Herbs Nithiodote (Sodium nitrite and sodium thiosulfate) is used in the treatment of acute life-threatening cyanide poisoning. It is packaged as Sodium Nitrite 30 mg/mL Solution for Injection and Sodium Thiosulfate 250 mg/mL Solution for Injection [Ref].

Nithiodote Uses

• Cyanide poisoning:
  • It is indicated for the management of acute life-threatening cyanide poisoning.

Note:

• The primary antidote of acute cyanide poisoning is hydroxocobalamin, especially in patients who have concurrent carbon monoxide poisoning, significant anemia, or G6PD deficiency.
• In case of hypersensitivity, contraindication or unavailability of hydroxocobalamin, sodium nitrite, and sodium thiosulfate is advised.

Sodium nitrite/thiosulfate (Nithiodote) dose in adults:

Nithiodote dose in the treatment of Cyanide poisoning:

In case of cyanide poisoning, sodium nitrite and sodium thiosulfate are given through an IV, and it's crucial to give them in the right order. First, sodium nitrite is administered, then immediately followed by sodium thiosulfate.

The doses for each are:

Sodium Nitrite:

• 300 mg (10 mL of a 3% solution)
• If symptoms come back, the dose can be repeated at half the original amount.

Alternatively, for patients who can't handle too much methemoglobinemia (which can limit oxygen delivery), the dose can be based on their hemoglobin levels:

Sodium Thiosulfate:

• 12.5 g (50 mL of a 25% solution)
• If symptoms return, the dose can be repeated at half the original amount.

After giving these medicines, it's essential to watch the patient closely for 24-48 hours. If symptoms return during this time, both sodium nitrite and sodium thiosulfate can be given again at half the original doses.

Sodium nitrite/thiosulfate (Nithiodote) dose in Childrens

Note: Dosing in pediatric patients expressed in mg/kg, mL/kg, mL/m , use extra precaution.

Nithiodote dose in the treatment of Cyanide poisoning:

For infants, children, and adolescents suffering from cyanide poisoning, sodium nitrite and sodium thiosulfate are administered intravenously. Remember, sodium nitrite should be given first, immediately followed by sodium thiosulfate. Keep a close eye on the patient for 24 to 48 hours after giving the doses. Sodium nitrite is usually stopped if methemoglobin levels go above 30%.

Sodium Nitrite:

• Manufacturer's Labeling: 6 mg/kg (0.2 mL/kg or 6 to 8 mL/m of a 3% solution); maximum dose: 300 mg (10 mL of a 3% solution). If symptoms return, the dose can be repeated at half the original amount.
• Alternate Dosing (Based on Hemoglobin Level):

Sodium Thiosulfate:

• Manufacturer's Labeling: 250 mg/kg (1 mL/kg of a 25% solution); maximum dose: 12.5 g (50 mL of a 25% solution). If symptoms return, repeat both sodium nitrite and sodium thiosulfate at half the original doses.
• Alternate Dosing: 500 mg/kg (2 mL/kg of a 25% solution); maximum dose: 12.5 g (50 mL of a 25% solution). Monitor the patient for 24 to 48 hours; if symptoms return, repeat both sodium nitrite and sodium thiosulfate at half the original doses.

Always follow proper dosing instructions and consult with a healthcare professional for guidance in administering these medications.

Pregnancy Risk Factor C

• Exposure to high levels of sodium nitrite during pregnancy has shown teratogenic effects in humans, but such effects were not observed in studies on animals with sodium nitrite or sodium thiosulfate.
• However, animal studies did reveal embryotoxic and nonteratogenic effects from sodium nitrite.
• The fetus has lower methemoglobin reductase levels compared to adults, making them more susceptible to nitrite-induced prenatal hypoxia.
• While there are no well-controlled studies on the use of Nithiodote (a combination of sodium nitrite and sodium thiosulfate) in pregnant women, generally, antidotes should be considered based on the mother's health and prognosis rather than concerns about teratogenicity.
• If there's a clear need for an antidote, it should be given to pregnant women without withholding it due to fears of birth defects.

Use of sodium thiosulfate and sodium nitrite during breastfeeding

• It's uncertain whether sodium nitrite or sodium thiosulfate passes into breast milk.
• Due to this uncertainty, caution is advised when giving sodium nitrite and sodium thiosulfate to nursing mothers, as their effects on nursing infants are not fully understood.

Nithiodote Dose adjustment in renal disease:

• The manufacturer's instructions do not specify any dosage adjustments for individuals with renal impairment.
• However, it's important to note that both sodium nitrite and sodium thiosulfate are eliminated significantly through the kidneys.
• Therefore, patients with renal impairment may be at an increased risk of experiencing adverse effects.
• Careful monitoring and possibly dose adjustments should be considered in such cases to ensure the safe and effective use of these medications.

Nithiodote Dose adjustment in liver disease:

• The manufacturer's instructions do not include any dosage adjustments for individuals with hepatic impairment.
• Additionally, there haven't been specific studies conducted on the use of sodium nitrite and sodium thiosulfate in patients with liver issues.

Side effects of Sodium Nitrite and sodium thiosulfate (Nithiodote):

• Cardiovascular:
  • Cardiac Arrhythmia
  • Flushing
  • Hypotension
  • Palpitations
  • Syncope
  • Tachycardia
• Central Nervous System:
  • Anxiety
  • Coma
  • Confusion
  • Dizziness
  • Fatigue
  • Headache
  • Numbness
  • Paresthesia
  • Seizure
  • Tingling Of Skin (Injection Site)
• Dermatologic:
  • Diaphoresis
  • Urticaria
• Endocrine & Metabolic:
  • Acidosis
• Gastrointestinal:
  • Abdominal Pain
  • Nausea
  • Vomiting
• Hematologic & Oncologic:
  • Methemoglobinemia
• Neuromuscular & Skeletal:
  • Weakness
• Ophthalmic:
  • Blurred Vision
• Respiratory:
  • Cyanosis
  • Dyspnea
  • Tachypnea

Side effects of Sodium Thiosulfate:

• Cardiovascular:
  • Hypotension
• Central Nervous System:
  • Disorientation
  • Flushing Sensation
  • Headache
  • Salty Taste
• Gastrointestinal:
  • Nausea
  • Vomiting
• Hematologic & Oncologic:
  • Prolonged Bleeding Time

Contraindication to Sodium nitrite and sodium thiosulfate (Nithiodote):

• According to the manufacturer's labeling, there are no contraindications specified for the use of sodium nitrite and sodium thiosulfate.
• This means that there are no absolute reasons stated by the manufacturer that would prohibit their use in individuals under normal circumstances.

Warnings and precautions

Hypotension: [US-Boxed Warning]

• Sodium nitrite carries a significant risk of causing severe hypotension, which can reduce the body's ability to carry oxygen effectively.
• Serious adverse effects may occur even at doses lower than twice the recommended therapeutic dose.
• It's crucial to monitor patients for adequate blood flow and oxygen levels and ensure they are properly hydrated.
• Caution should be exercised when using sodium nitrite in patients where the diagnosis of cyanide poisoning is uncertain or in those with pre-existing conditions that may affect oxygen or cardiovascular function, such as smoke inhalation victims (due to carbon monoxide exposure), anemia, significant blood loss, or cardiac/respiratory issues.
• Patients who may be vulnerable to vasodilation-related injuries should be treated cautiously, and the use of hydroxocobalamin is recommended in such cases.

Methemoglobinemia: [US Boxed Warning]:

• Sodium nitrite carries a significant risk of causing methemoglobin formation, which reduces the blood's ability to carry oxygen effectively.
• Serious adverse effects may occur even at doses lower than twice the recommended therapeutic dose.
• It's essential to monitor patients for adequate blood flow and oxygen levels.
• Caution should be exercised when using sodium nitrite in patients where the diagnosis of cyanide poisoning is uncertain or in those with pre-existing conditions affecting oxygen or cardiovascular function, such as smoke inhalation victims (due to carbon monoxide exposure), anemia, significant blood loss, or cardiac/respiratory issues.
• Patients at higher risk of developing methemoglobinemia, such as those with congenital methemoglobin reductase deficiency, should also be treated cautiously, and the use of hydroxocobalamin is recommended in such cases.
• Additionally, sodium nitrite should be used with caution alongside medications known to cause methemoglobinemia, such as nitroglycerin or phenazopyridine.
• Sodium nitrite is generally stopped if methemoglobin levels exceed 30%.
• Intravenous methylene blue and exchange transfusion are treatment options for severe, life-threatening methemoglobinemia.

Sodium nitrite and sodium thiosulfate: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

Monitoring After Administration:

• Duration: Monitor for at least 24-48 hours after administration.
• Parameters to Monitor:
  • Blood pressure and heart rate during and after infusion.
  • Hemoglobin/hematocrit levels.
  • Co-oximetry to assess different types of hemoglobin.
  • Serum lactate levels to check tissue oxygenation.
  • Venous-arterial PO gradient to evaluate oxygen exchange.
  • Serum methemoglobin and oxyhemoglobin levels.

Additional Notes:

• Pretreatment Cyanide Levels: These levels might help diagnose cyanide poisoning. However, if the patient is very sick, don't wait for lab results before starting sodium nitrite therapy. Time is critical in such cases, so treatment shouldn't be delayed.

How to administer Sodium nitrite and sodium thiosulfate (Nithiodote)?

IV Administration Protocol for Acute Cyanide Poisoning:

• Timing: Administer via slow IV injection as soon as possible after diagnosing acute, life-threatening cyanide poisoning.
• Sequential Administration:
  • Start with sodium nitrite at a rate of 2.5 to 5 mL/minute.
  • Immediately follow with sodium thiosulfate over 10 to 30 minutes.
• Adjustment for Hypotension: If significant hypotension occurs, decrease the infusion rate.
• Simultaneous Administration with Blood Products:
  • If simultaneous administration of blood products is necessary, preferably use separate lines.
  • If peripheral lines are used, consider using contralateral extremities for each infusion.

Mechanism of action of Sodium nitrite and sodium thiosulfate (Nithiodote):

Sodium Nitrite:

• Mechanism of Action: Promotes the formation of methemoglobin, which competes with cytochrome oxidase for the cyanide ion.
• How it Works: Cyanide combines with methemoglobin to form cyano methemoglobin. This process frees up cytochrome oxidase, allowing aerobic metabolism to continue.

Sodium Thiosulfate:

• Mechanism of Action: Acts as a sulfur donor in the rhodanese-catalyzed formation of thiocyanate.
• How it Works: Thiocyanate is much less toxic than cyanide. By providing sulfur, sodium thiosulfate helps convert cyanide to thiocyanate, reducing its toxicity.

Sodium Nitrite:

• Onset: 30-60 minutes
• Peak Effect: Methemoglobinemia occurs around the same time.
• Duration: Methemoglobinemia typically lasts around 55 minutes.
• Metabolism: Metabolized to ammonia and other metabolites.
• Excretion: Around 40% of the drug is excreted unchanged in urine.

Sodium Thiosulfate:

• Half-life Elimination: Thiosulfate: Approximately 3 hours; Thiocyanate: About 3 days; may be prolonged to up to 9 days in cases of renal impairment.
• Excretion: Approximately 20% to 50% of the drug is excreted unchanged in urine.

International Brands of Sodium nitrite and sodium thiosulfate:

• Nithiodote

Sodium nitrite and sodium thiosulfate Brand Names in Pakistan:

No Brands Available in Pakistan.