Thiotab

Approved Indications:

• Cyanide Poisoning (Acute): Used as an antidote, typically as part of a cyanide antidote kit (along with sodium nitrite).
• Calciphylaxis (Calcific Uremic Arteriolopathy): Off-label but widely used in patients with end-stage renal disease (ESRD) receiving dialysis.
• Cisplatin-Induced Toxicity (Off-label): Reduces ototoxicity and nephrotoxicity associated with high-dose cisplatin chemotherapy.
• Extravasation of Chemotherapy Agents: Off-label use to treat tissue damage from certain cytotoxic drugs (e.g., mechlorethamine).

Route: Intravenous (IV) is the most common.
Formulations: Injectable solution.

Adults:

• Cyanide Poisoning:
• Dose: 12.5 g IV over 10 minutes.
• Administered after sodium nitrite.
• Calciphylaxis (off-label):
• Dose: 25 g IV 3 times weekly after hemodialysis.
• Titrate based on response and tolerability.
• Cisplatin Toxicity (off-label):
• Dose: 4 g/m² IV over 15 minutes before and 12 g/m² over 6 hours after cisplatin infusion.

Pediatrics:

• Cyanide Poisoning:
• Dose: 250–500 mg/kg IV over 10 minutes, not exceeding adult dose of 12.5 g.

Special Populations:

• Renal Impairment: Use with caution in ESRD unless treating calciphylaxis. Clearance is reduced; monitor closely.
• Hepatic Impairment: No specific adjustment, but monitor closely due to limited data.

Sodium thiosulfate acts as a sulfur donor that enhances the conversion of toxic cyanide to the much less toxic thiocyanate, which is excreted renally. In calciphylaxis, the drug likely acts as a calcium chelator, antioxidant, and vasodilator, helping to reduce vascular calcification and improve microcirculation. Additionally, it possesses reducing properties that neutralize reactive oxygen species, contributing to tissue protection in oxidative injury.

• Absorption: Not applicable (IV only).
• Distribution: Widely distributed in extracellular fluid.
• Metabolism: Not metabolized; acts chemically on cyanide.
• Elimination: Primarily renal (excreted as thiosulfate and thiocyanate).
• Half-life: Approximately 15 minutes in plasma; longer in renal impairment.
• Onset of Action: Rapid onset within minutes for cyanide detoxification.
• Duration: Effects last as long as thiocyanate is excreted (up to 24 hours).

• Pregnancy: Not classified by FDA. Use only if clearly needed. Limited human data; animal studies are insufficient.
• Lactation: Unknown if excreted in breast milk. Caution advised. Monitor infants for signs of adverse reactions.
• Summary: Use in pregnancy or breastfeeding only if benefits outweigh potential risks. Avoid unless clearly necessary.

• Primary Class: Antidote.
• Sub-class: Cyanide antidote; also used as a calcium-chelating agent in calciphylaxis.

• Known hypersensitivity to sodium thiosulfate or any of its components.
• Severe fluid or electrolyte imbalance where IV sodium load may worsen the condition.
• Caution in severe renal dysfunction unless treating calciphylaxis under monitoring.

• Renal Dysfunction: Accumulation of thiocyanate can occur; monitor levels if used long term.
• Fluid Overload: High IV volumes may cause fluid retention in susceptible patients (e.g., heart failure).
• Electrolyte Imbalance: Monitor sodium levels and acid-base status.
• Hypotension: Rapid administration may cause hypotension.
• Monitoring Required: Renal function, electrolytes, acid-base balance, and clinical response in calciphylaxis.

Common:

• Gastrointestinal: Nausea, vomiting, abdominal pain.
• Dermatologic: Rash, pruritus.

Serious:

• Metabolic: Hypernatremia, metabolic acidosis.
• Cardiovascular: Hypotension (rapid infusion).
• Neurological: Headache, dizziness, seizures (from thiocyanate accumulation, especially in renal failure).
• Electrolyte: Volume overload, hyponatremia or hypernatremia.

Rare:

• Anaphylactic reactions.
• Severe metabolic disturbances.

Onset: Acute symptoms (e.g., hypotension) can occur during or shortly after infusion; others develop over days to weeks in prolonged therapy.

• Cisplatin: May reduce nephrotoxicity and ototoxicity; beneficial when used with proper timing.
• Nitrates & Nitrites: Part of cyanide antidote kit; must be sequenced properly to avoid methemoglobinemia complications.
• Drugs affecting renal excretion (e.g., NSAIDs): May reduce thiocyanate clearance.
• Food/Alcohol: No known significant interactions.

Metabolic Interactions:

• Not metabolized by CYP450 enzymes; minimal hepatic interaction risk.

• FDA & EMA (Recent Years): Recognized off-label use in calciphylaxis has increased; clinical trials ongoing.
• NCCN Guidelines: Recommend consideration of sodium thiosulfate for cisplatin protection in pediatric and adult oncology settings.
• Renal Guidelines (KDIGO): Support its use in calciphylaxis with appropriate dialysis monitoring.

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C.
• Protection: Protect from light; keep in original container until use.
• Handling: Do not freeze. Discard unused portion after opening.
• Stability: Check expiry before use. Use immediately after dilution if applicable.