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Antidotes & Toxicology Pregnancy: US labelling: methylene blue may cause fetal harm when administered to a pregnant woman; intra-amniotic injection of a methylene blue class product in the second trimester was associated with neonatal intestinal atresia and fetal death, and intra-amniotic injection hours to days before birth can result in hyperbilirubinaemia, haemolytic anaemia, skin staining, methaemoglobinaemia, respiratory distress and photosensitivity in the newborn (observe the newborn after administration to a pregnant woman at term). Adverse developmental outcomes occurred in rats and rabbits given oral methylene blue during organogenesis. Only use during pregnancy if the potential benefit justifies the potential risk to the fetus. Lactation: there is no information on the presence of methylene blue in human milk; discontinue breast-feeding during and for up to 8 days after treatment.

Methylene Blue

Brand names: ProvayBlue, Methylene Blue Injection

Methylene blue (methylthioninium chloride) is a thiazine dye used as the first-line antidote for acquired methaemoglobinaemia and, in some settings, for refractory vasoplegic shock.

Adult dose

Dose: Acquired methaemoglobinaemia: 1 mg/kg intravenously over 5-30 minutes
Route: Intravenous (do not administer subcutaneously)
Frequency: Single dose; if the methaemoglobin level remains greater than 30% or clinical signs and symptoms persist, a repeat dose of up to 1 mg/kg may be given one hour after the first dose
The US label covers acquired methaemoglobinaemia only; it gives no dose for any other use. Ensure patent venous access before administration. The injection is hypotonic and may be diluted before use in 50 mL 5% Dextrose Injection to avoid local pain, particularly in the paediatric population; use the diluted solution immediately after preparation. Avoid diluting with sodium chloride solutions because chloride reduces the solubility of methylene blue. Presentation: 50 mg/10 mL (5 mg/mL; 0.5%) single-dose vials. If methaemoglobinaemia does not resolve after 2 doses, consider initiating alternative interventions. Methaemoglobinaemia may not resolve or may rebound after response in patients with methaemoglobinaemia due to aryl amines such as aniline or sulfa drugs such as dapsone, and methylene blue may not be effective in G6PD deficiency. Use the lowest effective number of doses. Boxed warning: serious or fatal serotonin syndrome with serotonergic drugs and opioids. The US label's indication and 1 mg/kg regimen cover paediatric as well as adult patients but no separate paediatric regimen is printed - for children use a children's formulary. No UK SPC for methylene blue injection is listed on eMC — this dose is from US prescribing information (Methylene Blue injection, 0.5%, XIROMED, LLC) and must be verified against UK practice.

Dose adjustments

Renal

Moderate or severe renal impairment (eGFR 15-59 mL/min/1.73 m2): a single dose of 1 mg/kg. If the methaemoglobin level remains greater than 30% or clinical symptoms persist 1 hour after dosing, consider initiating alternative interventions for the treatment of methaemoglobinaemia.

Hepatic

Hepatic impairment: monitor patients longer for toxicity and drug interactions due to delayed clearance.

Dose independently re-sourced from US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • Severe hypersensitivity reactions to methylene blue or any other thiazine dye (including anaphylaxis or other severe hypersensitivity to a methylene blue class product in the past)
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency, due to the risk of haemolytic anaemia (and it may not be reduced to its active form in vivo)

Side effects

  • Headache, hypokalaemia, diarrhoea, hypomagnesaemia, myoclonus, nausea and seizure-like phenomena (adverse reactions of 2% or more in adults)
  • Serotonin syndrome with concomitant serotonergic drugs and opioids - serious or fatal cases reported
  • Anaphylactic reactions to methylene blue class products
  • Haemolytic anaemia - onset may be delayed 1 or more days after treatment (Heinz bodies, raised indirect bilirubin, low haptoglobin, negative Coombs test); may require red blood cell transfusion
  • Confusion, dizziness and disturbances in vision
  • Methylene blue is a blue dye that passes freely into the urine

Interactions

  • Serotonergic drugs and opioids - avoid concomitant use (SSRIs, SNRIs, MAOIs, bupropion, buspirone, clomipramine, mirtazapine, linezolid, opioids, dextromethorphan): risk of serious CNS reactions including potentially fatal serotonin syndrome; methylene blue is a potent reversible inhibitor of monoamine oxidase
  • If intravenous use cannot be avoided in patients taking serotonergic medicines, choose the lowest possible dose and observe the patient closely for CNS effects for up to 4 hours after administration
  • Patients should be advised not to take serotonergic drugs within 72 hours after the last dose

Monitoring

  • Methaemoglobin level: repeat dosing is guided by a level that remains above 30%; monitor response through resolution of methaemoglobinaemia, and consider other options if no response after 2 doses or if it rebounds
  • Pulse oximetry may underestimate oxygen saturation - obtain an arterial blood sample for an alternative method if oxygen saturation is needed during or shortly after infusion
  • Bispectral Index (BIS) may fall after administration - use alternative methods to assess the depth of anaesthesia if given during surgery
  • Monitor for emergence of serotonin syndrome; if symptoms occur, discontinue and initiate supportive treatment
  • Monitor for anaphylaxis (angioedema, urticaria, bronchospasm); discontinue and initiate supportive treatment if it occurs
  • Monitor for haemolysis (delayed onset possible); discontinue and consider alternative treatments if severe haemolysis occurs
  • Methylene blue may interfere with urine tests that rely on a blue indicator (e.g. leucocyte esterase dipstick)
  • Advise patients to refrain from driving or operating machinery until confusion, dizziness and visual disturbances have resolved

Clinical monograph

How it works

It acts as an electron-transfer cofactor for NADPH-methaemoglobin reductase, reducing the ferric iron of methaemoglobin back to the functional ferrous form so haemoglobin can again carry oxygen.

Prescribing in practice

  • Avoid in patients taking serotonergic drugs where possible, as methylene blue has potent monoamine oxidase inhibitory activity and can precipitate serotonin syndrome.
  • It is contraindicated or used with extreme caution in G6PD deficiency, where it is ineffective and may itself cause haemolysis.
  • Give by slow intravenous injection; rapid or excessive administration can paradoxically worsen methaemoglobinaemia.

Monitoring

Monitor methaemoglobin levels, oxygen saturation (noting pulse oximetry is unreliable in methaemoglobinaemia, so co-oximetry is preferred) and clinical response after administration.

Counselling the patient

  • Warn the patient that urine, saliva and the skin may turn blue-green for a day or two.
  • Advise the patient to report new agitation, fever or muscle twitching, which could indicate serotonin syndrome.
  • Explain the treatment reverses the abnormal blood pigment causing breathlessness or blue discolouration.

Evidence & guidelines

Methylene blue is established as the standard antidote for symptomatic acquired methaemoglobinaemia, with the MHRA having highlighted the serotonin syndrome interaction risk.

Reference: NPIS Toxbase; MHRA DSU 2008 (serotonin syndrome); BMJ 2011; 342:d3076; Anaesthesia 2015; 70(10):1142-1153; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

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