Sodium thiosulfate & sodium nitrite

Name: Sodium thiosulfate & sodium nitrite

Dosing & Uses

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

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%)

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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