Dosing & Uses
Dosage Forms & Strengths
injection solution
- 250mg/mL (25%)
Cyanide Poisoning
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
Sodium Nitrite: 10 mL of sodium nitrite at the rate of 2.5 to 5 mL/minute
Sodium thiosulfate: 50 mL of sodium thiosulfate immediately following administration of sodium nitrite
Airway, ventilatory and circulatory support, and oxygen administration should not be delayed in order to administer sodium nitrite and sodium thiosulfate
If signs of poisoning reappear, repeat treatment using one-half original dose of both sodium nitrite and sodium thiosulfate
Expert advice from a regional poison control center may be obtained by calling 1-800-222-1222
Dosing considerations
- The safety of administering other cyanide antidotes simultaneously with sodium thiosulfate injection has not been established; if a decision is made to administer another cyanide antidote with sodium thiosulfate injection, these drugs should not be administered concurrently in the same intravenous (IV) line
- If clinical suspicion of cyanide poisoning is high, administer sodium thiosulfate injection without delay
- Cyanide poisoning may result from inhalation, ingestion, or dermal exposure to various cyanide-containing compounds, including smoke from closed-space fires
- Sources of cyanide poisoning include hydrogen cyanide and its salts, cyanogenic plants, aliphatic nitriles, and prolonged exposure to sodium nitroprusside
- Presence and extent of cyanide poisoning are often initially unknown
- There is no widely available, rapid, confirmatory cyanide blood test; treatment decisions must be made on basis of clinical history and signs and symptoms of cyanide intoxication
- Symptoms of cyanate poisoning include headache, confusion, dyspnea, chest tightness, nausea
- Signs of cyanide poisoning include altered mental status (eg, confusion, disorientation), seizures or coma, mydriasis, tachypnea/hyperpnea, bradypnea/apnea (late), hypertension (early)/hypotension (late), cardiovascular collapse, vomiting, plasma lactate concentration >8mmol/L
- In some settings, panic symptoms including tachypnea and vomiting may mimic early cyanide poisoning signs; the presence of altered mental status (eg, confusion and disorientation) and/or mydriasis is suggestive of true cyanide poisoning although these signs can occur with other toxic exposures as well
-
Smoke inhalation
- Not all smoke inhalation victims will have cyanide poisoning and may present with burns, trauma, and exposure to other toxic substances making a diagnosis of cyanide poisoning particularly difficult
- Prior to administration of sodium thiosulfate injection, smoke-inhalation victims should be assessed for exposure to fire or smoke in an enclosed area, presence of soot around the mouth, nose, or oropharynx; altered mental status, although hypotension is highly suggestive of cyanide poisoning, it is only present in a small percentage of cyanide-poisoned smoke inhalation victims
- Also indicative of cyanide poisoning is a plasma lactate concentration greater than or equal to 10 mmol/L (a value higher than that typically listed in the table of signs and symptoms of isolated cyanide poisoning because carbon monoxide associated with smoke inhalation also contributes to lactic acidemia); if cyanide poisoning is suspected, treatment should not be delayed in order to obtain a plas
Cisplatin Extravasation (Off-label)
2 mL 1/6 molar solution through IV cannula for every 100 mg cisplatin; remove needle, then inject 0.1 mL injections clockwise around extravasation area up to 1 mL; repeat several times within the 3-4 hr of extravasation incident
Preparation of 1/6 Molar solution: 1.6 mL of 25% solution + 8.4 mL sterile water for injection
Cisplatin Nephrotoxicity (Off-label)
4 g/m² IV bolus followed by 12 g/m² IV infusion over 6 hr
Orphan Designations
Calciphylaxis: 25 g IV 3 times per week following dialysis for 6 weeks to 9 months; other protocols exist
Mechlorethamine extravasation: 2 mL 10% solution through IV cannula for every 2 mg mechlorethamine extravasated; remove needle, then inject 10 mL of 1/6 molar solution SC
Sulfur mustard poisoning
Dermatomyositis
Orphan sponsor
- Hope Pharmaceuticals; 16416 N. 92nd Street, Suite 125; Scottsdale, AZ 85260
Dosage Forms & Strengths
injection solution
- 250mg/mL (25%)
injectable solution
- 12.5g/100mL (single-dose vial; Pedmark)
Cyanide Poisoning
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
Sodium Nitrite: 0.2 mL/kg (6 mg/kg or 6-8 mL/m2 BSA) of sodium nitrite at the rate of 2.5 to 5 mL/minute not to exceed 10 mL
Sodium Thiosulfate: 1 mL/kg of body weight (250 mg/kg or approximately 30-40 mL/m2 of BSA) not to exceed 50 mL total dose immediately following administration of sodium nitrite
If signs of poisoning reappear, repeat treatment using one-half original dose of both sodium nitrite and sodium thiosulfate
Airway, ventilatory and circulatory support, and oxygen administration should not be delayed in order to administer sodium nitrite and sodium thiosulfate
Expert advice of a regional poison control center may be obtained by calling 1-800-222-1222
Dosing considerations
- The safety of administering other cyanide antidotes simultaneously with sodium thiosulfate injection has not been established; if a decision is made to administer another cyanide antidote with sodium thiosulfate injection, these drugs should not be administered concurrently in the same intravenous (IV) line
- If clinical suspicion of cyanide poisoning is high, administer sodium thiosulfate injection without delay
- Cyanide poisoning may result from inhalation, ingestion, or dermal exposure to various cyanide-containing compounds, including smoke from closed-space fires
- Sources of cyanide poisoning include hydrogen cyanide and its salts, cyanogenic plants, aliphatic nitriles, and prolonged exposure to sodium nitroprusside
- Presence and extent of cyanide poisoning are often initially unknown
- There is no widely available, rapid, confirmatory cyanide blood test; treatment decisions must be made on basis of clinical history and signs and symptoms of cyanide intoxication
- Symptoms of cyanate poisoning include headache, confusion, dyspnea, chest tightness, nausea
- Signs of cyanide poisoning include altered mental status (eg, confusion, disorientation), seizures or coma, mydriasis, tachypnea/hyperpnea, bradypnea/apnea (late), hypertension (early)/hypotension (late), cardiovascular collapse, vomiting, plasma lactate concentration >8mmol/L
- In some settings, panic symptoms including tachypnea and vomiting may mimic early cyanide poisoning signs; the presence of altered mental status (eg, confusion and disorientation) and/or mydriasis is suggestive of true cyanide poisoning although these signs can occur with other toxic exposures as well
-
Smoke inhalation
- Not all smoke inhalation victims will have cyanide poisoning and may present with burns, trauma, and exposure to other toxic substances making a diagnosis of cyanide poisoning particularly difficult
- Prior to administration of Sodium Thiosulfate Injection, smoke-inhalation victims should be assessed for exposure to fire or smoke in an enclosed area, presence of soot around the mouth, nose, or oropharynx; altered mental status, although hypotension is highly suggestive of cyanide poisoning, it is only present in a small percentage of cyanide-poisoned smoke inhalation victims
- Also indicative of cyanide poisoning is a plasma lactate concentration greater than or equal to 10 mmol/L (a value higher than that typically listed in the table of signs and symptoms of isolated cyanide poisoning because carbon monoxide associated with smoke inhalation also contributes to lactic acidemia); if cyanide poisoning is suspected, treatment should not be delayed in order to obtain a plasma lactate concentration
Cisplatin-Induced Ototoxicity
Pedmark only
Indicated to reduce the risk of ototoxicity associated with cisplatin in pediatric patients aged 1 month and older with localized, non-metastatic solid tumors
Administer as IV infusion over 15 min starting 6 hr after completing cisplatin infusion
For multiday cisplatin regimens, administer 6 hr after each cisplatin infusion but at least 10 hr before the next cisplatin infusion
Do not start if <10 hr before starting next cisplatin infusion
Dose is based on surface area according to actual body weight (ABW)
- ABW <5 kg: 10 g/m2
- ABW 5-10 kg: 15 g/m2
- ABW >10kg: 20 g/m2
Dosage Modifications
Pedmark
- Grade 3 or 4 hypersensitivity reactions: Permanently discontinue
- Hypernatremia (sodium >145 mmol/L): Withhold until sodium normalizes; resume at same dose
- Grade 3 or 4 hypokalemia: Withhold until potassium normalizes; resume at the same dose
- Grade 3 other adverse reactions: Withhold until Grade ≤1; resume at same dose
- Grade 4 other adverse reactions: Permanently discontinue
Renal impairment
- Sodium thiosulfate is substantially excreted by the kidney
- Mild-to-severe or end-stage renal disease: No dose adjustment necessary
- If GFR decreased to <60 mL/min/1.73m2, monitor for signs and symptoms of hypernatremia and hypokalemia more closely
Dosing Considerations
Not substitutable with other sodium thiosulfate products
Limitations of use
- Safety and efficacy not established when administered following cisplatin infusions >6 hr
- May not reduce the risk of ototoxicity when administered following longer cisplatin infusions, because irreversible ototoxicity may have already occurred
Adverse Effects
>10%
Pedmark and Cisplatin
- Vomiting (85%)
- Nausea (40%)
- Decreased hemoglobin (34%)
- Hypokalemia (15-27%)
- Hypokalemia, Grade 3 or 4 (9-27%)
- Hypernatremia (26%)
- Hypophosphatemia (15-20%)
- Hypophosphatemia, Grade 3 or 4 (9-20%)
- Decreased hemoglobin, Grade 3 or 4 (19%)
- Pyrexia (15%)
- Hyponatremia (14%)
- Stomatitis (14%)
- Stomatitis, Grade 3 or 4 (14%)
- Hyponatremia, Grade 3 or 4 (12%)
- Hypermagnesemia (11%)
1-10%
Pedmark and Cisplatin
- Hypermagnesemia, Grade 3 or 4 (9%)
- Vomiting, Grade 3 or 4 (8%)
- Nausea, Grade 3 or 4 (3.8%)
Frequency Not Defined
Hypotension (infusion rate-dependent)
Nausea/vomiting
Disorientation
Headache
Prolonged bleeding therapy
Hypersensitivity reactions
Contact dermatitis
Warmth
Local irritation
Postmarketing Reports H3
Cardiovascular disorders: Hypertension, hypotension
Metabolic and nutritional disorders: Metabolic acidosis, hypocalcemia
Warnings
Contraindications
None
Pedmark: History of severe hypersensitivity to sodium thiosulfate or any components
Cautions
Hypernatremia and hypokalemia reported; monitor serum sodium and potassium levels at baseline and as needed; do not initiate infusion in patients with baseline serum sodium >145 mmol/L
May cause nausea and vomiting; premedicate patients with antiemetics and provide additional antiemetics and supportive care as appropriate
Hypersensitivity reactions
- Hypersensitivity reactions occurred
- Monitor for hypersensitivity reactions
- Immediately discontinue and institute appropriate care if a hypersensitivity reaction occurs
- Administer antihistamines or glucocorticoids (if appropriate) before each subsequent administration
- May contain sodium sulfite; sulfite exposure can cause hypersensitivity reactions (eg, anaphylactic symptoms, severe asthma episodes) in patients with sulfite sensitivity
Pregnancy & Lactation
Pregnancy
There are no available data on use in pregnant females to establish a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes
There are risks to pregnant woman and fetus associated with untreated cyanide poisoning; if cyanide poisoning is suspected and known, sodium thiosulfate injection for sequential use with sodium nitrite is recommended
Oral or IV administration of sodium thiosulfate during organogenesis resulted in no signs of malformations or lethality, but at doses and exposures that were lower than those in humans
Administered following cisplatin infusions, which can cause embryofetal harm; refer to cisplatin for additional information
Animal data
- In published animal studies, no evidence of embryotoxicity or malformations reported when sodium thiosulfate 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
- Cyanide readily crosses the placenta; cyanide poisoning is a medical emergency in pregnancy, which can be fatal for the pregnant woman and fetus if left untreated; life-sustaining therapy should not be withheld due to pregnancy
Lactation
There are no data on presence of sodium thiosulfate in human or animal milk, effects on breastfed infant, or on milk production; cyanide and thiocyanate (which is formed when sodium thiosulfate combines with cyanide) are present in human milk
Administered following cisplatin infusions; refer to cisplatin for additional information
Because of potential for serious adverse reactions in breastfed infant, breastfeeding not recommended during treatment with sodium thiosulfate injection; there are no data to determine when breastfeeding may be safely restarted following administration of sodium thiosulfate injection
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Thiosulfate is sulfur donor utilized by rhodenase to convert cyanide to less toxic thiocyanate
Extravasation: Neutralizes reactive species of mechlorethamine; reduces formation of hydroxyl radicals that cause tissues injury
Increases solubility of calcium
Pharmacokinetics
Half-life: 3 hr (thiosulfate); 3 days (thiocyanate); 9 days (renal impairment)
Excretion: Urine (20-50%)
Administration
Sodium nitrite injection and sodium thiosulfate injection are administered by slow intravenous injection; they should be given as early as possible after diagnosis of acute life-threatening cyanide poisoning has been established
Sodium nitrite should be administered first, followed immediately by sodium thiosulfate; blood pressure must be monitored during infusion in both adults and children; the rate of infusion should be decreased if significant hypotension noted
In adult and pediatric patients with known anemia, it is recommended that the dosage of sodium nitrite be reduced proportionately to hemoglobin concentration
Visually inspect all parenteral drug products for particulate matter and discoloration prior to administration
Patients should be monitored for at least 24-48 hours after sodium thiosulfate injection 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 presence of methemoglobinemia
Chemical incompatibility reported between sodium thiosulfate injection and hydroxocobalamin; these drugs should not be administered simultaneously through the same IV line; no chemical incompatibility reported between sodium thiosulfate and sodium nitrite when administered sequentially through same IV line
Simultaneous administration of sodium thiosulfate injection and blood products (whole blood, packed red cells, platelet concentrate, and/or fresh frozen plasma) through same intravenous line not recommended; however, blood products and sodium thiosulfate injection can be administered simultaneously using separate intravenous lines (preferably on contralateral extremities, if peripheral lines are being used)
IV Preparation (Pedmark)
Calculate dose and determine number of vial(s) needed
Visually inspect contents of vial(s) for particulate matter and discoloration; discard if discolored or contains visible particulates
Withdraw calculated dose from vial(s) into a syringe or transfer calculated dose into an empty infusion bag
Once drug is withdrawn, use immediately
If not used immediately, may store in an infusion bag for ≤18 hours at 20-22°C (68- 72°F); discard unused portion
No incompatibilities have been observed between sodium thiosulfate with infusion bags made of polyvinyl chloride, ethylene vinyl acetate, or polyolephin
IV Administration (Pedmark)
Infuse over 15 min starting 6 hr after completing cisplatin infusion
For multiday cisplatin regimens, administer 6 hr after each cisplatin infusion but at least 10 hr before the next cisplatin infusion
Do not start if <10 hr before starting next cisplatin infusion
Premedications
- Administer antiemetics before each infusion
- For hypersensitivity reactions, administer antihistamines and glucocorticoids (if appropriate) before each subsequent infusion
Storage
Unopened vials
- Store at 20-25ºC (68-77ºF); excursions are permitted to 15-30ºC (59-86ºF)
Withdraw drug from vials
- Use immediately
- If not used immediately, may store in an infusion bag for ≤18 hours at 20-22ºC (68- 72ºF); discard unused portion
Images
Patient Handout
sodium thiosulfate intravenous
NO MONOGRAPH AVAILABLE AT THIS TIME
USES: Consult your pharmacist.
HOW TO USE: Consult your pharmacist.
SIDE EFFECTS: Consult your pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: Consult your pharmacist.
DRUG INTERACTIONS: Consult your pharmacist.Keep a list of all your medications with you, and share the list with your doctor and pharmacist.
OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.
NOTES: No monograph available at this time.
MISSED DOSE: Consult your pharmacist.
STORAGE: Consult your pharmacist.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.
Information last revised July 2016. Copyright(c) 2023 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Formulary
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