Regulatory Decision Summary for SODIUM NITRITE INJECTION USP

Based on scientific and clinical evidence, Health Canada considers that the clinical benefits of Sodium Nitrite Injection USP for the treatment of acute cyanide poisoning that is judged to be life-threatening outweigh the potential risks.

Estimation of Benefits

Cyanide poisoning is rapidly fatal and those affected seldom survive many hours. The prevention of death demands a quick diagnosis and the prompt use of specific antidotes. Due to ethical considerations, traditional clinical trials cannot be conducted that would meet the safety and efficacy standards set out in the Food and Drug Regulations. Exposing human subjects to the causative chemical substance cyanide may be lethal or permanently disabling and the circumstances under which cyanide exposure may occur are unpredictable, sporadic and infrequent. Therefore, the clinical benefit was estimated based on submitted literature-based studies and the well-established use of sodium nitrite and sodium thiosulfate with an acceptable level of safety and efficacy for the treatment of acute cyanide poisoning.

As is the case for most antidotes, the clinical use of sodium nitrite is based on animal experiments and extrapolations made from a number of clinical cases. Animal studies demonstrate the greater effectiveness of sodium nitrite when used together with sodium thiosulfate for the treatment of cyanide poisoning. The potentiated activity of the combination therapy antagonizes a considerably larger mean lethal dose of cyanide compared to the use of either drug product administered individually. Overall, the effectiveness of Sodium Nitrite Injection USP (30 mg/mL) as a cyanide antidote is supported when administered sequentially with sodium thiosulfate, producing a marked increase in cyanide antagonism, thereby representing a potentially life-saving means to detoxify larger exposures to cyanide.

Estimation of Risks

Based on the data submitted to support the proposed indication, Sodium Nitrite Injection USP causes hypotension and methemoglobin formation, which diminishes oxygen carrying capacity in the blood. Because of these risks, Sodium Nitrite Injection USP should only be used to treat acute life-threatening cyanide poisoning and should be used with caution in patients where the diagnosis of cyanide poisoning is uncertain. Sodium Nitrite Injection USP should also be used with caution in patients with

1. anemia;
2. impaired renal function;
3. smoke inhalation injury or carbon monoxide poisoning; and
4. glucose-6-phosphate dehydrogenase deficiency.

Neonates and infants may be more susceptible than adults and older pediatric patients to severe methemoglobinemia when Sodium Nitrite Injection USP is administered. Reduced dosing recommendations based on body weight should be followed in pediatric patients. For more information, refer to the Sodium Nitrite for Injection USP Product Monograph approved by Health Canada.

Overall, the clinical benefit of survival clearly outweighs the potential risks of Sodium Nitrite Injection USP for the treatment of acute cyanide poisoning.