Methylthioninium chloride

Full Prescribing Info
Dosage/Direction for Use

Acute methaemoglobinaemia
Adult: Dilute 10-20 mL of 0.5% solution for inj with 100-200 mL water for inj.
May be diluted with 50 mL of 5% dextrose in water prior to administration.
Incompatibility: Reduced solubility with 0.9% NaCl solution for inj.

Acute methaemoglobinaemia
Adult: As 0.5% or 1% solution: 1-2 mg/kg via slow inj over a period of 5 minutes, may be repeated after 30-60 minutes if necessary. Max total dose: 7 mg/kg per treatment course; 4 mg/kg per treatment course (aniline- or dapsone-induced methaemoglobinaemia).
Child: As 0.5% solution: Newborn to 3 months infants
0.3-0.5 mg/kg via slow inj over 5 minutes, may be repeated after 60 minutes if necessary. >3 months Same as adult dose.
Reconstitution: May be diluted with 50 mL of 5% dextrose in water prior to administration.
Incompatibility: Reduced solubility with 0.9% NaCl solution for inj.

Special Populations: Pharmacogenomics: G6PD deficiency is an X-linked genetic variant wherein women may either be homozygous or heterozygous for the variant, while men may be hemizygous. Based on studies, several cases of haemolytic anaemia were reported in individuals of various ethnicities after exposure to IV methylthioninium chloride. Most, but not all, were tested and identified to be G6PD deficient. Drug labels (as approved by FDA, EMA and PMDA) for methylthioninium chloride states that it is contraindicated in patients with G6PD deficiency due to the risk of haemolytic anaemia. Methylthioninium chloride may be ineffective for the treatment of methaemoglobinaemia in G6PD deficient patients due to their inability to reduce the drug to its active form. Furthermore, EMA and PMDA approved drug labels also states that methylthioninium chloride is contraindicated in patients with a deficiency in NADPH reductase (encoded by BLVRB gene). Individuals who failed to respond to methylthioninium chloride may indicate a deficiency in cytochrome b5 reductase (CYPB5R3) or G6PD. Consider alternative treatment options.
Hypersensitivity to methylthioninium chloride or other thiazine dyes. G6PD deficiency, NADPH reductase deficiency, nitrite-induced methaemoglobinaemia during treatment of cyanide poisoning, chlorate-induced methaemoglobinaemia. Pregnancy and lactation.
Special Precautions
Patients with hyperglycaemia or diabetes mellitus. Not intended to be administered via SC or intraspinal inj. Hepatic and renal impairment. Children; newborn and infants (<3 months). Patient Counselling This drug may cause dizziness, confusion, or visual disturbances, if affected, do not drive or operate machinery. Monitoring Parameters Monitor arterial blood gases, CBC, methaemoglobin levels (via co-oximeter), transcutaneous oxygen saturation, renal function, ECG, blood pressure.
Adverse Reactions
Significant: Hypersensitivity; haemolytic anaemia, methaemoglobinaemia (at high doses or in G6PD deficient patients), CNS depression, cutaneous photosensitivity reaction, skin and body fluid discolouration (blue: skin, blue green: urine, faeces). Cardiac disorders: Chest pain, tachycardia, cardiac arrhythmia. Eye disorders: Mydriasis. Gastrointestinal disorders: Nausea, vomiting, abdominal pain, dysgeusia. General disorders and administration site conditions: Inj site pain or necrosis, fever. Investigations: Hb decreased. Metabolism and nutrition disorders: Hyperbilirubinaemia. Musculoskeletal and connective tissue disorders: Pain in extremity. Nervous system disorders: Dizziness, headache, paraesthesia, tremor. Psychiatric disorders: Anxiety, confusional state, agitation, aphasia. Respiratory, thoracic and mediastinal disorders: Dyspnoea, tachypnoea. Skin and subcutaneous tissue disorders: Hyperhidrosis. Vascular disorders: Hypertension, hypotension.
Potentially Fatal: Serotonin syndrome (in combination with serotonergic drugs).
Symptoms: Patients without methaemoglobinaemia: Nausea, vomiting, chest pain, tachycardia, apprehension, severe sweating, tremor, mydriasis; skin, mucous membrane and urine discolouration (blue-green), abdominal pain, dizziness, paraesthesia, headache, confusion, hypertension, ECG changes (T wave flattening or inversion), and mild methaemoglobinaemia. Patients with methaemoglobinaemia: Dyspnoea, tachypnoea, chest pain, tremor, cyanosis, and haemolytic anaemia. Management: Symptomatic and supportive treatment.
Drug Interactions
May increase plasma concentrations of sensitive CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 substrates. May transiently increase exposure of cimetidine, metformin, aciclovir.
Potentially Fatal: Increased risk of serotonin syndrome with SSRIs, serotonin and norepinephrine reuptake inhibitors (SNRIs), MAOIs, bupropion, buspirone, clomipramine, mirtazapine.
Lab Interference
May result to underestimation of the oxygen saturation reading in pulse oximetry. May cause false-positive result in phenolsulfonphthalein excretion test. May interfere with the bispectral index values and in the interpretation of urine tests relying on blue indicator (e.g. dipstick for leucocyte esterase).
Methylthioninium chloride, a thiazine dye and oxidation-reduction agent, accelerates the conversion of methaemoglobin to haemoglobin (Hb) in low concentrations. In situ, nicotinamide adenine dinucleotide phosphate (NADPH) reductase converts the methylthioninium chloride into leucomethylthioninium chloride which then reduces the ferric iron of methaemoglobin to the ferrous state of the normal Hb. Synonym: Methylene blue
Onset: Reduction of methaemoglobin: 30-60 minutes (IV).
Absorption: Well absorbed from the gastrointestinal tract. Time to peak plasma concentration: Approx 1-2 hours (oral); 30 minutes (IV).
Distribution: Extensively distributed in the tissues. Volume of distribution 255 L (±58 L). Plasma protein binding: 94%.
Metabolism: Undergoes first-pass metabolism or distribution in the tissues via peripheral reduction to form leucomethylene blue.
Excretion: Mainly via urine as leucomethylene blue, with small proportion as unchanged drug; bile. Elimination half-life: Approx 5-6.5 hours.
Intravenous: Store between 20-25°C. Do not refrigerate or freeze. Protect from light. Oral: Store between 20-25°C. Do not refrigerate or freeze. Protect from light.
ATC Classification
V03AB17 - methylthioninium chloride ; Belongs to the class of antidotes. Used in the management of prilocaine overdose.
V04CG05 - methylthioninium chloride ; Belongs to the class of diagnostic agents used to determine gastric secretion.
Disclaimer: This information is independently developed by CIMS based on methylthioninium chloride from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to CIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, CIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 CIMS. All rights reserved. Powered by
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