Lumeblue (Previously Methylthioninium Chloride Cosmo)

Posology Adults including the elderly (≥ 65 years) The recommended total dose is 200 mg methylthioninium chloride, corresponding to eight 25 mg tablets. g. g. 4 L) polyethylene glycol (PEG) based bowel cleansing preparation and should be completed the evening prior to the colonoscopy to ensure there is enough time for the tablets to reach the colon and locally release the methylthioninium chloride prior to the colonoscopy.

2). Renal impairment No dose adjustment is required in patients with mild renal impairment. 2). 3 Hepatic impairment No dose adjustment is required in patients with mild or moderate hepatic impairment. 2). Paediatric population The safety and efficacy of the medicinal product in children aged less than 18 years have not been established.

No data are available. Method of administration For oral use. Tablets should be swallowed whole, without crushing, breaking or chewing. The tablets are coated with a gastro-resistant film that facilitates the delivery of the dye into the colon.

Breaking the gastro- resistant film by crushing or chewing the tablets may cause early release of the dye in the upper part of the gastrointestinal tract, with a possible loss of the treatment effectiveness. g. g. 4 L) PEG based bowel cleansing regimen chosen by the healthcare provider according to the dosing schedule below: • The first dose of 3 tablets should be taken after drinking at least 1 L of the bowel cleansing preparation; • The second dose of 3 tablets should be taken 1 hour after the first dose; • The last dose of 2 tablets should be taken 1 hour after the second dose.

Tablets should be taken orally with the bowel cleansing preparation chosen by the healthcare provider or with equivalent water volumes and the proposed dosing schedule is compatible with either full dose or split dose bowel preparations.

4%), which gradually diminish over the following days. It is associated with transient nausea and vomiting. Tabulated list of adverse reactions Adverse reactions are classified according to the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), very rare (< 1/10 000), or not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. Data presented below are based upon clinical studies conducted with Lumeblue. All adverse reactions recorded at a frequency greater than placebo are reported.

Additionally, adverse drug reactions of known frequency, reported with methylthioninium chloride administered intravenously in the treatment of methaemoglobinaemia are included in the following table. 5) Not known Vascular disorders Hypotension Uncommon Respiratory, thoracic and mediastinal disorders Cough Uncommon Nasal congestion Uncommon Rhinorrhoea Uncommon Gastrointestinal disorders Faeces discoloured Very common Abdominal pain Common Vomitingc Common Nauseac Common Haematemesis Uncommon 7 System organ class Adverse reaction Frequency Diarrhoea Uncommon Abdominal discomfort Uncommon Skin and subcutaneous tissue disorders Skin discolouration (blue)b,c Very common Sweatingb Very common Ecchymosis Uncommon Night sweats Uncommon Pruritus Uncommon Rash Uncommon Telangiectasia Uncommon Photosensitivity Not known Musculoskeletal and connective tissue disorders Pain in extremityb Very common Flank pain Uncommon Renal and urinary disorders Chromaturia Very common Polyuria Uncommon Dysuria Uncommon General disorders and administration site conditions Chest painb Common Pain Uncommon Chills Uncommon Injury, poisoning and procedural complications Procedural nausea Uncommon a The inclusion of anaphylactic reactions reported in the table is reflective of sporadic and spontaneous reporting in literature.

No event of anaphylactic reaction has been identified during clinical studies of Lumeblue. b These terms are included as they were reported as very common or common in clinical studies with methylthioninium chloride via intravenous administration.

c See section below: Description of specific adverse reactions for more detail. Description of specific adverse reactions Frequent adverse reactions In the pooled safety data from the clinical program, the most common related TEAE were chromaturia and discoloured faeces, as described above.

4). Serotonin syndrome Serotonin syndrome has been reported with the use of methylthioninium chloride when administered via the intravenous use in combination with serotonergic medicinal products. Patients treated with methylthioninium chloride in combination with serotonergic medicinal products should be monitored for the emergence of serotonin syndrome.

5). Nausea and vomiting Nausea and vomiting are well recognised adverse reactions associated with the use of PEG-based bowel cleansing preparations, however in clinical studies, patients were more likely to experience nausea and vomiting when receiving Lumeblue in combination with a bowel preparation agent, than when receiving the bowel preparation alone.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

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Serotonin syndrome Serotonin syndrome has been reported with the use of methylthioninium chloride when administered intravenously in combination with serotonergic medicinal products. It is not known if there is a risk of serotonin syndrome when methylthioninium chloride is administered orally in preparation for colonoscopy.

Patients treated with methylthioninium chloride in combination with serotonergic medicinal products should be monitored for the emergence of serotonin syndrome. 5). Photosensitivity 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.

Patients should be advised to take protective measures against exposure to light, because 4 photosensitivity may occur after administration of methylthioninium chloride. General colouration Methylthioninium chloride imparts a blue-green colour to urine, faeces and a blue colour to skin which may hinder a diagnosis of cyanosis.

Interference with in vivo monitoring devices Inaccurate pulse oximeter readings The presence of methylthioninium chloride in the blood may result in an underestimation of the oxygen saturation reading by pulse oximetry. If a measure of oxygen saturation is required after administration of the medicinal product, it is advisable to check oxygen saturation by CO-oximetry when available.

Bispectral index monitor A fall in the bispectral index (BIS) has been reported following administration of methylthioninium chloride class products. If Lumeblue is administered during surgery, alternative methods for assessing the depth of anaesthesia should be employed.

Excipient warning This medicinal product contains soya lecithin. 3).

6).