given

over a period of 5 minutes. A second dose may be given after one hour if required.

The maximum recommended cumulative dose for the course of treatment is 7 mg/kg.

If your blood disorder has been caused by aniline or dapsone, total cumulative dose should not exceed

4 mg/kg (see section 2).

Usually, treatment should not exceed one day.

Infants 3 months old or younger

The recommended dose is 0.3 to 0.5 mg/kg body weight, i.e. 0.06 to 0.1 ml/kg, over a period of

5 minutes.

A repeat dose (0.3 to 0.5 mg/kg body weight, i.e. 0.06-0.1 ml/kg) may be given after one hour in case

of persistence or recurrence of symptoms. Usually, treatment should not exceed one day.

This medicine may be diluted in 50 ml glucose 50 mg/ml (5%) solution for injection to avoid local

pain, in particular in children.

If you are given more Methylthioninium chloride Proveblue than you should

As this medicine will be given to you whilst you are in hospital, it is unlikely that you will be given

too much or too little, however, tell your doctor if you notice one of the following adverse reactions:

feeling sick,

stomach pain,

chest pain,

dizziness,

headache,

sweating,

confusion,

an increase in methaemoglobin (an abnormal form of haemoglobin in the blood),

high blood pressure,

shortness of breath,

abnormally fast beating of the heart,

tremor,

skin discolouration. Your skin may turn blue

reduction in red blood cells which may turn your skin pale and make you breathless and weak,

jaundice (yellowing of the skin and eyes), this has only been reported in infants.

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

4.

Possible side effects

Like all medicines, Methylthioninium chloride Proveblue can cause side effects, although not

everybody gets them.

These effects are the same in adults and children except jaundice which has only been reported in

infants.

Very common side effects

(may affect more than 1 in 10 people)

-

pain in extremity

-

dizziness

sweating

-

skin discolouration. Your skin may turn blue

blue or green urine

-

numbness and tingling

-

abnormal taste in mouth

-

nausea

Common side effects

(may affect up to 1 in 10 people):

stomach pain

chest pain

headache

anxiety

injection site pain

vomiting

Not known

(frequency cannot be estimated from the available data):

serotonin syndrome when Methylthioninium chloride Proveblue has been taken with certain

medicines to treat depression or anxiety, see section 2

decreased haemoglobin (protein in red blood cells that carry oxygen in the blood) levels may be

reported during blood tests

reduction in red blood cells which may turn your skin pale and make you breathless and weak

local tissue damage at the injection site

jaundice (yellowing of the skin and eyes) – this has only been reported in infants

problems with speech

high or low blood pressure

agitation

lack of oxygen

irregular heartbeat, including an abnormally slow or fast beating of the heart

severe allergic reactions (so called anaphylactic reaction which may cause your throat or face to

swell, difficulty breathing or a severe rash)

an increase in methaemoglobin (an abnormal form of haemoglobin in the blood)

shortness of breath

confusion

shaking

hives

fever

rapid breathing

dilated pupils

discoloured stools. They may appear green or blue

increased sensitivity of your skin to light (photosensitivity)

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist 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

Methylthioninium chloride Proveblue

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

You should not be given this medicine after the expiry date which is printed on the carton and the

ampoule labels after EXP. The expiry date refers to the last day of that month. The doctor or nurse

will check that the expiry date on the label has not been passed before administering the injection to

you.

Do not refrigerate or freeze. Keep the ampoule in the original package in order to protect from light.

The medicine must be used immediately after opening or dilution.

Do not use Methylthioninium chloride Proveblue if the solution is discoloured, cloudy, turbid, or a

precipitate or particles are present.

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

6.

Contents of the pack and other information

What Methylthioninium chloride Proveblue contains

The active substance is methylthioninium chloride.

Each ml of solution contains 5 mg methylthioninium chloride.

Each 10 ml ampoule contains 50 mg methylthioninium chloride.

Each 2 ml ampoule contains 10 mg methylthioninium chloride.

The other ingredient is water for injections.

What Methylthioninium chloride Proveblue looks like and contents of the pack

Methylthioninium chloride Proveblue

is a clear dark blue solution for injection (injection) and is

supplied in clear glass ampoules.

Each box contains a tray with 5 ampoules of 10 ml.

Each box contains a tray with 5 ampoules of 2 ml.

Each box contains a tray with 20 ampoules of 2 ml.

Marketing Authorisation Holder

Provepharm SAS

22 rue Marc Donadille, 13013 Marseille, France

Manufacturer

Pierrel S.p.A.

s.s. Appia 7 bis, 46/48 - 81043 Capua, Italy

Cenexi

52, Rue Marcel et Jacques Gaucher, 94120 Fontenay-sous-Bois, France

For any information about this medicine, please contact the local representative of the Marketing

Authorisation Holder:

België/Belgique/Belgien

Lamepro B.V.

Tél/Tel: + 31 (0) 76-5600030

Lietuva

Provepharm SAS

Tel: +33 (0)4 91 08 69 30

България

Provepharm SAS

Teл.: + 33 (0)4 91 08 69 30

Luxembourg/Luxemburg

Lamepro B.V.

Tél/Tel: + 31 (0) 76-5600030

Česká republika

LERAM pharmaceuticals s.r.o

Tel: +420 737 657 454

Magyarország

Mediwings Pharma Kft.

Tel.: + 36 28 410 463

Danmark

Pharmanovia A/S

Tlf: + 45 33 33 76 33

Malta

Provepharm SAS

Tel: + 33 (0)4 91 08 69 30

Deutschland

Dr. Franz Köhler Chemie GmbH

Tel: + 49 (0) 6251-1083-0

Nederland

Lamepro B.V

Tel: + 31 (0) 76-5600030

Eesti

Provepharm SAS

Tel: + 33 (0)4 91 08 69 30

Norge

Pharmanovia A/S

Tlf: + 45 33 33 76 33

Ελλάδα

a VIPharma International AE

Τηλ: + 30-210-6194170

Österreich

Dr. Franz Köhler Chemie GmbH

Tel: + 49 (0) 6251-1083-0

España

Fresenius Kabi España, S.A.U.

Tel: + 34 93 225 65 65

Polska

Provepharm SAS

Tel.: + 33 (0)4 91 08 69 30

France

Medac

Tél: + 33 (0)4 37 66 14 70

Portugal

Labesfal - Laboratórios Almiro

Tel: + 351 232 831100

Hrvatska

Provepharm SAS

Tel: + 33 (0)4 91 08 69 30

Ireland

Martindale Pharmaceuticals Ltd

Tel: + 44 (0)1277 266600

România

Dynamic Medical Solutions

Tel: + 40 (0)725596648

Slovenija

Provepharm SAS

Tel: + 33 (0)4 91 08 69 30

Ísland

Pharmanovia A/S

Sími: + 45 33 33 76 33

Slovenská republika

LERAM pharmaceuticals s.r.o

Tel: +420 737 657 454

Italia

Medac Pharma S.r.l.

Tel: + 39 06 51 59 121

Suomi/Finland

Pharmanovia A/S

Puh/Tel: + 45 33 33 76 33

Κύπρος

Isangen Pharma Cyprus Ltd

Τηλ: + 357-24-638833

Sverige

Pharmanovia A/S

Tel: + 45 33 33 76 33

Latvija

Provepharm SAS

Tel: + 33 (0)4 91 08 69 30

United Kingdom

Martindale Pharmaceuticals Ltd

Tel: + 44 (0)1277 266600

This leaflet was last revised in

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

http://www.ema.europa.eu/.

<--------------------------------------------------------------------------------------------------------------------------

The following information is intended for healthcare professionals only:

Preparation for intravenous administration

Use immediately on opening. Inject very slowly over a period of 5 minutes.

Methylthioninium chloride Proveblue is hypotonic and may be diluted in 50 ml glucose 50 mg/ml

(5%) solution for injection to avoid local pain, in particular in paediatric population.

It must not be diluted with sodium chloride 9 mg/ml (0.9%) solution for injection because it has been

demonstrated that chloride reduces the solubility of methylthioninium chloride.

Additional information on how Methylthioninium chloride Proveblue can be given is provided in

section 3 of the Package Leaflet.

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