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:

Note:

Intravenous sodium nitrite followed by the administration of sodium thiosulfate.

• Sodium nitrite:

  • 300 mg (10 mL of a 3% solution); may repeat at one-half of the original dose if symptoms of cyanide toxicity return

Dosing is based on hemoglobin levels in patients who are unable to tolerate significant methemoglobinemia such as heart/lung disease with inefficient oxygen delivery.

• Sodium thiosulfate:

  • 5 g (50 mL of a 25% solution).
  • The dose may be repeated at one-half the original dose if symptoms of cyanide toxicity return

Note:

Monitor the patient for 24-48 hours, Half amount of original dose is repeated for both sodium nitrite and sodium thiosulfate in returning symptoms.

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:

Note: Monitor the patient for 24 to 48 hours following doses. If methemoglobin levels >30%, therapy should be stopped.

• Sodium nitrite:

  • Manufacturer's labeling:

    • 6 mg/kg (0.2 mL/kg or 6 to 8 mL/m of a 3% solution) intravenous
    • The maximum dose is 300 mg (10 mL of a 3% solution)
    • The dose may be repeated at one-half the original dose if symptoms of cyanide toxicity return

  • Alternate dosing:

    •  Dosing is based on hemoglobin levels in patients who are unable to tolerate significant methemoglobinemia such as heart/lung disease with inefficient oxygen delivery.

• Sodium thiosulfate:

  • Manufacturer's labeling:

    • 250 mg/kg (1 mL/kg of a 25% solution) intravenous
    • maximum dose 12.5 g (50 mL of a 25% solution).

  • Alternate dosing:

    • 500 mg/kg (2 mL/kg of a 25% solution) intravenous
    • maximum dose: 12.5 g (50 mL of a 25% solution).
    • Monitor the patient for 24-48 hours.
    • Half amount of original dose is repeated for both sodium nitrite and sodium thiosulfate in returning symptoms.

Pregnancy Risk Factor C

• Teratogenicity can be caused by sodium nitrite in humans.
• Studies on animal reproduction showed that embryotoxic and non-teratogenic effects were observed.
• The fetal Methemoglobin Reductase Level is low and can lead to prenatal hypoxia.
• If there is a clear indication, antidotes may be used during pregnancy. However, they should not be withheld due to fears of teratogenicity.

Use of sodium thiosulfate and sodium nitrite during breastfeeding

• Excretions of sodium thiosulfate or sodium nitrite in breast milk are unknown.
• The manufacturer suggests that nursing mothers be cautious when giving sodium thiosulfate and sodium nitrite to their babies.

Nithiodote Dose adjustment in renal disease:

No dosage adjustment provided in manufacturer’s labeling but the risk of adverse effects may be increased in renal impairment.

Nithiodote Dose adjustment in liver disease:

No dosage adjustment provided in the manufacturer’s labeling.

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):

The manufacturer's labeling does not contain any contraindications.

Warnings and precautions

• Hypotension: [US-Boxed Warning]

  • Hypotension can be caused by sodium nitrite. This may lead to diminished oxygen-carrying ability. Therefore, it is important to monitor oxygenation and perfusion closely.
  • Hydroxocobolamin is recommended in cases of anemia and excessive blood loss. It also works well in patients who are susceptible to vasodilation injury.

• Methemoglobinemia: [US Boxed Warning]:

  • Methemoglobinemia can be caused by sodium nitrite, which may lead to decreased oxygen-carrying ability.
  • Therefore, it should be stopped if methemoglobin levels are greater than 30 percent
  • The life-threatening condition can be treated with intravenous methyleneblue or exchange transfusion.
  • Avoid mixing methemoglobinemia-causing medications (eg, nitroglycerin, or phenazopyridine).

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 is required for

• BP
• Pulse
• Hb/hematocrit
• Pre treatment cyanide levels
• serum methemoglobin and oxyhemoglobin
• serum lactate levels
• venous-arterial PO gradient.

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

• It should be given immediately in acute, life-threatening cyanide poisoning.
• Administer sodium nitrite first at a rate of 2.5 to 5 mL/minute intravenously, followed immediately by sodium thiosulfate over 10 to 30 minutes.
• If hypotension develops, the infusion rate should be reduced. Other blood products should be given using separate lines.

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

Methemoglobin production is enhanced by sodium nitrite, which competes for the cyanide Ion. Cyanide is combined with methemoglobin and forms cyano methemoglobin. This allows aerobic metabolism to continue.

Sodium Thiosulfate It is used as a sulfur donor during the rhodanese catalyzed production of thiocyanate, which is less toxic that cyanide.

Sodium nitrite:

Onset:

Peak effect: Methemoglobinemia: 30-60 minutes

Duration: Methemoglobinemia: 55 minutes

Metabolism: To ammonia and other metabolites

Excretion: Occurs in urine (40% as unchanged drug)

Sodium thiosulfate:

Half-life elimination:

• Thiosulfate: 3 hours
• Thiocyanate: 3 days
• Renal impairment: ≤9 days

Excretion: Occurs in urine (20% to 50% as unchanged drug)

International Brands of Sodium nitrite and sodium thiosulfate:

• Nithiodote

Sodium nitrite and sodium thiosulfate Brand Names in Pakistan:

No Brands Available in Pakistan.