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Sodium Thiosulfate

Pronunciation

(SOW dee um thye oh SUL fate)

Index Terms

  • Disodium Thiosulfate Pentahydrate
  • Pentahydrate
  • Sodium Hyposulfate
  • Sodium Thiosulphate
  • Thiosulfuric Acid Disodium Salt

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

Generic: 10% [100 mg/mL] (10 mL [DSC]); 25% [250 mg/mL] (50 mL)

Pharmacologic Category

  • Antidote
  • Antidote, Extravasation

Pharmacology

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

Excretion

Urine (~20% to 50% as unchanged drug)

Half-Life Elimination

Thiosulfate: ~3 hours (Howland 2011); Thiocyanate: ~3 days; Renal impairment: ≤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.

Off Label Uses

Calciphylaxis

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 extravasation

Clinical experience suggests the utility of sodium thiosulfate in managing mechlorethamine extravasation [Albanell 2000], [Dorr 1990], [Ener 2004]. Additional data may be necessary to further define the role of sodium thiosulfate for this condition.

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)

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]. Additional data may be necessary to further define the role of sodium thiosulfate for this condition.

Management of concentrated cisplatin (≥0.4 mg/mL) extravasation

Clinical experience suggests the utility of sodium thiosulfate in managing concentrated cisplatin (≥0.4 mg/mL) extravasation [Albanell 2000], [Dorr 1990], [Ener 2004]. Additional data may be necessary to further define the role of sodium thiosulfate for this condition.

Management of bendamustine extravasation

Clinical experience suggests the utility of sodium thiosulfate in managing bendamustine extravasation [Schulmeister 2011]. Additional data may be necessary to further define the role of sodium thiosulfate for this condition.

Contraindications

There are no contraindications listed within the manufacturer’s labeling.

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: IV: Note: Administer in conjunction with sodium nitrite. Administer sodium nitrite first, followed immediately by the administration of sodium thiosulfate. 250 mg/kg (1 mL/kg or ~30 to 40 mL/m2 of a 25% solution) or 500 mg/kg (2 mL/kg of a 25% solution) (Howland 2011); maximum dose: 12.5 g (50 mL of a 25% solution) (Mintegi 2013); may repeat at one-half the original dose if symptoms of cyanide toxicity return

Note: Monitor the patient for 24-48 hours; if symptoms return, repeat both sodium nitrite and sodium thiosulfate at one-half the original doses.

Dosing: Renal Impairment

No dosage adjustment provided in manufacturer’s labeling; however, renal elimination is significant and risk of adverse effects may be increased in patients with renal impairment.

Calciphylaxis (off-label use): No dosage adjustment necessary. When used for patients not on dialysis (normal renal function or mildly reduced GFR), because sodium thiosulfate is cleared by the kidney, dose may be adjusted based on appearance of adverse effects (eg, metabolic acidosis, hypotension) (Hackett 2011; Nigwekar 2013).

Dosing: Hepatic Impairment

No dosage adjustment provided in the manufacturer’s labeling (has not been studied).

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 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 24-48 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 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

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, vomiting, headache, sensation of warmth, or bad taste. Have patient report immediately to prescriber severe dizziness, passing out, confusion, bruising, or bleeding (HCAHPS).

• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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