Pharmacology · Specific antidotes
Methylthioninium chloride (methylene blue) !
A blue dye that turns methaemoglobin back into normal haemoglobin. It is avoided in G6PD deficiency and with serotonergic drugs.
Updated 2026-11-01
Also called: Methylene blue
Mechanism of action
In methaemoglobinaemia the haem iron is oxidised to the ferric (Fe³⁺) state and cannot carry oxygen. Inside red cells, an NADPH-dependent reductase converts methylene blue to leucomethylene blue, which reduces the iron back to the ferrous (Fe²⁺) state. Because the pathway needs NADPH from the pentose phosphate pathway, it fails, and can cause haemolysis, in G6PD deficiency. Methylene blue is also a potent inhibitor of monoamine oxidase.
- An oxidant turns haem Fe²⁺ into Fe³⁺: methaemoglobin
- NADPH reductase turns methylene blue into leucomethylene blue
- Leucomethylene blue reduces Fe³⁺ back to Fe²⁺
- Haemoglobin carries oxygen again; cyanosis fades
Pharmacokinetics
- Metabolism
- Mainly conjugated by UGT enzymes in the liver; minor cytochrome P450 metabolism
- Elimination
- In urine and stool, which turn blue-green
- Half-life
- About 24 hours
- Onset and duration
- The peak effect usually comes within 30 minutes
Indications
- Symptomatic acquired methaemoglobinaemia, for example from sodium nitroprusside or benzocaine (including benzocaine used to adulterate street drugs) Methemoglobinemia →
Adverse effects
Common
- Blue-green urine and stools, bluish skin
- Headache
- Nausea, abdominal pain and diarrhoea
- Low potassium and magnesium
- Pain or irritation at the infusion site
Contraindications
- G6PD deficiency (risk of haemolysis, and the drug may not work)
- Severe hypersensitivity to methylene blue or other thiazine dyes
Key interactions
- SSRIs, SNRIs, MAO inhibitors and opioids
- Serious or fatal serotonin syndrome, because methylene blue inhibits monoamine oxidase
- Pulse oximetry and blue-indicator urine tests
- The dye causes falsely low saturation readings and can distort dipstick results
What is monitored
- Methaemoglobin level by co-oximetry on a blood gas sample
- Haemoglobin and signs of haemolysis
- Neurological status and signs of serotonin toxicity
Administration and safety
- Slow intravenous infusion through a patent vein; never subcutaneously
- Diluted in 5% dextrose; sodium chloride is avoided because chloride reduces its solubility
- A second dose may follow after about an hour if methaemoglobinaemia persists; if two doses fail, other treatments are considered
- In Colombia it is registered as a diagnostic agent, not as an antidote, which can limit access
Nursing care
- Ask about G6PD deficiency and serotonergic medicines before it is given
- Do not rely on pulse oximetry; use arterial co-oximetry
- Check the infusion site
- Tell the patient that urine and stools will turn blue-green
Pregnancy and breastfeeding
It may cause fetal harm and is generally not recommended in pregnancy or breastfeeding unless the methaemoglobinaemia is life-threatening.
Test yourself
Think of the answer, then tap the question to see it.
How does methylene blue reduce methaemoglobin?
An NADPH-dependent reductase converts it to leucomethylene blue, which reduces Fe³⁺ back to Fe²⁺.
Why is methylene blue contraindicated in G6PD deficiency?
These patients lack NADPH, so it may not work and can trigger haemolysis.
Which drug combination with methylene blue can cause serotonin syndrome?
SSRIs, SNRIs, MAO inhibitors and opioids, because methylene blue inhibits monoamine oxidase.
Why is pulse oximetry unreliable during treatment?
The blue dye interferes with the reading and underestimates saturation; co-oximetry is used.
Related drugs
Related conditions
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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - METHYLENE BLUE injection (DailyMed (U.S. National Library of Medicine), 2026); Guía para el Manejo de Emergencias Toxicológicas (Ministerio de Salud y Protección Social; Organización Panamericana de la Salud, 2017); eEML - Electronic Essential Medicines List (World Health Organization, 2025); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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