Sodium Nitrite

Sodium nitrite is indicated for sequential use with sodium thiosulfate for the treatment of acute cyanide poisoning that is judged to be life-threatening. When the diagnosis of cyanide poisoning is uncertain, the potentially life- threatening risks associated with sodium nitrite should be carefully weighed against the potential benefits, especially if the patient is not in extremis.

4). Consideration should be given to official guidelines for the treatment of cyanide intoxication.

Posology For intravenous use. For single use only. 5 g) of sodium thiosulfate (rate of 5 mL/minute). Special populations Older people No specific dose adjustment is required in elderly patients (aged > 65 years). 5 to 5 mL/minute) not to exceed 50 mL total dose of sodium thiosulfate.

NOTE:

If no treatment response is observed within 30 to 60 minutes or if signs of poisoning reappear, repeat treatment after 30 minutes of initial administration using one-half the original dose of both sodium nitrite and sodium thiosulfate.

4). Renal and hepatic impairment Although the safety and efficacy of sodium nitrite have not been studied in patients with renal and hepatic impairments, sodium nitrite is administered as emergency therapy in an acute, life-threatening situation only and no dose adjustment is required in these patients.

Method of administration Comprehensive treatment of acute cyanide intoxication requires support of vital functions. Supportive care alone may be sufficient treatment without administration of antidotes for many cases of cyanide intoxication, particularly in conscious patients without signs of severe toxicity.

Administration of cyanide antidotes should be considered adjunctive to appropriate supportive therapies such as airway, ventilatory, and circulatory support. Supportive therapies, including oxygen administration, should not be delayed to administer cyanide antidotes.

Sodium nitrite injection and sodium thiosulfate injection are administered by slow intravenous injection. Cyanide antidotes should be given as early as possible after a diagnosis of acute life-threatening cyanide poisoning has been established.

Sodium thiosulfate may be administered soon after prior treatment with a fast-acting cyanide antidote such as sodium nitrite or hydroxocobalamin. Blood pressure must be monitored during infusion in both adults and children. The rate of infusion should be decreased if significant hypotension is noted.

All parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration, whenever solution and container permit.

There have been no controlled clinical trials conducted to systematically assess the adverse events profile of sodium nitrite. The medical literature has reported the following adverse events in association with sodium nitrite 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. System organ class Frequency Undesirable effect Cardiac and vascular disorders Not known Syncope, hypotension*, tachycardia, , palpitations, dysrhythmia* Blood and lymphatic system disorders Not known Methemoglobinemia* Nervous system disorders Not known Headache, dizziness, blurred vision, seizures, confusion, coma* Gastrointestinal disorders Not known Nausea, vomiting, abdominal pain Respiratory, thoracic and mediastinal disorders Not known Tachypnea, dyspnea Skin disorders Not known Urticaria General disorders and administration site conditions Not known Anxiety, diaphoresis, lightheadedness, injection site tingling, cyanosis, acidosis, *Description of selected adverse reactions Severe hypotension, methemoglobinemia, cardiac dysrhythmias, coma and death have been reported in patients without life-threatening cyanide poisoning but who were treated with injection of sodium nitrite at doses less than twice those recommended for the treatment of cyanide poisoning.

uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

1.

18 Page 3 of 22 SODIUM NITRITE INJECTION, USP 30 mg/mL PART I: HEALTH PROFESSIONAL INFORMATION HEALTH CANADA HAS AUTHORIZED THE SALE OF THIS EXTRAORDINARY USE NEW DRUG FOR THE TREATMENT OF CYANIDE POISONING THAT IS JUDGED TO BE LIFE-THREATENING BASED ON LIMITED CLINICAL TESTING IN HUMANS SUMMARY PRODUCT INFORMATION Route of Administration Dosage Form / Strength Clinically Relevant Nonmedicinal Ingredients Intravenous Sodium nitrite injection, USP, 30 mg/mL None For a complete listing see Dosage Forms, Composition and Packaging section.

INDICATIONS AND CLINICAL USE Sodium Nitrite Injection is indicated for sequential use with sodium thiosulfate for the treatment of acute cyanide poisoning that is judged to be life-threatening. When the diagnosis of cyanide poisoning is uncertain, the potential risks associated with Sodium Nitrite Injection should be carefully weighed against the potential benefits, especially if the patient is not in extremis.

Cyanide poisoning may result from inhalation, ingestion, or dermal exposure to various cyanide- containing compounds, including smoke from closed-space fires. Sources of cyanide poisoning include hydrogen cyanide and its salts, cyanogenic plants, aliphatic nitriles, and prolonged exposure to sodium nitroprusside.

The presence and extent of cyanide poisoning are often initially unknown. There is no widely available, rapid, confirmatory cyanide blood test. Treatment decisions must be made on the basis of clinical history and signs and symptoms of cyanide intoxication.

If clinical suspicion of cyanide poisoning is high, Sodium Thiosulfate Injection and Sodium Nitrite Injection should be administered without delay. Page 4 of 22 Table 1. , confusion, disorientation)  Seizures or Coma  Mydriasis  Tachypnea/Hyperpnea (early)  Bradypnea/Apnea (late)  Hypertension (early)/ Hypotension (late)  Cardiovascular Collapse  Vomiting  Plasma Lactate Concentration ≥ 8 mmol/L In some settings, panic symptoms including tachypnea and vomiting may mimic early cyanide poisoning signs.

, confusion and disorientation) and/or mydriasis is suggestive of true cyanide poisoning although these signs can occur with other toxic exposures as well. CONTRAINDICATIONS None. WARNINGS AND PRECAUTIONS 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. Because of these risks, sodium nitrite should be used to treat acute life-threatening cyanide poisoning and be used with caution in patients where the diagnosis of cyanide poisoning is uncertain.

Patients should be closely monitored to ensure adequate perfusion and oxygenation during treatment with sodium nitrite. g. g. congenital methemoglobin reductase deficiency) as they are at greater risk for potentially life-threatening adverse events related to the use of sodium nitrite.

Hypotension Sodium nitrite has been associated with severe hypotension, methemoglobinemia, and death at doses less than twice recommended therapeutic doses. Hypotension may occur concurrently or Page 5 of 22 separately. Sodium nitrite should be used to treat life-threatening cyanide poisoning.

, smoke inhalation victims, […]