Methylthioninium Chloride Buy
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 itsconditions of use. It is not intended to provide practical advice on how to use Methylthioninium chloride Proveblue
methylthioninium chloride buy
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.
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.
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:
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.
Methylthioninium chloride may cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs. Avoid concomitant use of methylthioninium chloride with selective serotonin reupdate inhibitors (SSRIs), serotonin and norepinephrine reupdate inhibitors (SNRIs), and monoamine oxidase inhibitors (see section 4.5).
Patients treated with methylthioninium chloride in combination with serotonergic drugs should be monitored for the emergence of serotonin syndrome. If symptoms of serotonin syndrome occur, discontinue use of methylthioninium chloride, and initiate supportive treatment.
Methylthioninium chloride may cause a cutaneous photosensitivity reaction when exposed to strong light sources, such as phototherapy, those found in operating theatres or locally from illuminating devices such as pulse oximeters.
The administration of methylthioninium chloride has the potential to transiently increase or decrease the clearance of drugs that are primarily metabolised by the enzymes. The clinical consequences are however considered minimal since methylthioninium chloride is used often only once and in an acute emergency setting.
The clinical consequences of the inhibition are not known. The administration of methylthioninium chloride has the potential to transiently increase the exposure of drugs primarily cleared by renal transport involving the OCT2/MATE pathway, including cimetidine, metformin and aciclovir.
Methylthioninium chloride is a substrate of P-glycoprotein (P-gp). The clinical consequences are considered likely to be minimal due to the transient and single dose use that normally occurs in the emergency setting.
There are no adequate data from the use of methylthioninium chloride in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Methylthioninium chloride should not be used during pregnancy unless clearly necessary, e.g. in life-threatening methaemoglobinaemia.
It is unknown whether Methylthioninium Chloride is excreted in human breast milk. The excretion of methylthioninium chloride in milk has not been studied in animals. A risk to the suckling child cannot be excluded. Based on kinetic data, breast-feeding should be discontinued for up to 8 days after treatment with methylthioninium chloride, unless the clinical need clearly outweighs the potential risk.
In patients with methaemoglobinemia, therapeutic doses of Methylthioninium Chloride can lower the levels of methaemoglobin in the red blood cells. It activates a normally dormant reductase enzyme system which reduces the Methylthioninium Chloride to leucomethylthioninium chloride, which in turn is able to reduce methaemoglobin to haemoglobin. However, in large doses, Methylthioninium Chloride can itself produce methaemoglobinemia and the methaemglobin concentration should therefore be closely monitored during treatment. Methylthioninium Chloride is not effective for the treatment of methaemoglobinemia in patients with glucose-6-phosphate dehydrogenase deficiency as these patients have a diminished capacity to reduce Methylthioninium Chloride to leucomethylthioninium chloride. It is also potentially harmful as patients with glucose-6-phosphate dehydrogenase deficiency are particularly susceptible to the haemolytic anaemias induced by Methylthioninium Chloride.
The efficacy of methylthioninium chloride for the treatment of methaemoglobinaemia in the paediatric population was demonstrated in two retrospective studies and one open randomised clinical trial. Case reports of efficacy are also available in literature.
After intravenous administration Methylthioninium Chloride is rapidly taken up by the tissues. The majority of the dose is excreted in the urine, usually in the form of leucomethylthioninium chloride.
About 75% of a single 10 mg oral dose of Methylthioninium Chloride is recovered from the urine, mainly (80%) as leucomethylthioninium chloride. This metabolite is colourless but turns green or blue on exposure to air due to presence of the oxidation product methylene azure (methylthioninium chloride sulphone).
Some evidence of carcinogenic activity of methylthioninium chloride has been shown in male mice and male rats. An equivocal evidence of carcinogenic activity was observed in female mice. No evidence of carcinogenic activity was observed in female rats.
In vitro, methylthioninium chloride has been shown to reduce motility of human sperm in a dose dependant manner. It has also been shown to inhibit the growth of cultured two-cell mouse embryos and the production of progesterone in cultured human luteal cells.
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6. It must especially not be mixed with sodium chloride 9 mg/ml (0.9%) solution for injection because it has been demonstrated that chloride reduces the solubility of Methylthioninium Chloride.
More than 30 neurodegenerative diseases including Alzheimer disease (AD), frontotemporal lobe dementia (FTD), and some forms of Parkinson disease (PD) are characterized by the accumulation of an aggregated form of the microtubule-binding protein tau in neurites and as intracellular lesions called neurofibrillary tangles. Diseases with abnormal tau as part of the pathology are collectively known as the tauopathies. Methylthioninium chloride, also known as methylene blue (MB), has been shown to reduce tau levels in vitro and in vivo and several different mechanisms of action have been proposed. Herein we demonstrate that autophagy is a novel mechanism by which MB can reduce tau levels. Incubation with nanomolar concentrations of MB was sufficient to significantly reduce levels of tau both in organotypic brain slice cultures from a mouse model of FTD, and in cell models. Concomitantly, MB treatment altered the levels of LC3-II, cathepsin D, BECN1, and p62 suggesting that it was a potent inducer of autophagy. Further analysis of the signaling pathways induced by MB suggested a mode of action similar to rapamycin. Results were recapitulated in a transgenic mouse model of tauopathy administered MB orally at three different doses for two weeks. These data support the use of this drug as a therapeutic agent in neurodegenerative diseases.
Methylthioninium chloride, commonly called methylene blue, is a salt used as a dye and as a medication. Methylene blue is a thiazine dye. As a medication, it is mainly used to treat methemoglobinemia by converting/chemically reducing the ferric iron in hemoglobin to ferrous iron. Specifically, it is used to treat methemoglobin levels that are greater than 30% or in which there are symptoms despite oxygen therapy. It has previously been used for treating cyanide poisoning and urinary tract infections, but this use is no longer recommended.
Methylthioninium chloride (formerly called methylene blue) is approved for the management of drug-induced methaemoglobinaemia in adults. It is also used for other purposes, but these uses are not covered by the product licence.
On the basis of 27 reports of CNS toxicity associated with methylthioninium, the January 2008 issue of drug safety update advised how the risk could be minimised. The summary of product characteristics for methylthioninium chloride has now been updated to mention the possibility of CNS toxicity in patients being treated with serotonergic drugs such as selective serotonin reuptake inhibitor (SSRI) antidepressants, clomipramine, and venlafaxine. Features of toxicity include confusion, disorientation, agitation, expressive aphasia, altered muscle tone in limbs, hypoxia, ocular symptoms, and depressed level of consciousness.
All cases reviewed described CNS toxicity after the use of methylthioninium as a visualising agent in parathyroid or thyroid surgery. Since the review, further cases of CNS toxicity in association with methylthioninium have come to light. Five of the new cases involved parathyroid surgery (2 cases reported to us on Yellow Cards and 3 documented in the literature[footnote 1] [footnote 2] [footnote 3]). However, a further new case of CNS toxicity involved the use of methylthioninium for management of uncontrollable hypotension during cardiac surgery [footnote 4].
The cholinergic system is involved in cognition as well as in age-related cognitive decline and Alzheimer disease (AD). Cholinergic enhancers ameliorate AD symptoms and represent the main current therapy for AD. MTC (Methylthioninium chloride), an antioxidant with metabolism-enhancing properties may be a novel candidate with pro-cognitive capacities. 041b061a72