Sodium Thiosulfate (Antidote) (Monograph)

Drug class: Antidotes
Chemical name: dioxido-oxo-sulfanylidene-lambda6-sulfane
Molecular formula: 2NA•O₃S₂•5H₂O
CAS number: 14383-50-7, 10102-17-7

Medically reviewed by Drugs.com on Feb 27, 2023. Written by ASHP.

Introduction

Sodium thiosulfate is a cyanide antidote.

Uses for Sodium Thiosulfate (Antidote)

Acute Cyanide Poisoning

Sodium thiosulfate 250 mg/mL injection is indicated for sequential use with sodium nitrite for treatment of acute cyanide poisoning that is judged to be serious or life-threatening.

If clinical suspicion of cyanide poisoning is high, administer sodium thiosulfate and sodium nitrite without delay and in conjunction with appropriate airway, ventilatory, and circulatory support. Sodium nitrite causes hypotension and methemoglobin formation, which diminishes oxygen carrying capacity. Because of these risks, sodium thiosulfate and sodium nitrite should be used with caution in patients where the diagnosis of cyanide poisoning is uncertain.

Comprehensive treatment of acute cyanide intoxication requires support of vital functions. Administration of sodium nitrite and sodium thiosulfate should be considered adjunctive to appropriate supportive therapies. Airway, ventilatory and circulatory support, and oxygen administration should not be delayed in order to administer sodium nitrite and sodium thiosulfate. The expert advice of a regional poison control center may be obtained by calling 1-800-222-1222.

The human data supporting the use of sodium thiosulfate and sodium nitrite for cyanide poisoning consists primarily of published case reports. There are no randomized controlled clinical trials. Nearly all the human data describing the use of sodium thiosulfate report its use in conjunction with sodium nitrite. Dosing recommendations for humans have been based on theoretical calculations of antidote detoxifying potential, extrapolation from animal experiments, and a small number of human case reports.

Related/similar drugs

amyl nitrite, hydroxocobalamin, sodium thiosulfate, Cyanokit

Sodium Thiosulfate (Antidote) Dosage and Administration

General

Sodium thiosulfate is available in the following dosage form(s) and strength(s):

Injection: 12.5 g/50 mL (250 mg/mL) in a single-dose vial indicated for treatment of cyanide poisoning; also available in a kit with sodium nitrite injection 300 mg/10 mL (30 mg/mL) in single-dose vials for the treatment of cyanide poisoning.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Pediatric Patients

Acute Cyanide Poisoning

Sodium nitrite and sodium thiosulfate should be administered as early as possible after a diagnosis of acute life-threatening cyanide poisoning has been established. Both drugs are administered by slow IV injection. Sodium nitrite should be administered first, followed immediately by sodium thiosulfate. (See Table 1 for dosage recommendations.) Blood pressure must be monitored during infusion. The rate of infusion should be decreased if significant hypotension is noted.

If signs of poisoning reappear, repeat treatment using one-half the original dose of both sodium nitrite and sodium thiosulfate.

In patients with known anemia, it is recommended that the dosage of sodium nitrite should be reduced proportionately to the hemoglobin concentration.

Patients should be monitored for at least 24–48 hours after sodium thiosulfate administration for adequacy of oxygenation and perfusion and for recurrent signs and symptoms of cyanide toxicity. When possible, obtain hemoglobin/hematocrit 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.

The safety of administering other cyanide antidotes simultaneously with sodium thiosulfate has not been established. If a decision is made to administer another cyanide antidote with sodium thiosulfate, these drugs should not be administered concurrently in the same IV line.

Adults

Acute Cyanide Poisoning

Sodium nitrite and sodium thiosulfate should be administered as early as possible after a diagnosis of acute life-threatening cyanide poisoning has been established. Both drugs are administered by slow IV injection. Sodium nitrite should be administered first, followed immediately by sodium thiosulfate. (See Table 3 for dosage recommendations.) Blood pressure must be monitored during infusion. The rate of infusion should be decreased if significant hypotension is noted.

If signs of poisoning reappear, repeat treatment using one-half the original dose of both sodium nitrite and sodium thiosulfate.

In patients with known anemia, it is recommended that the dosage of sodium nitrite should be reduced proportionately to the hemoglobin concentration.

Patients should be monitored for at least 24–48 hours after sodium thiosulfate administration for adequacy of oxygenation and perfusion and for recurrent signs and symptoms of cyanide toxicity. When possible, obtain hemoglobin/hematocrit 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.

The safety of administering other cyanide antidotes simultaneously with sodium thiosulfate has not been established. If a decision is made to administer another cyanide antidote with sodium thiosulfate, these drugs should not be administered concurrently in the same IV line.

Cautions for Sodium Thiosulfate (Antidote)

Contraindications

• None.

Warnings/Precautions

Life-threatening Hypotension and Methemoglobin Formation with Sodium Nitrite

When sodium thiosulfate is used in combination with sodium nitrite in patients with acute cyanide poisoning, the warnings and precautions of sodium nitrite should be considered. A boxed warning has been included about the risk of life-threatening hypotension and methemoglobin formation in the prescribing information for sodium nitrite. Sodium nitrite can cause serious adverse reactions and death in humans, even at doses less than twice the recommended therapeutic dose. Sodium nitrite causes hypotension and methemoglobin formation, which diminishes oxygen carrying capacity. Hypotension and methemoglobin formation can occur concurrently or separately.

Because of these risks, sodium nitrite should be used to treat acute life-threatening cyanide poisoning and be used with caution in patients where the diagnosis of cyanide poisoning is uncertain. Patients should be closely monitored to ensure adequate perfusion and oxygenation during treatment with sodium nitrite. Alternative therapeutic approaches should be considered in patients known to have diminished oxygen or cardiovascular reserve (e.g., smoke inhalation victims, pre-existing anemia, cardiac or respiratory compromise) and those at higher risk of developing methemoglobinemia (e.g., congenital methemoglobin reductase deficiency) as they are at greater risk for potentially life-threatening adverse events related to the use of sodium nitrite.

Hypersensitivity

Sodium thiosulfate preparations may contain sodium sulfite. The manufacturer of the sodium thiosulfate preparation indicated for acute cyanide poisoning states that the presence of a trace amount of sulfites in the product should not deter administration of the drug for treatment of emergency situations, even if the patient is sulfite-sensitive.

Specific Populations

Pregnancy

There are no available data on sodium thiosulfate use in pregnant women to evaluate for a drug-associated risk.

There are risks to the pregnant woman and fetus associated with untreated cyanide poisoning. Therefore, if a pregnant woman has known or suspected cyanide poisoning, sodium thiosulfate injection for sequential use with sodium nitrite is recommended.

In published animal studies, no evidence of embryotoxicity or malformations was reported when sodium thiosulfate was administered during organogenesis to pregnant mice, rats, hamsters, or rats at 0.2 to 0.9 times the human daily dose of 12.5 g for cyanide poisoning. The studies did not test doses that were comparable to the human dose for cyanide poisoning.

Lactation

Because of the potential for serious adverse reactions in the breastfed infant, the manufacturer of the sodium thiosulfate preparation indicated for acute cyanide poisoning states that breastfeeding is not recommended during treatment with the drug. There are no data to determine when breastfeeding may be safely restarted following the administration of sodium thiosulfate.

Pediatric Use

There are case reports in the medical literature of sodium nitrite in conjunction with sodium thiosulfate being administered to pediatric patients with cyanide poisoning; however, there have been no clinical studies to evaluate the safety or efficacy of sodium thiosulfate in the pediatric population.

Common Adverse Effects

Most common adverse reactions are hypotension, headache, and disorientation.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Formal drug interaction studies have not been conducted with sodium thiosulfate injection.

Actions

Mechanism of Action

Exposure to a high dose of cyanide can result in death within minutes due to the inhibition of cytochrome oxidase resulting in arrest of cellular respiration. Specifically, cyanide binds rapidly with cytochrome a3, a component of the cytochrome c oxidase complex in mitochondria. Inhibition of cytochrome a3 prevents the cell from using oxygen and forces anaerobic metabolism, resulting in lactate production, cellular hypoxia and metabolic acidosis. In massive acute cyanide poisoning, the mechanism of toxicity may involve other enzyme systems as well. The synergy resulting from treatment of cyanide poisoning with the combination of sodium nitrite and sodium thiosulfate is the result of differences in their primary mechanisms of action as antidotes for cyanide poisoning.

Sodium nitrite: Sodium nitrite is thought to exert its therapeutic effect by reacting 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. Methemoglobin displaces cyanide from cytochrome oxidase, allowing resumption of aerobic metabolism. Vasodilation has also been cited to account for at least part of the therapeutic effect of sodium nitrite. It has been suggested that sodium nitrite-induced methemoglobinemia may be more efficacious against cyanide poisoning than comparable levels of methemoglobinemia induced by other oxidants. Also, sodium nitrite appears to retain some efficacy even when the formation of methemoglobin is inhibited by methylene blue.

Sodium thiosulfate: The primary route of endogenous cyanide detoxification is by enzymatic transulfuration to thiocyanate (SCN), which is relatively nontoxic and readily excreted in the urine. Sodium thiosulfate is thought to serve as a sulfur donor in the reaction catalyzed by the enzyme rhodanese, thus enhancing the endogenous detoxification of cyanide.

Advice to Patients

• When feasible, patients receiving sodium thiosulfate for cyanide poisoning should be informed of the possibility of hypotension.

• Where feasible, patients receiving sodium thiosulfate for cyanide poisoning should be informed of the need for close monitoring of blood pressure and oxygenation.

• Advise women that breastfeeding is not recommended during treatment with sodium thiosulfate injection.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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