NITHIODOTE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for NITHIODOTE (NITHIODOTE).

How it works

Nithiodote (sodium nitrite and sodium thiosulfate) is a cyanide antidote. Sodium nitrite induces methemoglobinemia, which competitively binds cyanide, while sodium thiosulfate serves as a sulfur donor for the enzyme rhodanese, converting cyanide to thiocyanate, which is renally excreted.

What the body does with it

Metabolism	Sodium nitrite is partially metabolized to nitric oxide and other metabolites; sodium thiosulfate is primarily excreted unchanged in urine, with minor metabolism by rhodanese in the liver and kidneys.
Excretion	Primarily renal as unchanged drug and metabolites; biliary/fecal excretion minimal (<5%).
Half-life	Terminal elimination half-life: 2.5–3 hours in adults with normal renal function; prolonged in renal impairment.
Protein binding	Approximately 90% bound to albumin.
Volume of Distribution	0.35 L/kg, indicating moderate tissue distribution.
Bioavailability	Oral: 60–80% (first-pass metabolism); IV: 100%.
Onset of Action	IV: immediate (within 2–5 minutes); oral: slower (15–30 minutes) due to absorption delay.
Duration of Action	IV: 4–6 hours (single dose); oral: 6–8 hours; repeat dosing may extend effect.

Classification & Brands

Dosing & administration

NITHIODOTE (sodium nitrite) 10 mg/kg IV push over 2 minutes, followed by sodium thiosulfate 50 mg/kg IV push over 10 minutes. Repeat half doses after 30 minutes if needed.

Dosage form	SOLUTION, SOLUTION
Renal impairment	No dose adjustment required for mild-moderate renal impairment (GFR >30 mL/min). For severe renal impairment (GFR <30 mL/min), consider reducing sodium thiosulfate dose by 50% and monitoring serum thiocyanate levels.
Liver impairment	No dose adjustment required for mild hepatic impairment (Child-Pugh A). For moderate-severe (Child-Pugh B/C), use with caution; consider reducing sodium nitrite dose by 50% due to increased methemoglobinemia risk.
Pediatric use	Children: Sodium nitrite 0.15-0.33 mL/kg of 3% solution (4.5-10 mg/kg) IV push over 2 minutes, followed by sodium thiosulfate 1.65 mL/kg of 25% solution (412.5 mg/kg) IV push over 10 minutes. Repeat half doses if symptoms persist.
Geriatric use	Geriatric patients: Use weight-based dosing (same as adult). Start with lower doses (e.g., sodium nitrite 5 mg/kg) due to increased risk of hypotension and methemoglobinemia. Monitor vital signs frequently.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for NITHIODOTE (NITHIODOTE).

Breastfeeding	No human data; methylene blue is excreted in breast milk with an M/P ratio of approximately 0.7. Potential for infant methemoglobinemia; caution advised. Consider withholding breastfeeding for 4-6 hours after maternal dose.
Teratogenic Risk	FDA Pregnancy Category C. First trimester: Limited human data, animal studies show fetal malformations at high doses. Second and third trimesters: Potential risk of fetal methemoglobinemia and hemolytic anemia due to methylene blue component; avoid near term due to risk of neonatal methemoglobinemia.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to any component of the product","Children under 6 months of age (relative contraindication due to increased risk of hypotension and methemoglobinemia)"]

Clinical Precautions

Precautions

["May cause severe hypotension, especially in children","Risk of methemoglobinemia with excessive sodium nitrite","Use caution in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, as hemolysis may occur","Monitor methemoglobin levels, blood pressure, and oxygen saturation during therapy","Sodium thiosulfate may cause hypocalcemia in high doses"]

Clinical Tips & Counseling

Drug interactions

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NITHIODOTE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for NITHIODOTE (NITHIODOTE).

How it works

What the body does with it

Metabolism	Sodium nitrite is partially metabolized to nitric oxide and other metabolites; sodium thiosulfate is primarily excreted unchanged in urine, with minor metabolism by rhodanese in the liver and kidneys.
Excretion	Primarily renal as unchanged drug and metabolites; biliary/fecal excretion minimal (<5%).
Half-life	Terminal elimination half-life: 2.5–3 hours in adults with normal renal function; prolonged in renal impairment.
Protein binding	Approximately 90% bound to albumin.
Volume of Distribution	0.35 L/kg, indicating moderate tissue distribution.
Bioavailability	Oral: 60–80% (first-pass metabolism); IV: 100%.
Onset of Action	IV: immediate (within 2–5 minutes); oral: slower (15–30 minutes) due to absorption delay.
Duration of Action	IV: 4–6 hours (single dose); oral: 6–8 hours; repeat dosing may extend effect.

Classification & Brands

Dosing & administration

NITHIODOTE (sodium nitrite) 10 mg/kg IV push over 2 minutes, followed by sodium thiosulfate 50 mg/kg IV push over 10 minutes. Repeat half doses after 30 minutes if needed.

Dosage form	SOLUTION, SOLUTION
Renal impairment	No dose adjustment required for mild-moderate renal impairment (GFR >30 mL/min). For severe renal impairment (GFR <30 mL/min), consider reducing sodium thiosulfate dose by 50% and monitoring serum thiocyanate levels.
Liver impairment	No dose adjustment required for mild hepatic impairment (Child-Pugh A). For moderate-severe (Child-Pugh B/C), use with caution; consider reducing sodium nitrite dose by 50% due to increased methemoglobinemia risk.
Pediatric use	Children: Sodium nitrite 0.15-0.33 mL/kg of 3% solution (4.5-10 mg/kg) IV push over 2 minutes, followed by sodium thiosulfate 1.65 mL/kg of 25% solution (412.5 mg/kg) IV push over 10 minutes. Repeat half doses if symptoms persist.
Geriatric use	Geriatric patients: Use weight-based dosing (same as adult). Start with lower doses (e.g., sodium nitrite 5 mg/kg) due to increased risk of hypotension and methemoglobinemia. Monitor vital signs frequently.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for NITHIODOTE (NITHIODOTE).

Breastfeeding	No human data; methylene blue is excreted in breast milk with an M/P ratio of approximately 0.7. Potential for infant methemoglobinemia; caution advised. Consider withholding breastfeeding for 4-6 hours after maternal dose.
Teratogenic Risk	FDA Pregnancy Category C. First trimester: Limited human data, animal studies show fetal malformations at high doses. Second and third trimesters: Potential risk of fetal methemoglobinemia and hemolytic anemia due to methylene blue component; avoid near term due to risk of neonatal methemoglobinemia.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to any component of the product","Children under 6 months of age (relative contraindication due to increased risk of hypotension and methemoglobinemia)"]