Adult Dosing

Life-threatening acute cyanide poisoning

• Sodium nitrite: 10 mL of a 3% solution (300 mg) IV at the rate of 2.5-5 mL/min; then immediately inject sodium thiosulfate 50 mL of a 25% solution (12500 mg) IV

• Note:

• Repeat treatment using one-half the original dose of both components on reappearance of signs of cyanide poisoning
• In patients with known anemia, reduce the dosage of sodium nitrite in proportion to the hemoglobin concentration
• Monitor blood pressure during the course of treatment; reduce the rate of infusion if there is significant hypotension
• Closely monitor methemoglobin levels during the course of treatment and maintain below 30%; discontinue sodium nitrite administration if methemoglobin levels >30%

Pediatric Dosing

Life-threatening acute cyanide poisoning

• Sodium nitrite: 0.2 mL/kg of a 3% solution (6 mg/kg) or 6-8 mL (180 mg-240 mg)/m² BSA at the rate of 2.5-5 mL/min; Max 10 mL (300 mg); then immediately inject sodium thiosulfate 1 mL/kg of a 25% solution (250 mg/kg) or approximately 30-40 mL (7500 mg-10000 mg)/m² of BSA; Max 50 mL (12500 mg)

• Note:

• Repeat treatment using one-half the original dose of both components on reappearance of signs of cyanide poisoning
• In patients with known anemia, reduce the dosage of sodium nitrite in proportion to the hemoglobin concentration
• Monitor blood pressure during the course of treatment; reduce the rate of infusion if there is significant hypotension
• Closely monitor methemoglobin levels during the course of treatment and maintain below 30%; discontinue sodium nitrite administration if methemoglobin levels >30%

[Outline]

• Adult Dosing
• Pediatric Dosing

• Treatment of life-threatening acute cyanide poisoning

Note:

• Carefully weigh the potentially life-threatening risks associated with the therapy against the potential benefits, if the diagnosis of cyanide poisoning is uncertain

• Hypersensitivity to any of the ingredients of the product

• Sodium nitrite has been associated with serious adverse reactions and death, even at doses less than twice the recommended therapeutic dose. Life-threatening hypotension and methemoglobin formation, associated with sodium nitrite component of this drug, may occur concurrently or separately. Use this treatment for acute life-threatening cyanide poisoning and exercise caution in patients where the diagnosis of cyanide poisoning is uncertain
• Closely monitor patients to ensure adequate perfusion and oxygenation during treatment with sodium nitrite. Consider alternative therapeutic approaches in patients known to have diminished oxygen or CV reserve (e.g., smoke inhalation victims, cardiac or respiratory compromise, pre-existing anemia) and those at higher risk of developing methemoglobinemia (e.g., congenital methemoglobin reductase deficiency), as they are more susceptible for potentially life-threatening adverse events related to sodium nitrite component

Renal Dose Adjustment

• Renal impairment: Caution advised; dose adjustments not defined

Hepatic Dose Adjustment

• Hepatic impairment: Dose adjustments not defined

See Supplemental Patient Information

• Severe hypotension, methemoglobinemia, and death have been reported with sodium nitrite, even at doses less than twice the recommended therapeutic dose. Life-threatening hypotension and methemoglobin formation, associated with sodium nitrite component of this drug, may occur concurrently or separately. Use this treatment for acute, life-threatening cyanide poisoning and exercise caution in patients where the diagnosis of cyanide poisoning is uncertain. Exercise caution if the patient is known or suspected to have diminished oxygen or cardiovascular reserve [US Black Box Warning]
• Closely monitor patients to ensure adequate perfusion and oxygenation during treatment with sodium nitrite. Monitor methemoglobin levels and administer oxygen during sodium nitrite treatment whenever possible. Closely monitor hemodynamics during and after administration of sodium nitrite and sodium thiosulfate; decrease infusion rates if hypotension occurs
• Patients with anemia are more susceptible for formation of methemoglobin; administer sodium nitrite dose that is reduced in proportion to their oxygen carrying capacity in such patients
• In patients undergoing treatment with this drug, monitor oxyhemoglobin and methemoglobin levels by pulse oximetry or other measurements. Potential for worsening hypoxia exists in patients with smoke inhalation injury; monitor carboxyhemoglobin and oxyhemoglobin levels in patients having evidence of smoke inhalation. Reduce the sodium nitrite dose in proportion to the oxygen carrying capacity
• During therapy, neonates and infants may be more prone to severe methemoglobinemia compared to adults and older pediatric patients; follow reduced dosing guidelines in pediatric patients
• Consider alternative therapeutic approaches in patients with G6PD deficiency, as they are at higher risk for development of a hemolytic crisis. Monitor patients with known or suspected G6PD deficiency for an acute drop in hematocrit; exchange transfusion may be essential for patients with G6PD deficiency receiving sodium nitrite
• Trace impurities of sodium sulfite may be present in sodium thiosulfate drug product. Presence of a trace amount of sulfites should not deter administration of the drug for treatment of emergency situations, even if the patient is sulfite-sensitive
• Exercise caution when administering other cyanide antidotes simultaneously with sodium nitrite/sodium thiosulfate therapy

Cautions: Use cautiously in

• Renal impairment
• Impaired cardiac function
• Impaired pulmonary function
• Anemia
• Concomitant use with drugs that induce methemoglobinemia
• Concomitant antihypertensive medications
• Co-administration of diuretics or volume depletion due to diuretics
• Concomitant use of drugs known to increase vascular nitric oxide
• Patients susceptible to injury from vasodilation and related hemodynamic sequelae
• Smoke inhalation injury
• Carbon monoxide poisoning
• Uncertain cyanide poisoning
• Patients <6 months of age
• Geriatric patients

Supplemental Patient Information

• Inform patients of the possibility of life-threatening hypotension and methemoglobin formation
• Inform patients of the need for close monitoring of blood pressure and oxygenation

Pregnancy Category:C

Breastfeeding: Safety unknown; manufacturer advises caution.

• CV: Syncope, severe hypotension, tachycardia, palpitations, arrhythmias, dysrhythmia
• HEMA: Methemoglobinemia, prolonged bleeding time
• CNS: Headache, dizziness, seizures, confusion, coma, disorientation, anxiety, lightheadedness
• NEURO: Generalized numbness, tingling
• EENT: Blurred vision
• GI: Nausea, vomiting, abdominal pain, salty taste
• RESP: Tachypnea, dyspnea
• LOCAL: Injection site tingling
• DERM: Cyanosis, urticaria, diaphoresis, warm sensation
• MISC: Acidosis, fatigue, weakness

Sodium nitrite

• Antidote, nitrate; binds to cyanide ions, reacts with hemoglobin to form methemoglobin (low toxicity)
• Well absorbed
• Metabolism: Unknown
• Excreted in urine (40% unchanged)
• Half-life: Unknown

Sodium thiosulfate

• Antidote; catalyzes formation of thiocyanate from cyanide
• Metabolism: Unknown
• Excreted in urine (20-50% unchanged)
• Half-life: 182 min

US Trade Name(s)

• Nithiodote

US Availability

Nithiodote (sodium nitrite/sodium thiosulfate)

• INJ: 30 mg/mL (10 mL vial)/250 mg/mL (50 mL vial)

Canadian Trade Name(s)

• N/A

Canadian Availability

• N/A

UK Trade Name(s)

• N/A

UK Availability

• N/A

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

[Outline]

Emergency/Critical Care

Antidotes; Combination