Methylene Blue
Methylthioninium chloride
Also known as: Azul Metile · Collubleu · Desmoidpillen · Vitableu · Urolene Blue · Zumetil · Methylene Blue · Proveblue · Methylthioninium chloride · Azul de metileno · Blu di metilene · CI basic blue 9 · Colour index no. 52015 · Methylenii caeruleum · Methylthioninii chloridum · Schultz no. 1038 · Tetramethylthionine chloride trihydrate
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Audited v13 dosing evidence
Reviewed non-calculator evidenceReviewed non-calculator evidence (1)
Evidence only — not for automatic calculation
Nitrite and nitrate toxicoses
TABLE 128.6. Agent: Methylene blue. Dosage: 2 mg/mL bath to effect52. Species/Comments: Nitrite and nitrate toxicoses.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Methylene blue is a thiazine dye primarily used as an antidote for treating methemoglobinemia in ruminants, typically secondary to oxidative agents like nitrates or chlorates. It is also occasionally employed as an adjunctive or alternative therapy for cyanide toxicity.
In small animal medicine, it is uniquely utilized as an intra-operative intravenous stain to preferentially identify islet-cell tumors (insulinomas) of the pancreas in dogs, aiding in their surgical removal.
Clinical Pearls:
- Methylene blue has a paradoxical dose-dependent effect: at low doses, it acts as a reducing agent to treat methemoglobinemia, but at high doses, it acts as an oxidizing agent and can cause methemoglobinemia.
- Cats are exquisitely sensitive to oxidative damage from this drug, making its use highly controversial and generally contraindicated in feline patients.
Mechanism of action
Methylene blue acts as an artificial electron acceptor and donor in red blood cells.
- Reduction Pathway: In the tissues, methylene blue interacts with the enzyme NADPH-methemoglobin reductase. It is rapidly reduced to leucomethylene blue.
- Hemoglobin Conversion: Leucomethylene blue serves as a reducing agent (electron donor) → converts methemoglobin (Fe3+) back to functional oxygen-carrying hemoglobin (Fe2+).
- Oxidation Pathway (High Doses): Methylene blue is inherently an oxidizing agent. If administered at high doses (species dependent), it overwhelms the reduction pathway and directly oxidizes hemoglobin → causes methemoglobinemia.
Safety & warnings
Contraindications
- Cats (considered contraindicated by most clinicians due to severe sensitivity)
- Renal insufficiency
- Hypersensitivity to methylene blue
- Intraspinal (intrathecal) injection
- Lactating dairy animals
- Severe renal impairment
- Patients with G6PD deficiency (can cause severe hemolysis)
- Use with extreme caution in cats due to high susceptibility to Heinz body formation
Adverse effects
- Red cell morphological changes
- Decreased red blood cell life span
- Necrotic abscesses (if injected SC or extravasated IV)
- Green-blue discoloration of urine
- Heinz body anemia (especially in cats)
- Paradoxical methemoglobinemia (at high doses)
- Tissue necrosis (if extravasated)
- Blue/green discoloration of urine, feces, and mucous membranes
- Nausea and vomiting
Precautions
WARNING: Cats are highly sensitive to methylene blue and can rapidly develop Heinz body anemia and methemoglobinemia. Dogs and horses can also develop these effects at relatively low dosages.
- Administration: Must be given IV. Extravasation or subcutaneous injection can cause severe necrotic abscesses.
- Efficacy: Considered relatively ineffective in reducing methemoglobin in horses.
- Food Animal Residues: FARAD recommends a minimum milk withdrawal time of 4 days. Meat withdrawal is conservatively recommended at 180 days due to carcinogenicity concerns, though some data suggest 14 days may be sufficient.
- Pregnancy: FDA Category C. Safe use during pregnancy has not been demonstrated.
Drug interactions
Methylene blue is a potent reversible monoamine oxidase inhibitor (MAOI); concurrent use can precipitate fatal serotonin syndrome.
Increased risk of serotonin toxicity.
Monitoring
- Methemoglobinemia levels
- Red cell morphology
- Red cell indices
- Hematocrit
- Methemoglobin levels
- Complete Blood Count (CBC) for Heinz bodies and hemolysis
- Arterial blood gas (ABG)
- Renal function
- Signs of serotonin syndrome if on concurrent serotonergic drugs
Pharmacokinetics
Half-life
Absorption
Absorbed from the GI tract, but is usually administered parenterally in veterinary medicine.
Distribution
Rapidly converted to leucomethylene blue in tissues.
Metabolism
Converted to leucomethylene blue, which serves as the active reducing agent.
Elimination
Excreted in the urine and bile, primarily in the colorless form, but some unchanged drug may also be excreted.
Overdose
The LD50 for IV administered 3% methylene blue is approximately 43 mg/kg in sheep. High doses can paradoxically cause methemoglobinemia due to the drug's inherent oxidizing properties.
Available products
Formulations
- 1% (10 mg/mL) solution
- Powder for compounding
- Injectable: 10 mg/ml (1% solution)
Veterinary
- 1% (10 mg/mL) methylene blue solution (Centaur) - labeled as a dye, laboratory indicator, and reagent
- Methylene Blue, USP powder
Human-labeled
- Methylene Blue Injection: 10 mg/mL in 1 mL & 10 mL ampules
- Methylthioninium chloride 10 mg/ml (1%) injection (e.g., Proveblue)
Regulatory status
POM (Prescription Only Medicine)
POM (Prescription Only Medicine)
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store at room temperature unless otherwise instructed by the manufacturer. Physically incompatible when mixed with caustic alkalies, dichromates, iodides, and oxidizing or reducing agents.
Client information
- Professional Supervision: Because of the potential toxicity of this agent and the seriousness of methemoglobin-related intoxications, this drug should be used with close professional supervision only.
- Staining: Methylene blue may severely stain clothing or skin. Removal may be accomplished using hypochlorite solutions (bleach).
- Urine Color: Pet owners should be aware that the animal's urine may turn a green-blue color during treatment.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.