sodium thiosulfate & sodium nitrite (Rx)

Brand and Other Names:Nithiodote
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Dosing & Uses

AdultPediatricGeriatric

Dosing Form & Strengths

kit

  • 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 (50 mL of 25% solution) slow IV infusion (over 10 minutes) immediately following sodium nitrite administration; 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

Hepatic Impairment

Not studied

Dosing Form & Strengths

kit

  • 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 or 8 mL/m² BSA 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 or 30-40 mL/m² BSA 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

Known to be substantially excreted by the kidney; risk of toxic reactions to these drugs may be greater in patients with impaired renal function

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Adverse Effects

Frequency Not Defined

Sodium nitrite

  • Syncope
  • Hypotension
  • Tachycardia
  • Palpitations
  • Diaphoresis
  • Dyspnea
  • Dysrhythmia
  • Methemoglobinemia
  • Headache
  • Dizziness
  • Tachypnea
  • Blurred vision
  • Seizures
  • Confusion
  • Coma

Sodium thiosulfate

  • Hypotension
  • Headache
  • Disorientation
  • Nausea/vomiting
  • Salty taste
  • Prolonged bleeding time
  • Warmth
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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

Coadministration with antihypertensive, phosphodiesterase-5 enzyme or diuretics should be done with caution

Use caution in patients with anemia

Patients with G6PD deficiency are at increased risk of hemolytic crisis

Avoid nitites in pregnancy due to fetal hemoglobin's susceptibility to oxidase stress

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
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Pregnancy & 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.

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Pharmacology

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 thereby allowing aerobic metabolism to continue
  • Vasodilation has also been cited to account for at least part of the therapeutic effect of sodium nitrite

Pharmacokinetics

Half-Life

  • Thiosulfate: 2 hr; 3 days (thiocyanate); 9 days (renal impairment)

Onset

  • Methemoglobinemia: 30-60 min

Duration

  • Sodium thiosulfate: 55 min (methemoglobinemia)

Metabolism

  • Sodium nitrite: 60% is metabolized to ammonia and related small molecules
  • Sodium thiosulfate: Enzymatic transulfuration to thiocyanate

Excretion

  • Sodium nitrite: Urine (40% excreted unchanged)
  • Sodium thiosulfate: Urine (20-50%)
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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

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Formulary

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Tier Description
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.