This is a summary of the European public assessment report (EPAR) for Methylthioninium chloride Proveblue. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Methylthioninium chloride Proveblue.
- What is Methylthioninium chloride Proveblue?
Methylthioninium chloride Proveblue is a solution for injection that contains the active substance methylthioninium chloride (5 mg/ml).
Methylthioninium chloride Proveblue is a ‘hybrid generic 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.
- What is Methylthioninium chloride Proveblue used for?
Methylthioninium chloride Proveblue is used in adults and children of all ages as an antidote to treat symptoms of methaemoglobinaemia caused by exposure to medicines or chemicals.
Methaemoglobinaemia is a condition where there is too much of an abnormal form of haemoglobin 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.
The medicine can only be obtained with a prescription.
- How is Methylthioninium chloride Proveblue used?
Methylthioninium chloride Proveblue is injected slowly into a vein over a period of five minutes. It must be given by a healthcare professional.
The usual dose for adults and children aged above three months is 1 to 2 mg per 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 (Fe2+). Exposure to certain medicines or chemicals can cause the iron in the haemoglobin to change to the ‘ferric’ form (Fe3+) seen in methaemoglobinaemia.
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.
- How has Methylthioninium chloride Proveblue been studied?
Because methylthioninium chloride has been used in the European Union for several decades to treat methaemoglobinaemia, the company presented data on the use of methylthioninium chloride from published literature.
- What benefit has Methylthioninium chloride Proveblue shown during the studies?
Reports from published literature 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 is the risk associated with Methylthioninium chloride Proveblue?
The most common side effects with methylthioninium chloride are nausea (feeling sick), abdominal and chest pain, headache, dizziness, tremors, anxiety, confusional state, dyspnoea (difficulty breathing), tachycardia (rapid heartbeat), hypertension (high blood pressure), hyperhidrosis (excessive sweating), pain at the site of injection or in a limb, and the formation of methaemoglobinaemia. 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.
- Why has Methylthioninium chloride Proveblue been 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?
A risk management plan has been developed to ensure that Methylthioninium chloride Proveblue is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Methylthioninium chloride Proveblue, including the appropriate precautions to be followed by healthcare professionals and patients.
- 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.
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 EPAR was last updated on 13/06/2016 .
20/05/2016 Methylthioninium chloride Proveblue -EMEA/H/C/002108 -N/0031
- Annex I - Summary of product characteristics
- Annex IIA - Manufacturing-authorisation holder responsible for batch release
- Annex IIB - Conditions of the marketing authorisation
- Annex IIIA - Labelling
- Annex IIIB - Package leaflet
Please note that the size of the above document can exceed 50 pages.
You are therefore advised to be selective about which sections or pages you wish to print.
All other therapeutic products
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).
Changes since initial authorisation of medicine
|Name||Language||First published||Last updated|
|Methylthioninium chloride Proveblue : EPAR - Procedural steps taken and scientific information after authorisation||HR = Hrvatski||28/02/2012||13/06/2016|
|Methylthioninium chloride Proveblue-H-C-PSUSA-00002029-201505 : EPAR - Scientific conclusions and grounds recommending the variation to the terms of the marketing authorisation||HR = Hrvatski||21/03/2016|
Initial marketing-authorisation documents
|Name||Language||First published||Last updated|
|Methylthioninium chloride Proveblue : EPAR - Public assessment report||HR = Hrvatski||06/06/2011|
|CHMP summary of positive opinion for Methylthioninium chloride Proveblue||HR = Hrvatski||18/02/2011|