Dosing and uses of Nithiodote (sodium thiosulfate and sodium nitrite)
Adult dosage forms and strengths
per carton
- sodium thiosulfate injection: 250mg/mL (12.5g/50mL vial) 1 vial
- sodium nitrite injection: 30mg/mL (300mg/10mL vial) 1 vial
Cyanide Poisoning
Sodium nitrite: 300 mg (ie, 10 mL) IV infused at rate of 2.5-5 mL/minute
Sodium thiosulfate: 12.5 g (ie, 50 mL) slow IV infusion (over 10 minutes) immediately following sodium nitrite; adjust infusion rate according to blood pressure
If signs of poisoning reappear, repeat treatment using one-half the original dose of both sodium nitrite and sodium thiosulfate
Anemia: Reduce dose of sodium nitrite proportional to hemoglobin concentration
Renal Impairment
Substantially excreted by the kidney; risk of toxic reactions to these drugs may be greater in patients with impaired renal function
Pediatric dosage forms and strengths
per carton
- sodium thiosulfate injection: 250mg/mL (12.5g/50mL vial) 1 vial
- sodium nitrite injection: 30mg/mL (300mg/10mL vial) 1 vial
Cyanide Poisoning
Sodium nitrite: 6 mg/kg (ie, 0.2 mL/kg of 3% solution) IV infused at rate of 2.5-5 mL/minute; not to exceed 10 mL (300 mg)
Sodium thiosulfate: 250 mg/kg (ie, 1 mL/kg of 25% solution) slow IV infusion (over 10 minutes) immediately following sodium nitrite; adjust infusion rate according to blood pressure
If signs of poisoning reappear, repeat treatment using one-half the original dose of both sodium nitrite and sodium thiosulfate
Anemia: Reduce dose of sodium nitrite proportional to hemoglobin concentration
Renal Impairment
Substantially excreted by the kidney; risk of toxic reactions to these drugs may be greater in patients with impaired renal function
Geriatric dosage forms and strengths
Known to be substantially excreted by the kidney; risk of toxic reactions to these drugs may be greater in patients with impaired renal function
Nithiodote (sodium thiosulfate and sodium nitrite) adverse (side) effects
Frequency not defined (sodium nitrite)
Syncope
Hypotension
Tachycardia
Palpitations
Dysrhythmia
Methemoglobinemia
Headache
Dizziness
Blurred vision
Seizures
Confusion
Coma
Frequency not defined (sodium thiosulfate)
Hypotension
Headache
Disorientation
Warnings
Black box warnings
Sodium nitrite can cause serious adverse reactions and death from hypotension and methemoglobin formation
Monitor to ensure adequate perfusion and oxygenation during treatment with sodium nitrite
Cautions
Methemoglobinemia: Sodium nitrite reacts with hemoglobin to form methemoglobin and should be used with caution in patients known to have anemia
Smoke inhalation: Carbon monoxide contained in smoke can result in the formation of carboxyhemoglobin that can reduce the oxygen carrying capacity of the blood; sodium nitrite should be used with caution in patients with smoke inhalation injury because of the potential for worsening hypoxia due to methemoglobin formation
Optimally, the sodium nitrite dose should be reduced in proportion to the oxygen carrying capacity
Use with caution if the diagnosis of cyanide poisoning is uncertain
Monitoring
- Monitor patients for at least 24-48 hr after administration for adequacy of oxygenation and perfusion and for recurrent signs and symptoms of cyanide toxicity
- When possible, hemoglobin/hematocrit should be obtained when treatment is initiated
- Measurements of oxygen saturation using standard pulse oximetry and calculated oxygen saturation values based on measured PO2 are unreliable in the presence of methemoglobinemia
- Methemoglobin level: Administrations of sodium nitrite solely to achieve an arbitrary level of methemoglobinemia may be unnecessary and potentially hazardous; therapeutic effects of sodium nitrite do not appear to be mediated by methemoglobin formation alone and clinical responses to sodium nitrite administration have been reported in association with methemoglobin levels <10%
- Administration of sodium nitrite beyond the initial dose should be guided primarily by clinical response to treatment (ie, a second dose should be considered only if there is inadequate clinical response to the first dose)
- Methemoglobin concentrations be closely monitored and kept below 30%; serum methemoglobin levels should be monitored during treatment using co-oximetry, and administration of sodium nitrite should generally be discontinued when methemoglobin levels exceed 30%
- Intravenous methylene blue and exchange transfusion have been reported in the literature as treatments for life-threatening methemoglobinemia
Pregnancy and lactation
Pregnancy category: C; sodium nitrite has caused fetal death in humans as well as animals
Lactation: unknown whether distributed in breast milk, caution advised
Because these drugs may be administered in life-threatening situations, breast-feeding is not a contraindication to its use; there are no data to determine when breastfeeding may be safely restarted following administration of sodium nitrite and sodium thiosulfate
In studies conducted with Long-Evans rats, sodium nitrite administered in drinking water during pregnancy and lactation resulted in severe anemia, reduced growth and increased mortality in the offspring
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Nithiodote (sodium thiosulfate and sodium nitrite)
Half-Life (thiocyanate): 2.7 days; 9 days with renal insufficiency
Metabolism
Sodium nitrite: 60% is metabolized to ammonia and related small molecules
Sodium thiosulfate: Enzymatic transulfuration to thiocyanate
Excretion
Sodium nitrite: 40% excreted unchanged in urine
Thiocyanate: excreted mainly in urine
Mechanism of action
Nitrites create methemoglobins to bind to cyanide
sodium thiosulfate
- Primary route of endogenous cyanide detoxification is by enzymatic transulfuration to thiocyanate (SCN-), which is relatively nontoxic and readily excreted in the urine
- Thought to serve as a sulfur donor in the reaction catalyzed by the enzyme rhodanese, thus enhancing the endogenous detoxification of cyanide
sodium nitrite
- Reacts with hemoglobin to form methemoglobin, an oxidized form of hemoglobin incapable of oxygen transport but with high affinity for cyanide; cyanide preferentially binds to methemoglobin over cytochrome a3, forming the nontoxic cyanomethemoglobin
- Vasodilation has also been cited to account for at least part of the therapeutic effect of sodium nitrite
Administration
IV Incompatibilities
Y-site: hydroxocobalamin
Storage
Store at controlled room temperature between 20°C and 25°C (68°F - 77°F); excursions permitted to 15-30°C (59 to 86°F)
Protect from direct light
Do not freeze
