Sodium nitrite and Sodium thiosulfate

NITHIODOTE is indicated for the treatment of acute cyanide poisoning that is judged to be serious or life-threatening. When the diagnosis of cyanide poisoning is uncertain, carefully weigh the potentially life-threatening risks associated with NITHIODOTE against the potential benefits, especially if the patient is not in extremis. NITHIODOTE, an antidote, is indicated for the treatment of acute cyanide poisoning that is judged to be serious or life-threatening. Use with caution if the diagnosis of cyanide poisoning is uncertain.

Cyanide is an extremely toxic poison. In the absence of rapid and adequate treatment, exposure to a high dose of cyanide can result in death within minutes due to the inhibition of cytochrome oxidase resulting in arrest of cellular respiration. Specifically, cyanide binds rapidly with cytochrome a3, a component of the cytochrome c oxidase complex in mitochondria. Inhibition of cytochrome a3 prevents the cell from using oxygen and forces anaerobic metabolism, resulting in lactate production, cellular hypoxia and metabolic acidosis. In massive acute cyanide poisoning, the mechanism of toxicity may involve other enzyme systems as well. Signs and symptoms of acute systemic cyanide poisoning may develop rapidly within minutes, depending on the route and extent of cyanide exposure.

If clinical suspicion of cyanide poisoning is high, administer NITHIODOTE without delay and in conjunction with appropriate airway, ventilatory, and circulatory support. The expert advice of a regional poison control center may be obtained by calling 1-800-222-1222. Dosing: Age Intravenous Dose of Sodium Nitrite and Sodium Thiosulfate Adults 1) Sodium Nitrite -10 mL of sodium nitrite at the rate of 2.5 to 5 mL/minute 2) Sodium Thiosulfate - 50 mL of sodium thiosulfate immediately following administration of sodium nitrite. Children 1) Sodium Nitrite - 0.2 mL/kg (6 mg/kg or 6-8 mL/m 2 BSA) of sodium nitrite at the rate of 2.5 to 5 mL/minute not to exceed 10 mL 2) Sodium Thiosulfate - 1 mL/kg of body weight (250 mg/kg or approximately 30-40 mL/m 2 of BSA) not to exceed 50 mL total dose immediately following administration of sodium nitrite.

None None.

Boxed warning (life threatening hypotension and methemoglobin formation): Sodium nitrite can cause serious adverse reactions and death in humans, even at doses less than twice the recommended therapeutic dose. Sodium nitrite causes hypotension and methemoglobin formation, which diminishes oxygen carrying capacity. Hypotension and methemoglobin formation can occur concurrently or separately. Methemoglobinemia: Sodium nitrite reacts with hemoglobin to form methemoglobin and should be used with caution in patients known to have anemia. Monitor oxyhemoglobin and methemoglobin levels by pulse co-oximetry or other measurements. Optimally, the sodium nitrite dose should be reduced in proportion to the oxygen carrying capacity. Smoke inhalation: Carbon monoxide contained in smoke can result in the formation of carboxyhemoglobin that can reduce the oxygen carrying capacity of the blood.

There have been no controlled clinical trials conducted to systematically assess the adverse events profile of sodium nitrite or sodium thiosulfate. The medical literature has reported the following adverse events in association with sodium nitrite or sodium thiosulfate administration. These adverse events were not reported in the context of controlled trials or with consistent monitoring and reporting methodologies for adverse events. Therefore, frequency of occurrence of these adverse events cannot be assessed. Most common adverse reactions are: Sodium nitrite: syncope, hypotension, tachycardia, palpitations, dysrhythmia, methemoglobinemia, headache, dizziness, blurred vision, seizures, confusion, coma. Sodium thiosulfate: hypotension, headache, disorientation.

Formal drug interaction studies have not been conducted with NITHIODOTE.

Store at controlled room temperature between 20°C and 25°C (68°F - 77°F), excursions permitted to 15-30°C (59 to 86°F). Do not freeze. Protect from direct light.