Methylthioninium chloride Proveblue 5 mg/ml solution for injection

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Proveblue Methylene blue chloride 5 mg/ml solution for injection

Methylene blue chloride

Read the entire leaflet carefully before receiving 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 or nurse.
• If you experience any adverse effects, consult your doctor or nurse, even if the adverse effects are not listed in this leaflet. See section 4.

Contents of the package leaflet:

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

1. What Cloruro de metiltionio Proveblue is and what it is used for

Methylthioninium chloride (also known as methylene blue) belongs to a group of medicines called antidotes.

Cloruro de metiltionio Proveblue will be administered to you or your child (0–17 years of age) to treat blood disorders caused by exposure to certain medications or chemicals that can lead to a condition called methemoglobinemia.

In methemoglobinemia, the blood contains an excessive amount of methemoglobin (an abnormal form of hemoglobin that is unable to effectively carry oxygen throughout the body).

This medicine will help normalize hemoglobin and restore oxygen transport in the blood.

2. What you need to know before receiving Cloruro de metiltionio Proveblue

Do not receive Cloruro de metiltionio Proveblue:

• if you are allergic to methylene blue chloride or to other dyes derived from thiazine
• if your body does not produce sufficient amounts of the enzyme G6PD (glucose-6-phosphate dehydrogenase)
• if your body does not produce sufficient amounts of the enzyme NADPH (nicotinamide adenine dinucleotide phosphate) reductase
• if the blood disorder was caused by nitrite during treatment of cyanide poisoning
• if the blood disorder was caused by chlorate poisoning.

Warnings and precautions

Consult your doctor or nurse before receiving Cloruro de metiltionio Proveblue

• if you have moderate or severe kidney disease; a dose reduction may be necessary (< 1 mg/kg)

• if your blood disorder has been caused by a chemical called aniline, found in dyes; a dose reduction may be necessary, and the total cumulative dose must not exceed 4 mg/kg (see section 3 of this leaflet)

• if your blood disorder has been caused by a medicine called dapsone (used to treat leprosy and other skin diseases); a dose reduction may be necessary, and the total cumulative dose must not exceed 4 mg/kg (see section 3)

• if you have hyperglycemia or diabetes mellitus, as these conditions could worsen due to the glucose solution used to dilute the medicine

• urine and feces may turn blue-green, and skin may appear bluish during treatment with Cloruro de metiltionio Proveblue. This color change is expected and will disappear once treatment is completed.

If any of the above situations apply to you, consult your doctor.

Photosensitivity

Methylthioninium chloride may cause a photosensitivity reaction in the skin (a sunburn-like reaction) when exposed to intense light sources, such as phototherapy, operating room lights, and pulse oximeters.

Protective measures against light exposure should be taken.

Control Tests

You will undergo control tests during and after treatment with Methylthioninium chloride Proveblue.

Children

Special caution is required with Methylthioninium chloride Proveblue:

• lower doses are recommended in newborns and infants aged 3 months or less (see section 3 of this leaflet).

Other medicines and Methylene Blue Chloride Proveblue

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

You must not receive Methylene Blue Chloride if you are taking certain medicines used to treat depression or anxiety that affect a brain chemical called serotonin. If used together with these medicines, methylene blue chloride may cause serotonin syndrome, which can be potentially fatal. These medicines are:

• Selective serotonin reuptake inhibitors (SSRIs) such as citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and zimeldine
• bupropion
• buspirone
• clomipramine
• mirtazapine
• venlafaxine
• monoamine oxidase inhibitors

However, if intravenous administration of Methylene Blue Chloride cannot be avoided, you should be given the lowest possible dose and kept under observation for 4 hours after administration.

If you have any doubts about whether you should receive this medicine, consult your doctor.

Pregnancy and lactation

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor before receiving this medicine.

The use of Methylthioninium chloride Proveblue during pregnancy is not recommended unless clearly necessary, for example, in a potentially life-threatening situation.

Due to lack of data on whether methylthioninium chloride is excreted in human milk, breastfeeding should be discontinued for 8 days after treatment with this medicine.

Driving and operating machinery

Do not drive or operate tools or machinery, as methylthioninium chloride has a moderate influence on the ability to drive and operate machinery.

3. How Proveblue methylene blue chloride is administered

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

Adults, children over 3 months of age, and elderly

The usual dose is 1 to 2 mg per kilogram of body weight, i.e. 0.20 to 0.4 ml per kilogram, administered over a period of 5 minutes. A second dose may be given after one hour if necessary.

The maximum recommended cumulative dose throughout treatment is 7 mg/kg.

If the blood disorder has been caused by aniline or dapsone, the total cumulative dose must not exceed 4 mg/kg (see section 2).

Generally, treatment should not last longer than 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, administered 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 if symptoms persist or recur. Generally, treatment should not last longer than one day.

This medicine may be diluted in 50 ml of 5% glucose injection solution (50 mg/ml) to avoid local pain, especially in children.

If you are given more Cloruro de metiltioninio Proveblue than you should

Since this medicine will be administered to you while you are in the hospital, it is unlikely that you will receive too much or too little. However, inform your doctor if you notice any of the following adverse reactions:

• nausea
• stomach pain
• chest pain
• dizziness
• headache
• sweating
• confusion
• increased methemoglobin (an abnormal form of hemoglobin in the blood)
• high blood pressure
• difficulty breathing
• abnormally fast heartbeat
• tremor
• changes in skin color (the skin may appear bluish)
• reduction in the number of red blood cells, which may cause paleness, shortness of breath, and weakness
• jaundice (yellowing of the skin and eyes); reported only in infants

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

4. Possible adverse effects

Like all medicines, Methylthioninium chloride Proveblue may cause adverse effects, although not everyone experiences them.

These effects are identical in adults and children, except for jaundice, which has only been reported in infants.

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

• limb pain

• dizziness

• sweating

• skin color changes. The skin may turn blueish

• blue or green urine

  • numbness and tingling
  • abnormal taste in the mouth
  • nausea

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

• stomach pain

• chest pain

• headache

• anxiety

• injection site pain

• vomiting

• Frequency not known (frequency cannot be estimated from the available data):

• serotonin syndrome when Methylthioninium chloride Proveblue is taken with certain medicines used to treat depression or anxiety, see section 2

• reduced levels of hemoglobin (the protein in red blood cells that carries oxygen in the blood) in blood tests

• reduced number of red blood cells, which may cause paleness, shortness of breath, and weakness

• tissue damage at the injection site

• jaundice (yellowing of the skin and eyes); reported only in infants

• difficulty speaking

• increased or decreased blood pressure

• agitation

• lack of oxygen

• irregular heartbeats, including abnormally slow or fast heartbeat

• severe allergic reactions (called anaphylactic reaction, which may cause swelling of the throat or face, difficulty breathing, or severe rash)

• increased methemoglobin (an abnormal form of hemoglobin in the blood)

• breathing difficulty

• confusion

• tremor

• hives

• fever

• rapid breathing

• pupil dilation

• change in stool color. Stools may appear greenish or bluish

• increased skin sensitivity to light (photosensitivity).

Reporting of adverse reactions

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

5. Storage of Methylthioninium chloride Proveblue

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 on the labels of the ampoule, following EXP. The expiry date refers to the last day of the month indicated. The doctor or nurse will check that the expiry date shown on the label has not passed before administering the injection.

Do not refrigerate or freeze. Store the ampoule in the original packaging to protect it from light.

The medicine should be used immediately after opening or dilution.

Do not use Methylthioninium chloride Proveblue if the solution has changed colour, is cloudy, or contains precipitates or particles.

Any unused medicine and all materials that have been in contact with it should be disposed of in accordance with local regulations.

6. Contents of the container and other information

Composition of Methylthioninium Chloride Proveblue

• The active substance is methylthioninium chloride.

Each ml of solution contains 5 mg of methylthioninium chloride. Each 10 ml ampoule contains 50 mg of
methylthioninium chloride. Each 2 ml ampoule contains 10 mg of methylthioninium chloride.

• The other component is water for injections.

Appearance of the product and contents of the container

Methylthioninium chloride Proveblue is a clear, dark blue injectable solution (injection) supplied in clear glass ampoules.

Each carton contains a tray with 5 ampoules of 10 ml. Each carton contains a tray with 5 ampoules of 2 ml. Each carton contains a tray with 20 ampoules of 2 ml.

Marketing Authorization 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 further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Belgium/Belgium/Belgium
Lamepro B.V.
Tél/Tel: +31 (0)76-5600030

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

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

Luxembourg/Luxembourg
Lamepro B.V.
Tél/Tel: +31 (0)76-5600030

Czech Republic
LERAM pharmaceuticals s.r.o
Tel: +420 737 657 454

Hungary
Mediwings Pharma Kft.
Tel.: +36 28 410 463

Denmark
Pharmanovia A/S
Tlf: +45 33 33 76 33

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

Germany
Dr. Franz Köhler Chemie GmbH
Tel: +49 (0)6251-1083-0

Netherlands
Lamepro B.V.
Tel: +31 (0)76-5600030

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

Norway
Pharmanovia A/S
Tlf: +45 33 33 76 33

Greece
VIPharma International SA
Tel: +30-210-6194170

Austria
Dr. Franz Köhler Chemie GmbH
Tel: +49 (0)6251-1083-0

Spain
Fresenius Kabi España, S.A.U.
Tel: +34 93 225 65 65

Poland
AB Pharm Sp. z o.o.
Tel: +48 694 775 205

France
Provepharm SAS
Tél: +33 (0)4 91 08 69 30

Portugal
Labesfal - Laboratórios Almiro
Tel: +351 232 831100

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

Ireland
Laboratoires ETHYPHARM
Tel: +33 1 41 12 65 63

Romania
Dynamic Medical Solutions
Tel: +40 (0)725596648

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

Iceland
Pharmanovia A/S
Sími: +45 33 33 76 33

Slovakia
LERAM pharmaceuticals s.r.o
Tel: +420 737 657 454

Italy
Medac Pharma S.r.l.
Tel: +39 06 51 59 121

Finland
Pharmanovia A/S
Puh/Tel: +45 33 33 76 33

Cyprus
Isangen Pharma Cyprus Ltd
Tel: +357-24-638833

Sweden
Pharmanovia A/S
Tel: +45 33 33 76 33

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

United Kingdom
Martindale Pharmaceuticals Ltd

Tel: + 44 (0)1277 266600

Date of the most recent review of this leaflet:

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu/.

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This information is intended for healthcare professionals only:

Preparation for intravenous administration

Use the product immediately after opening. Inject very slowly over 5 minutes.

Methylthioninium chloride Proveblue is hypotonic and may be diluted in 50 ml of 5% glucose injection solution (50 mg/ml) to avoid local pain, especially in the paediatric population. It must not be diluted in 9 mg/ml (0.9%) sodium chloride injection solution, as chloride has been shown to reduce the solubility of methylthioninium chloride.

Additional information on the administration of Methylthioninium chloride Proveblue is provided in section 3 of the leaflet.

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