NITHIODOTE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NITHIODOTE (NITHIODOTE).
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.
| 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. |
| Molecular Weight | 324.35 |
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. |
| 1st trimester | Use is contraindicated in pregnancy; has been associated with adverse fetal outcomes in animal studies. |
| 2nd trimester | Contraindicated; may cause fetal harm. |
| 3rd trimester | Contraindicated; potential for neonatal toxicity. |
Clinical note
Comprehensive clinical and safety monograph for NITHIODOTE (NITHIODOTE).
| Placental transfer | Crosses placenta; evidence of transfer in animal studies. |
| Breastfeeding | Excreted in breast milk; potential for serious adverse reactions in the breastfed infant. Use is not recommended. |
| Lactation Rating | L5 - Contraindicated |
■ FDA Black Box Warning
None
| Serious Effects |
PregnancyHypersensitivity to nithiodote or any componentBreastfeeding
| 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 |
| Food/Dietary | No known food interactions. Avoid alcohol as it may impair liver function and worsen acidosis. |
| Clinical Pearls |
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| 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. |
| Fetal Monitoring | Monitor maternal methemoglobin levels, oxygen saturation, and hemoglobin. Assess fetal heart rate during infusion. Evaluate for neonatal methemoglobinemia at delivery. |
| Fertility Effects | In animal studies, high doses of methylene blue impaired fertility and caused testicular atrophy. No human data. |
| NITHIODOTE (sodium nitrite and sodium thiosulfate) is indicated for acute cyanide poisoning. Administer intravenously as soon as possible after exposure. Monitor methemoglobin levels; do not exceed 20% methemoglobinemia. Use with caution in patients with G6PD deficiency due to risk of hemolytic anemia. Sodium nitrite induces methemoglobinemia which can impair oxygen delivery; ensure adequate ventilation. Sodium thiosulfate is generally safer and can be given separately. |
| Patient Advice | This medication is only used in hospital settings for cyanide poisoning. · It is given through an IV line as soon as possible after exposure. · You may experience symptoms of low oxygen such as headache, confusion, or blue skin due to methemoglobin formation. · Tell your doctor if you have a history of G6PD deficiency, anemia, or breathing problems. · Follow-up blood tests will be needed to monitor your oxygen levels and blood counts. |