SODIUM NITRITE Solutions for injection Ref.[9527] Active ingredients: 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).

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.

Methemoglobinemia

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.

Anaemia

Sodium nitrite should be used with caution in patients with known anaemia. 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.

Smoke Inhalation Injury

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.

Neonates and Infants

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.

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.

No interaction studies have been performed. Possible interaction may occur with hydroxocobalamin.

Sodium nitrite should be used with caution in the presence of other drugs that may cause methemoglobinemia such as procaine and nitroprusside. It should also be used with caution in the presence of other drugs that can reduce blood pressure.

Pregnancy

Based on human experience sodium nitrite is suspected to cause congenital malformations when administered during pregnancy. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

Sodium nitrite should not be used during pregnancy unless the clinical condition of the woman requires treatment with sodium nitrite.

Breastfeeding

It is unknown whether sodium nitrite is excreted in human milk. A risk to the suckling child cannot be excluded.

Breast-feeding should be discontinued during treatment with sodium nitrite.

Fertility

There are no fertility data from the use of sodium nitrite in animals.

Not relevant.

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.

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, fatigue, weakness, generalized numbness and tingling

^*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.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system: Yellow Card Scheme – Website: www.mhra.gov.uk/yellowcard.

Chemical incompatibility has been reported between sodium nitrite and hydroxocobalamin and these drugs should not be administered simultaneously through the same IV line. No chemical incompatibility has been reported between sodium thiosulfate and sodium nitrite, when administered sequentially through the same IV line.