Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Treatment of cyanide poisoning must include immediate attention to airway patency, adequacy of oxygenation and hydration, cardiovascular support, and management of seizures. Consideration must be given to decontamination measures based on the route of exposure.
Sodium nitrite does not substitute oxygen therapy and must not delay the set up of the above measures.
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/or signs and symptoms of cyanide intoxication.


Cyanide poisoning may result from exposure to smoke from closed space fires, inhalation, ingestion, or dermal exposure. Sources of cyanide poisoning include hydrogen cyanide and its salts, cyanogens, including cyanogenic plants, aliphatic nitriles, or prolonged exposure to sodium nitroprusside.
Signs and symptoms of cyanide poisoning
Common signs and symptoms of cyanide poisoning include: nausea, vomiting, headache, altered mental status (e.g. confusion, disorientation), chest tightness, dyspnoea, tachypnoea or hyperpnoea (early), bradypnoea or apnoea (late), hypertension (early) or hypotension (late), cardiovascular collapse, seizures or coma, mydriasis, and plasma lactate concentration > 8 mmol/L.
In the setting of multiple casualties such as terrorism or chemical disaster, panic symptoms including tachypnoea and vomiting may mimic early cyanide poisoning signs. The presence of altered mental status (confusion and disorientation) and/or mydriasis is suggestive of true cyanide poisoning.
Smoke inhalation
Not all smoke inhalation victims necessarily will have cyanide poisoning, but may present with burns, trauma, and exposure to additional toxic substances aggravating the clinical picture. Before sodium nitrite is administered, it is recommended to check affected persons for the presence of the following:
• exposure to fire smoke in an enclosed area
• soot present around mouth, nose and/or oropharynx
• altered mental status In this setting hypotension and/or a plasma lactate concentration ≥ 10 mmol/L (higher than the one mentioned under signs and symptoms due to the fact that carbon monoxide contributes to lactic acidaemia) are highly suggestive of cyanide poisoning.
In the presence of the above signs, treatment with sodium nitrite must not be delayed to obtain a plasma lactate concentration.


Sodium Nitrite
Sodium nitrite has been associated with severe hypotension, methemoglobinemia, and death at doses less than twice recommended therapeutic doses. When the diagnosis of cyanide poisoning is uncertain and/or the patient is not in extremis, special consideration should be given to administration of sodium nitrite if the patient is known or suspected to have diminished oxygen or cardiovascular reserve (e.g., smoke inhalation victims, pre-existing anaemia, substantial blood loss, cardiac or respiratory compromise) or to be at higher risk of developing methemoglobinemia (e.g., congenital methemoglobin reductase deficiency).
4.4.1 Hypotension
Hemodynamics should be monitored closely during and after administration of sodium nitrite, and infusion rates should be slowed if hypotension occurs. Sodium nitrite should be used with caution in the presence of other drugs that can reduce blood pressure.
4.4.2 Methemoglobinemia
In the presence of nitrites, hemoglobin is converted to methemoglobin, which has a higher binding affinity for cyanide than cytochrome oxidase. If methemoglobinemia becomes excessive (>40%) the effect of the antidote is negated as oxygen transport to the tissue is significantly impaired.
Sodium nitrite should be used with caution in persons with smoke inhalation injury or carbon monoxide poisoning because of the potential for worsening hypoxia due to methemoglobin formation.
Methemoglobin levels should be monitored and oxygen administered during treatment with sodium nitrite whenever possible. When sodium nitrite is administered to humans a wide range of methemoglobin concentrations occur. Methemoglobin concentrations as high as 58% have been reported after two 300-mg doses of sodium nitrite administered to an adult. Sodium nitrite should be used with caution in the presence of other drugs that may cause methemoglobinemia such as procaine and nitroprusside.
4.4.3 Anaemia
Sodium nitrite should be used with caution in adult patients with known anaemia.
Adult patients with anaemia will form more methemoglobin (as a percentage of total hemoglobin) than persons with normal red blood cell (RBC) volumes. Optimally, these patients should receive a sodium nitrite dose that is reduced in proportion to their oxygen carrying capacity. The table below outlines a dosage regimen as a function of haemoglobin concentration. The dose may be increased to achieve the desired effect. A maximum dose of 300 mg (10 mL of a 3% solution) is recommended.

Adult Patients: Maximum initial dose of sodium nitrite according to haemoglobin level.

Haemoglobin     Maximum         Maximum
(g/L)          Initial         Initial
Dose          Dose 3%
Sodium          Sodium
Nitrite         Nitrite
(mg)         Solution
(mL)
70            153             5.1
80            174             5.8
90            195             6.5
100           216             7.2
110           237             7.9
120           258             8.6
130           179             9.3
140           300             10


4.4.4 Paediatric Patients
Neonates and infants may be more susceptible than adults and older paediatric patients to severe methemoglobinemia when sodium nitrite is administered. Reduced dosing guidelines should be followed in paediatric patients based on weight and haemoglobin concentration. For children under 25 kg, where anaemia is suspected, it is recommended that the dose of sodium nitrite be reduced relative to the haemoglobin measurement. The table below outlines a dosage regimen as a function of haemoglobin concentration.



Children under 25 kg: Maximum initial dose of sodium nitrite according to haemoglobin level.

Haemoglobin       Maximum         Maximum
(g/L)            Initial         Initial
Dose          Dose 3%
Sodium          Sodium
Nitrite        Nitrite
(mg/kg)        Solution
(mL/kg)
70              5.8             0.19
80              6.6             0.22
90              7.5             0.25
100             8.8             0.27
110             9.1             0.3
120              10             0.33
130             10.8            0.36
140             11.6            0.39



4.4.5 G6PD Deficiency
Because patients with G6PD deficiency are at increased risk of a hemolytic crisis with sodium nitrite administration, alternative therapeutic approaches should be considered in these patients. Patients with known or suspected G6PD deficiency should be monitored for an acute drop in hematocrit. Exchange transfusion may be needed for patients with G6PD deficiency who receive sodium nitrite.
Sodium Thiosulfate
Sodium thiosulfate drug product may contain trace impurities of sodium sulfite. The presence of a trace amount of sulfites in this product should not deter administration of the drug for treatment of emergency situations, even if the patient is sulfite- sensitive.
Each 12.5 g dose of sodium thiosulfate contains approximately 3.6 g of sodium, 115 mg of potassium, and 140 mg of boric acid.

Effects on Driving

4.7   Effects on ability to drive and use machines
Not relevant.