TISSUEBLUE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TISSUEBLUE (TISSUEBLUE).

How it works

Tissueblue (methylene blue) acts as a redox agent that accepts electrons from NADPH via the enzyme NADPH-methemoglobin reductase, converting methemoglobin (Fe3+) to hemoglobin (Fe2+). It also inhibits the enzyme guanylyl cyclase, reducing cyclic GMP levels and thereby causing vasoconstriction in distributive shock.

What the body does with it

Metabolism	Primarily reduced to leukomethylene blue by NADPH-dependent reductases in erythrocytes and other tissues. Renal excretion of unchanged drug and metabolites.
Excretion	Primarily renal excretion of unchanged dye (approx. 97% within 48 hours); minimal biliary/fecal elimination (<3%).
Half-life	Terminal elimination half-life is approximately 4-6 hours in patients with normal renal function. Half-life is prolonged in renal impairment.
Protein binding	Primarily binds to albumin; approximately 80-90% protein-bound.
Volume of Distribution	Approximately 0.1-0.3 L/kg, indicating distribution primarily within the intravascular space.
Bioavailability	Not applicable for oral route; only administered intravenously or intradermally. Bioavailability is 100% after IV administration.
Onset of Action	Within seconds to minutes after intravenous injection; visualization of lymphatic vessels occurs immediately.
Duration of Action	Staining of lymphatic vessels persists for 30-60 minutes; residual staining may last up to 24 hours in tissues.

Classification & Brands

Dosing & administration

0.1-0.3 mg/kg intravenous bolus over 1-2 minutes, may repeat once after 30 minutes if needed; maximum single dose 20 mg.

Dosage form	SOLUTION
Renal impairment	No dose adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min, reduce dose by 50% and monitor for accumulation.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: avoid use or use with extreme caution due to risk of encephalopathy.
Pediatric use	0.1-0.2 mg/kg intravenous bolus, maximum 5 mg per dose; may repeat once after 30 minutes. Not recommended for neonates.
Geriatric use	Start at 0.05 mg/kg intravenous, maximum 10 mg per dose; titrate cautiously due to increased sensitivity and risk of hypotension.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for TISSUEBLUE (TISSUEBLUE).

Breastfeeding	It is unknown if TissueBlue is excreted in human milk. Due to the potential for serious adverse reactions in nursing infants, breastfeeding should be discontinued during treatment and for at least 5 days after the last dose. M/P ratio not available.
Teratogenic Risk	TissueBlue is not recommended during pregnancy due to potential fetal toxicity. In the first trimester, there is a risk of teratogenicity based on animal studies. In the second and third trimesters, there is a risk of fetal harm, including skeletal abnormalities and reduced fetal weight. Use only if clearly needed and benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

WARNING: SEROTONIN SYNDROME WITH CONCOMITANT USE OF SEROTONERGIC DRUGS — Tissueblue is a potent inhibitor of monoamine oxidase A (MAO-A). Concomitant use with serotonergic drugs (e.g., SSRIs, SNRIs, MAOIs) may cause life-threatening serotonin syndrome. Avoid use in patients taking serotonergic agents unless the benefit outweighs the risk.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Patients with severe renal impairment (eGFR <30 mL/min) due to accumulation risk.","Concomitant use with serotonergic drugs (e.g., SSRIs, SNRIs, MAOIs) unless no alternative.","G6PD deficiency (risk of hemolytic anemia).","Known hypersensitivity to methylene blue or thiazine dyes.","Pregnancy (may cause hemolytic anemia in fetus, especially in G6PD-deficient mothers)."]

Clinical Precautions

Precautions

["Risk of serotonin syndrome with serotonergic drugs; monitor for symptoms (agitation, hyperthermia, clonus, diaphoresis).","May cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.","Intra-arterial injection may cause severe vasoconstriction and tissue necrosis.","False lowering of pulse oximetry readings due to absorption of light at similar wavelengths.","May interfere with laboratory tests (e.g., bilirubin, hemoglobin).","Use with caution in renal impairment."]

Clinical Tips & Counseling

Drug interactions

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TISSUEBLUE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TISSUEBLUE (TISSUEBLUE).

How it works

What the body does with it

Metabolism	Primarily reduced to leukomethylene blue by NADPH-dependent reductases in erythrocytes and other tissues. Renal excretion of unchanged drug and metabolites.
Excretion	Primarily renal excretion of unchanged dye (approx. 97% within 48 hours); minimal biliary/fecal elimination (<3%).
Half-life	Terminal elimination half-life is approximately 4-6 hours in patients with normal renal function. Half-life is prolonged in renal impairment.
Protein binding	Primarily binds to albumin; approximately 80-90% protein-bound.
Volume of Distribution	Approximately 0.1-0.3 L/kg, indicating distribution primarily within the intravascular space.
Bioavailability	Not applicable for oral route; only administered intravenously or intradermally. Bioavailability is 100% after IV administration.
Onset of Action	Within seconds to minutes after intravenous injection; visualization of lymphatic vessels occurs immediately.
Duration of Action	Staining of lymphatic vessels persists for 30-60 minutes; residual staining may last up to 24 hours in tissues.

Classification & Brands

Dosing & administration

0.1-0.3 mg/kg intravenous bolus over 1-2 minutes, may repeat once after 30 minutes if needed; maximum single dose 20 mg.

Dosage form	SOLUTION
Renal impairment	No dose adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min, reduce dose by 50% and monitor for accumulation.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: avoid use or use with extreme caution due to risk of encephalopathy.
Pediatric use	0.1-0.2 mg/kg intravenous bolus, maximum 5 mg per dose; may repeat once after 30 minutes. Not recommended for neonates.
Geriatric use	Start at 0.05 mg/kg intravenous, maximum 10 mg per dose; titrate cautiously due to increased sensitivity and risk of hypotension.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for TISSUEBLUE (TISSUEBLUE).

Breastfeeding	It is unknown if TissueBlue is excreted in human milk. Due to the potential for serious adverse reactions in nursing infants, breastfeeding should be discontinued during treatment and for at least 5 days after the last dose. M/P ratio not available.
Teratogenic Risk	TissueBlue is not recommended during pregnancy due to potential fetal toxicity. In the first trimester, there is a risk of teratogenicity based on animal studies. In the second and third trimesters, there is a risk of fetal harm, including skeletal abnormalities and reduced fetal weight. Use only if clearly needed and benefit outweighs risk.