Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 25% [250 mg/mL] (50 mL)
Pharmacology
Mechanism of Action
Cyanide toxicity: Serves as a sulfur donor in rhodanese-catalyzed formation of thiocyanate (much less toxic than cyanide)
Extravasation management: Neutralizes the reactive species of mechlorethamine; reduces the formation of hydroxyl radicals which cause tissue injury
Pharmacokinetics/Pharmacodynamics
Distribution
IV: Vd: Thiosulfate: 0.15 L/kg (Howland 2011); Thiocyanate: 0.25 L/kg
Excretion
Urine (~20% to 50% thiosulfate as unchanged drug)
Half-Life Elimination
Thiosulfate: ~3 hours (Howland 2011); Thiocyanate: 2.7 days, prolonged with renal impairment to ~9 days
Use: Labeled Indications
Cyanide poisoning: Treatment of acute, life-threatening cyanide poisoning in combination with sodium nitrite. Consider consultation with a poison control center at 1-800-222-1222.
Use: Off Label
Calciphylaxisc
Use of sodium thiosulfate in the treatment of calciphylaxis has been described primarily in case series and case reports and in a single retrospective review, it demonstrated beneficial effects in most patients, with partial to complete resolution of skin lesions and reductions in radiotracer activity on bone scans. Additional data may be necessary to further define the role of sodium thiosulfate in the treatment of this condition.
Management of mechlorethamine extravasationcyes
Clinical experience suggests the utility of sodium thiosulfate in managing mechlorethamine extravasation Albanell 2000, Dorr 1990, Ener 2004.
Based on the European Society for Medical Oncology (ESMO) and European Oncology Nursing Society (EONS) guidelines for management of chemotherapy extravasations, sodium thiosulfate given in the management of mechlorethamine extravasation is effective and recommended in the management of this condition Perez Fidalgo 2012.
Management of delayed calcium extravasation (calcinosis cutis)cyes
Clinical experience suggests the utility of sodium thiosulfate to treat delayed calcium extravasation in patients with severely debilitating, unresolving, or limb-threatening calcinosis cutis Reynolds 2014.
Management of concentrated cisplatin (≥0.4 mg/mL) extravasationc
Clinical experience suggests the utility of sodium thiosulfate in managing concentrated cisplatin (≥0.4 mg/mL) extravasation Albanell 2000, Dorr 1990, Ener 2004.
Management of bendamustine extravasationc
Clinical experience suggests the utility of sodium thiosulfate in managing bendamustine extravasation Schulmeister 2011.
Contraindications
There are no contraindications listed within the manufacturer's labeling.
Dosage and Administration
Dosing: Adult
Cyanide poisoning: IV: Note: Administer in conjunction with sodium nitrite. Administer sodium nitrite first, followed immediately by the administration of sodium thiosulfate: 12.5 g (50 mL of a 25% solution); may repeat at one-half the original dose if symptoms of cyanide toxicity return
Note: Monitor the patient for 24 to 48 hours; if symptoms return, repeat both sodium nitrite and sodium thiosulfate at one-half the original doses.
Calciphylaxis (off-label use): IV: Note: Optimal dose is not established.
Dialysis patients: 25 g administered 3 times per week during the last hour of or after the hemodialysis session. Therapy should continue until there is complete resolution of symptoms (Ackermann 2007; Auriemma 2011; Cicone 2004; Nigwekar 2013; Subramaniam 2008).
Patients not on dialysis (normal renal function or mildly reduced GFR): 25 g administered 3 times per week (Baker 2007; Hackett 2011).
Extravasation management (off-label use):
Mechlorethamine: SubQ (off-label route): Inject 2 mL of a 1/6 M (~4%) sodium thiosulfate solution (into the extravasation site) for each mg of mechlorethamine suspected to have extravasated (Pérez Fidalgo 2012; Polovich 2009)
Cisplatin, concentrated: Inject 2 mL of a 1/6 M (~4%) sodium thiosulfate solution into existing IV line for each 100 mg of cisplatin extravasated; consider also injecting 1 mL of a 1/6 M (~4%) sodium thiosulfate solution as 0.1 mL subcutaneous injections (clockwise) into the area around the extravasation, may repeat subcutaneous injections several times over the next 3-4 hours (Ener 2004)
Bendamustine: SubQ: Bendamustine extravasation may be managed with 1/6 M (~4%) sodium thiosulfate solution in the same manner as mechlorethamine extravasation (Schulmeister 2011)
Management of delayed calcium extravasation (calcinosis cutis) (off-label use): IV: 12.5 g over 30 minutes; may increase gradually to 25 g 3 times per week; monitor for non-anion gap acidosis, hypocalcemia, severe nausea (Reynolds 2014). Additional data may be necessary to further define the role of sodium thiosulfate for this condition.
Dosing: Geriatric
Refer to adult dosing; use with caution due to likelihood of decreased renal function.
Dosing: Pediatric
Cyanide poisoning: Note: Dosing in pediatric patients expressed in multiple units (mg/kg, mL/kg, mL/m2); use extra precaution. Administer in conjunction with sodium nitrite. Administer sodium nitrite first, followed immediately by the administration of sodium thiosulfate.
Infants, Children, and Adolescents: IV: 250 mg/kg (1 mL/kg or 30 to 40 mL/m2 of a 25% solution); maximum dose: 12.5 g/dose (50 mL of a 25% solution) (Howland 2019; manufacturer labeling). Monitor patients for 24 to 48 hours; if symptoms return, repeat both sodium nitrite and sodium thiosulfate at one-half the original doses.
Extravasation management: Limited data available:
Mechlorethamine extravasation: Children and Adolescents: SubQ: 1/6 M (~4%) solution: Inject 2 mL for each mg of mechlorethamine suspected to have extravasated, administer immediately into the extravasation site (Pérez Fidalgo 2012; Polovich 2009).
Cisplatin extravasation, concentrated: Infants, Children, and Adolescents: Inject 2 mL of a 1/6 M (~4%) sodium thiosulfate solution into existing IV line for each 100 mg of cisplatin extravasated; consider also injecting 1 mL of a 1/6 M (~4%) sodium thiosulfate solution as 0.1 mL subcutaneous injections (clockwise) into the area around the extravasation, may repeat subcutaneous injections several times over the next 3 to 4 hours (Ener 2004).
Reconstitution
Calciphylaxis (off-label use): May dilute dose in 100 mL of NS (Nigwekar 2013)
Extravasation management (off-label use/route): To prepare a 1/6 M solution for SubQ administration (off-label route), add 4 mL of a 10% sodium thiosulfate solution to 6 mL SWFI or 1.6 mL of a 25% sodium thiosulfate solution to 8.4 mL SWFI (Polovich 2009).
Administration
IV: Cyanide poisoning: Administer by IV infusion over 10 to 30 minutes immediately after the administration of sodium nitrite (Howland 2011). Decrease rate of infusion in the event of significant hypotension.
Calciphylaxis (off-label use): Administer by IV infusion over 30 to 60 minutes (Cicone 2004; Nigwekar 2013).
Extravasation management (off-label use): Stop vesicant infusion immediately and disconnect IV line (leave needle/cannula in place); gently aspirate extravasated solution from the IV line (do NOT flush the line); remove needle/cannula (temporarily keep in place for cisplatin extravasation to allow for sodium thiosulfate administration through the needle/cannula); elevate extremity.
Mechlorethamine: Inject subcutaneously (off-label route) into the extravasation site using ≤25-gauge needle; change needle with each injection (Pérez Fidalgo 2012; Polovich 2009).
Cisplatin, concentrated: Inject into the existing IV line; consider also injecting 1 mL as 0.1 mL subcutaneous injections (clockwise) into the area around the extravasation using a new 25- or 27-gauge needle for each injection (Ener 2004).
Bendamustine: SubQ: Bendamustine extravasation may be managed with sodium thiosulfate in the same manner as mechlorethamine extravasation (Schulmeister 2011).
Storage
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light. Do not freeze.
Extravasation management (off-label use/route): Store the 1/6 M solution for SubQ administration at 15°C to 30°C (59°F to 86°F) (Polovich 2009).
Drug Interactions
There are no known significant interactions.
Adverse Reactions
Frequency not defined
Cardiovascular: Hypotension
Central nervous system: Disorientation, flushing sensation, headache, salty taste
Gastrointestinal: Nausea, vomiting
Hematologic & oncologic: Prolonged bleeding time
Warnings/Precautions
Special populations:
- Fire victims: Fire victims may present with both cyanide and carbon monoxide poisoning. In these patients, the induction of methemoglobinemia with amyl nitrite or sodium nitrite is contraindicated until carbon monoxide levels return to normal due to the risk of tissue hypoxia. Methemoglobinemia decreases the oxygen-carrying capacity of hemoglobin and the presence of carbon monoxide prevents hemoglobin from releasing oxygen to the tissues. In this scenario, sodium thiosulfate may be used alone to promote the clearance of cyanide. However, hydroxocobalamin is the preferred cyanide antidote and should be considered to avoid the nitrite-related problems and because sodium thiosulfate has a slow onset of action.
- Sulfite hypersensitivity: The presence of sulfite hypersensitivity should not preclude the use of this medication.
Other warnings/precautions:
- Appropriate use: Cyanide poisoning: Due to the risk for serious adverse effects, use with caution in patients where the diagnosis of cyanide poisoning is uncertain. However, if clinical suspicion of cyanide poisoning is high, treatment should not be delayed. Signs of cyanide poisoning may include altered mental status, mydriasis, nausea/vomiting, dyspnea, chest tightness, hyper-/hypotension, plasma lactate ≥8 mmol/L. Treatment of cyanide poisoning should include external decontamination and supportive therapy. Consider consultation with a poison control center at 1-800-222-1222.
- Initiation of treatment: Collection of pretreatment blood cyanide concentrations does not preclude administration and should not delay administration in the emergency management of highly suspected or confirmed cyanide toxicity. Pretreatment levels may be useful as postinfusion levels may be inaccurate.
- Return of symptoms: Patients receiving treatment for acute cyanide toxicity must be monitored for return of symptoms for 24 to 48 hours; repeat treatment (one-half the original dose) should be administered if symptoms return.
Monitoring Parameters
Cyanide poisoning: Monitor for at least 24-48 hours after administration; blood pressure and heart rate during and after infusion; hemoglobin/hematocrit; co-oximetry; serum lactate levels; venous-arterial PO2 gradient; serum methemoglobin and oxyhemoglobin. Pretreatment cyanide levels may be useful diagnostically.
Extravasation management: Monitor and document extravasation site for pain, blister formation, skin sloughing, arm/hand swelling/stiffness; monitor for fever, chills, or worsening pain
When used in the management of delayed calcium extravasation (calcinosis cutis), monitor for non-anion gap acidosis, hypocalcemia, severe nausea (Reynolds 2014).
Pregnancy
Pregnancy Risk Factor
C
Pregnancy Considerations
Teratogenic effects were not observed in animal reproduction studies of sodium thiosulfate. In general, medications used as antidotes should take into consideration the health and prognosis of the mother; antidotes should be administered to pregnant women if there is a clear indication for use and should not be withheld because of fears of teratogenicity (Bailey 2003).
Patient Education
What is this drug used for?
- It is used to treat cyanide poisoning.
- It may be given to you for other reasons. Talk with the doctor.
Frequently reported side effects of this drug
- Nausea
- Vomiting
- Headache
- Sensation of warmth
- Bad taste
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Severe dizziness
- Passing out
- Confusion
- Bruising
- Bleeding
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
