Cyanide poisoning (alternative agent): Note: If hydroxocobalamin is unavailable, then sodium nitrite may be used in conjunction with sodium thiosulfate; administer sodium nitrite first, followed immediately by the administration of sodium thiosulfate (Ref). The benefit of sodium thiosulfate in combination with hydroxocobalamin has been questioned; however, cases of favorable outcomes following severe poisonings have been reported (Ref). Consider consultation with a clinical toxicologist or poison control center.
IV: 12.5 g (50 mL of a 25% solution); may repeat at one-half the original dose if symptoms of cyanide toxicity return.
Calciphylaxis (off-label use): Note: Optimal dose is not established.
Patients on dialysis: IV: 25 g administered 3 times per week during the last hour of or after the hemodialysis session. Continue therapy until there is complete resolution of symptoms (Ref).
Patients not on dialysis (normal renal function or mildly reduced GFR): IV: 25 g administered 3 times per week (Ref).
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 (Ref).
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 SUBQ injections (clockwise) into the area around the extravasation, may repeat SUBQ injections several times over the next 3 to 4 hours (Ref).
Bendamustine: SUBQ: Bendamustine extravasation may be managed with 1/6 M (~4%) sodium thiosulfate solution in the same manner as mechlorethamine extravasation (Ref).
Management of delayed calcium extravasation (calcinosis cutis) (off-label use): Note: Closely monitor site; most calcifications spontaneously resolve. However, if a severe manifestation of calcinosis cutis occurs, may initiate sodium thiosulfate antidote (Ref).
IV: 12.5 g over 30 minutes, administered 3 times per week; may increase gradually to 25 g 3 times per week; monitor for non-anion gap acidosis, hypocalcemia, severe nausea (Ref).
There are no dosage adjustments provided in the 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) (Ref).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing.
(For additional information see "Sodium thiosulfate: Pediatric drug information")
Note: Parenteral sodium thiosulfate is available as two separate products with unique indications, concentrations, and dosing which should not be interchanged.
Cisplatin-induced ototoxicity; risk reduction:
Note: Reserve use for patients receiving cisplatin infusions ≤6 hours duration; with cisplatin infusions >6 hours, irreversible ototoxicity may have already occurred and sodium thiosulfate may not reduce this risk. Prior to each sodium thiosulfate dose, administer antiemetic therapy and ensure that sodium level is within normal limits.
Infants, Children, and Adolescents:
Pedmark (125 mg/mL solution):
<5 kg: IV: 10 g/m2/dose 6 hours after completion of each cisplatin infusion. Note: If cisplatin is a multiday regimen, administer at least 10 hours prior to next cisplatin dose if able; however, if subsequent dose due in <10 hours, do not administer sodium thiosulfate. Refer to individual protocols (Ref).
5 to 10 kg: IV: 15 g/m2/dose 6 hours after completion of each cisplatin infusion. Note: If cisplatin is a multiday regimen, administer at least 10 hours prior to next cisplatin dose if able; however, if subsequent dose due in <10 hours, do not administer sodium thiosulfate. Refer to individual protocols (Ref).
>10 kg: IV: 20 g/m2/dose 6 hours after completion of each cisplatin infusion. Note: If cisplatin is a multiday regimen, administer at least 10 hours prior to next cisplatin dose if able; however, if subsequent dose due in <10 hours, do not administer sodium thiosulfate. Refer to individual protocols (Ref).
Cyanide poisoning:
Note: Hydroxocobalamin is the preferred cyanide antidote; if hydroxocobalamin is unavailable, sodium nitrite may be used in conjunction with sodium thiosulfate. Administer sodium nitrite first, followed immediately by the administration of sodium thiosulfate (Ref). Dosing in pediatric patients is based on the 250 mg/mL (25%) solution and expressed in multiple units (mg/kg, mL/kg); use extra caution. Administer in conjunction with sodium nitrite. Consider consultation with a clinical toxicologist or poison control center.
Infants, Children, and Adolescents: 250 mg/mL solution (25%): IV: 250 to 412.5 mg/kg (1 to 1.65 mL/kg of a 25% solution); maximum dose: 12.5 g/dose (50 mL of a 25% solution) (Ref). 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 (Ref).
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 SUBQ injections (clockwise) into the area around the extravasation; may repeat SUBQ injections several times over the next 3 to 4 hours (Ref).
Dosing adjustment for toxicity:
Cisplatin-induced ototoxicity; risk reduction:
Infants, Children, and Adolescents: Sodium thiosulfate (125 mg/mL): Pedmark: IV:
Adverse Reaction |
Severity |
Dosage Modification |
---|---|---|
Hypernatremia |
>145 mmol/L |
Withhold sodium thiosulfate (Pedmark) and administer supportive care as needed. When sodium is within normal limits, resume therapy at same dose. |
Hypokalemia |
Grade 3 or 4 |
Withhold sodium thiosulfate (Pedmark) and supplement potassium as needed. When potassium is within normal limits, resume therapy at same dose. |
Hypersensitivity reaction |
Grade 1 or 2 |
Immediately stop sodium thiosulfate (Pedmark) infusion and administer appropriate care. Administer antihistamines or glucocorticoids (if appropriate) prior to subsequent doses. |
Grade 3 or 4 |
Immediately stop sodium thiosulfate (Pedmark) and administer appropriate care. Permanently discontinue sodium thiosulfate (Pedmark). | |
Other adverse reactions |
Grade 3 |
Withhold sodium thiosulfate (Pedmark) until ≤ grade 1. Resume at the same dose. |
Grade 4 |
Permanently discontinue sodium thiosulfate (Pedmark). |
There are no dosage adjustments provided in the manufacturer's labeling; however, renal elimination of sodium thiosulfate is significant and risk of adverse effects may be increased in patients with renal impairment.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
The following adverse drug reactions are derived from product labeling unless otherwise specified. Reported adverse reactions are for infants, children, and adolescents administered sodium thiosulfate concomitantly with cisplatin, unless otherwise specified.
Frequency not defined:
Endocrine & metabolic: Hypermagnesemia, hypernatremia, hypokalemia, hyponatremia, hypophosphatemia
Gastrointestinal: Nausea, stomatitis, vomiting
Hematologic & oncologic: Decreased hemoglobin
Miscellaneous: Fever
Postmarketing (any population; sodium thiosulfate may be administered with either cisplatin or sodium nitrite):
Cardiovascular: Hypertension, hypotension
Endocrine & metabolic: Hypercalcemia (Shen 2019), hypocalcemia, metabolic acidosis (Sohal 2020)
Gastrointestinal: Salty taste
Hematologic & oncologic: Prolonged bleeding time, prolonged prothrombin time
Local: Localized warm feeling
Nervous system: Disorientation, headache
Pedmark: History of severe hypersensitivity to sodium thiosulfate or any component of the formulation.
Concerns related to adverse effects:
• Electrolyte abnormalities: Pedmark: Hypernatremia and hypokalemia may occur. Do not initiate treatment with baseline serum sodium >145 mmol/L; initiate appropriate treatment as necessary.
• GI effects: Pedmark: Nausea and vomiting may occur. Premedication with antiemetics may be administered; initiate additional antiemetics and supportive care as needed.
• Hypersensitivity: Pedmark: Hypersensitivity reactions has been reported. Immediately discontinue treatment and initiate appropriate care as needed if hypersensitivity occurs.
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: May contain sodium sulfite; sulfite exposure may cause hypersensitivity reactions, including anaphylaxis and life-threatening or severe asthma episodes in susceptible patients. The presence of sulfite hypersensitivity should not preclude the use of this medication when being used for cyanide poisoning.
Dosage form considerations:
• Parenteral sodium thiosulfate is available as two separate products with unique indications, concentrations, and dosing which should not be interchanged.
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 clinical toxicologist or poison control center. Ototoxicity risk reduction: Safety and efficacy have not been established when administered following cisplatin infusions >6 hours; with cisplatin infusions >6 hours, irreversible ototoxicity may have already occurred and sodium thiosulfate may not reduce this risk.
• Initiation of treatment: Cyanide poisoning: 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: Cyanide poisoning: 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.
Electrolyte abnormalities (hypernatremia, hypokalemia) have been reported in pediatric ototoxicity risk reduction clinical trials. Hypernatremia developed in 12% to 26% of patients, including grade 3 in one patient. A sodium thiosulfate dose of 20 g/m2 contains 162 mmol/m2 of sodium, a 15 g/m2 dose contains 121 mmol/m2 of sodium, and 10 g/m2 contains 81 mmol/m2 of sodium. Do not administer sodium thiosulfate (Pedmark) in patients with serum sodium levels >145 mmol/L. Due to an underdeveloped sodium homeostasis system compared to older infants, use of sodium thiosulfate (Pedmark) is not recommended in neonatal patients. Hypokalemia was reported in 15% to 27% of patients. Patients should be monitored for signs of hypernatremia and hypokalemia and treated and supplemented as needed.
When used to reduce the risk of ototoxicity from cisplatin, there is an increased risk of nausea and vomiting in pediatric patients; antiemetics should be given prior to administration.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Pedmark: 12.5% (100 mL)
Generic: 25% [250 mg/mL] (50 mL)
Yes
Solution (Pedmark Intravenous)
12.5% (per mL): $137.01
Solution (Sodium Thiosulfate Intravenous)
250 mg/mL (per mL): $2.32
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Seacalphyx: 25% [250 mg/mL] (100 mL) [contains disodium edta, sodium metabisulfite]
Generic: 25% [250 mg/mL] (10 mL, 50 mL)
IV: Cyanide poisoning: Administer by IV infusion over 10 to 30 minutes. Decrease rate of infusion in the event of significant hypotension. When used with sodium nitrite, administer sodium nitrite first, followed immediately by the administration of sodium thiosulfate (Ref). If sodium thiosulfate is used in combination with hydroxocobalamin, administer via different IV lines (Ref).
Calciphylaxis (off-label use): Administer by IV infusion over 30 to 60 minutes (Ref).
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 SUBQ (off-label route) into the extravasation site using ≤25-gauge needle; change needle with each injection (Ref).
Cisplatin, concentrated: Inject into the existing IV line; consider also injecting 1 mL as 0.1 mL SUBQ injections (clockwise) into the area around the extravasation using a new 25- or 27-gauge needle for each injection (Ref).
Bendamustine: SUBQ: Bendamustine extravasation may be managed with sodium thiosulfate in the same manner as mechlorethamine extravasation (Ref).
Parenteral: Route of administration dependent upon use.
IV:
Cisplatin-induced ototoxicity: Pedmark (125 mg/mL): Note: Sodium thiosulfate (Pedmark) can cause nausea and vomiting; antiemetics should be administered prior to treatment. Premedication with antihistamines or glucocorticoids (if appropriate) should be administered to patients with a history of hypersensitivity reactions.
Administer undiluted by IV infusion over 15 minutes at 6 hours after end of cisplatin infusion. Note: If cisplatin is a multiday regimen, administer at least 10 hours prior to next cisplatin dose if able; however, if subsequent dose due in <10 hours, do not administer sodium thiosulfate.
Cyanide poisoning: Administer undiluted (25% solution) by IV infusion over 10 to 30 minutes immediately after the administration of sodium nitrite (Ref). Decrease rate of infusion in the event of significant hypotension.
Extravasation management: Cisplatin, concentrated: Inject 1/6 M (~4%) sodium thiosulfate solution into the existing IV line in addition to SUBQ injections around extravasation site (Ref).
SUBQ: Extravasation management: 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 unless treating cisplatin extravasation (for cisplatin extravasation, temporarily keep needle/cannula in place to allow for IV sodium thiosulfate to be administered); elevate extremity.
Mechlorethamine: Inject SUBQ 1/6 M (~4%) sodium thiosulfate solution into the extravasation site using ≤25-gauge needle; change needle with each injection (Ref).
Cisplatin, concentrated: Inject SUBQ 1/6 M (~4%) sodium thiosulfate solution clockwise into the area around the extravasation site using a new 25- or 27-gauge needle for each injection (Ref).
Cyanide poisoning (alternative agent): Treatment of acute, life-threatening cyanide poisoning in combination with sodium nitrite.
Note: The preferred antidote for the treatment of acute cyanide poisoning is hydroxocobalamin, especially in patients who have concurrent carbon monoxide poisoning (eg, smoke inhalation), significant anemia, or G6PD deficiency (Anseeuw 2013). Sodium nitrite and sodium thiosulfate should be considered only if hydroxocobalamin is unavailable, there is a contraindication to the use of hydroxocobalamin, or if the patient has a known sensitivity to hydroxocobalamin or vitamin B12 analogues. Sodium thiosulfate is not generally used as the sole intervention for cyanide toxicity as it has a delayed onset of action, small Vd, and short half-life. Consider consultation with a clinical toxicologist or poison control center.
Ototoxicity: To reduce the risk of ototoxicity associated with cisplatin in pediatric patients ≥1 month of age with localized, nonmetastatic solid tumors.
Limitations of use: Safety and efficacy have not been established when administered following cisplatin infusions longer than 6 hours.
Calciphylaxis; Management of mechlorethamine extravasation; Management of delayed calcium extravasation (calcinosis cutis); Management of concentrated cisplatin (≥0.4 mg/mL) extravasation; Management of bendamustine extravasation
None known.
There are no known significant interactions.
Cyanide crosses the placenta; untreated cyanide poisoning can be fatal to the mother and fetus.
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). However, other treatments may be preferred for the treatment of cyanide toxicity during pregnancy (Culnan 2018; Roderique 2012).
It is not known if sodium thiosulfate is present in breast milk.
Cyanide and thiocyanate (which forms after sodium thiosulfate combines with cyanide) are present in breast milk. Clinicians should be aware that the breastfed infant may have been exposed to cyanide and may also require treatment for cyanide poisoning (De Capitani 2017); consultation with a clinical toxicologist or poison control center is highly recommended. It is not known when breastfeeding may safely be restarted after administration of sodium thiosulfate for the treatment of cyanide poisoning.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer.
Cyanide poisoning: Monitor for at least 24 to 48 hours after administration; BP and heart rate during and after infusion; hemoglobin/hematocrit; co-oximetry; serum lactate levels; venous-arterial PO2 gradient; chloride and anion gap; serum methemoglobin and oxyhemoglobin.
Ototoxicity prevention: Serum potassium and sodium (baseline and as clinically indicated). Monitor for signs and symptoms of hypersensitivity, hypernatremia, and hypokalemia.
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 (Stefanos 2023).
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.
Cisplatin ototoxicity: Neutralizes cisplatin to produce an inactive platinum complex.
Distribution: Vd:
Thiosulfate:
Pediatric patients ≥1 month of age: 0.23 L/kg.
Adults: 0.15 L/kg (Howland 2019).
Thiocyanate: 0.25 L/kg.
Half-life elimination:
Thiosulfate:
Pediatric patients ≥1 month of age: 20 to 50 minutes.
Adults: ~3 hours (Howland 2019).
Thiocyanate: 2.7 days; prolonged with renal impairment to ~9 days.
Excretion:
Pediatric patients ≥1 month of age: Urine (approximately 50% thiosulfate as unchanged drug, >95% within the first 4 hours after administration).
Adults: Urine (~20% to 50% thiosulfate as unchanged drug).
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