Version April 2023
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, use sodium nitrite to treat acute life-threatening cyanide poisoning and use it with caution in patients in whom the diagnosis of cyanide poisoning is uncertain.
Closely monitor patients to ensure adequate perfusion and oxygenation during treatment with sodium nitrite.
Consider alternative therapeutic approaches in patients known to have diminished oxygen or cardiovascular reserve (eg, smoke inhalation victims, preexisting anemia, cardiac or respiratory compromise) and those at higher risk of developing methemoglobinemia (eg, congenital methemoglobin reductase deficiency) because they are at greater risk of potentially life-threatening adverse events related to the use of sodium nitrite.
Note: Consultation with a clinical toxicologist or poison control center is highly recommended.
Cyanide poisoning: IV: Note: Given in conjunction with sodium thiosulfate. Administer sodium nitrite first, followed immediately by the administration of sodium thiosulfate: 300 mg (10 mL of a 3% solution); may repeat at one-half the original dose if symptoms of cyanide toxicity return. Sodium nitrite is generally discontinued for methemoglobin levels >30%.
Alternatively, in patients who are unable to tolerate significant methemoglobinemia (eg, patients with comorbidities that compromise oxygen delivery, such as heart disease, lung disease), dosing may be based on hemoglobin levels (when rapid bedside testing is available) to prevent fatal methemoglobinemia; see table (Berlin, 1970):
|
Hemoglobin Level (g/dL) |
Dose of 3% Sodium Nitrite Solution (maximum dose: 10 mL) |
|---|---|
|
7 |
0.19 mL/kg |
|
8 |
0.22 mL/kg |
|
9 |
0.25 mL/kg |
|
10 |
0.27 mL/kg |
|
11 |
0.3 mL/kg |
|
12 |
0.33 mL/kg |
|
13 |
0.36 mL/kg |
|
14 |
0.39 mL/kg |
Note: Monitor the patient for 24 to 48 hours; if symptoms return, repeat sodium nitrite and sodium thiosulfate at one-half the original dose.
Hydrogen sulfide poisoning (off-label use): Note: May be beneficial if given immediately (within minutes) following exposure to hydrogen sulfide (ATSDR 2014; Guidotti 2010; Policastro 2007; Yalamanchili 2008; expert opinion); use has not been validated in clinical trials (Holstege 2019). Do not administer sodium thiosulfate (ATSDR 2014).
IV: 300 mg (10 mL of a 3% solution) (ATSDR 2014; Policastro 2007).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment provided in the manufacturer’s labeling; however, renal elimination of sodium nitrite is significant and risk of adverse effects may be increased in patients with renal impairment.
No dosage adjustment provided in manufacturer’s labeling (has not been studied).
Cyanide poisoning: IV: 6 mg/kg (0.2 mL/kg or 6-8 mL/m2 of a 3% solution); maximum dose: 300 mg (10 mL of a 3% solution); may repeat at one-half the original dose if symptoms of cyanide toxicity return. Note: Given in conjunction with sodium thiosulfate. Administer sodium nitrite first, followed immediately by the administration of sodium thiosulfate. Sodium nitrite is generally discontinued for methemoglobin levels >30%.
Alternatively, in patients who are unable to tolerate significant methemoglobinemia (eg, patients with comorbidities that compromise oxygen delivery, such as heart disease, lung disease): Refer to adult dosing.
Note: Monitor the patient for 24-48 hours; if symptoms return, repeat sodium nitrite and sodium thiosulfate at one-half the original dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling; however, renal elimination of sodium nitrite is significant and risk of adverse effects may be increased in patients with renal impairment.
There are no dosage adjustments provided in manufacturer’s labeling (has not been studied).
Refer to adult dosing. Use caution due to the likelihood of decreased renal function.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 30 mg/mL (10 mL)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 30 mg/mL (10 mL)
IV: Administer via slow IV injection (2.5 to 5 mL/minute) as soon as possible after diagnosis of acute, life-threatening cyanide poisoning; follow immediately with the administration of sodium thiosulfate for cyanide-poisoned patients (do not administer sodium thiosulfate in hydrogen sulfide-poisoned patients [ATSDR 2014]). Some recommend slower administration of sodium nitrite (≥5 minutes [ATSDR 2014]). Decrease the rate of infusion in the event of significant hypotension.
IV: Administer by slow IV injection at a rate of 2.5 to 5 mL/minute as soon as possible after diagnosis of acute, life-threatening cyanide poisoning; follow immediately with the administration of sodium thiosulfate. Decrease the rate of infusion in the event of significant hypotension.
Cyanide poisoning: Treatment of acute, life-threatening cyanide poisoning.
Note: The preferred antidote for the treatment of acute cyanide poisoning is hydroxocobalamin, especially in patients who have concurrent carbon monoxide poisoning (eg, smoke inhalation), significant anemia, or G6PD deficiency (Anseeuw 2013). Sodium nitrite in combination with sodium thiosulfate should be considered only if hydroxocobalamin is unavailable, there is a contraindication to the use of hydroxocobalamin, or if the patient has a known sensitivity to hydroxocobalamin or vitamin B12 analogues. Consider consultation with a poison control center or clinical toxicologist.
Hydrogen sulfide poisoning
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined.
Cardiovascular: Cardiac arrhythmia, flushing, hypotension, palpitations, syncope, tachycardia
Central nervous system: Anxiety, coma, confusion, dizziness, fatigue, headache, numbness, paresthesia, seizure, tingling sensation (at injection site)
Dermatologic: Diaphoresis, urticaria
Endocrine & metabolic: Acidosis
Gastrointestinal: Abdominal pain, nausea, vomiting
Hematologic & oncologic: Methemoglobinemia
Neuromuscular & skeletal: Weakness
Ophthalmic: Blurred vision
Respiratory: Cyanosis, dyspnea, tachypnea
There are no contraindications listed within the manufacturer's labeling.
Concerns related to adverse effects:
• Hypotension: [US Boxed Warning]: Sodium nitrite may cause severe hypotension resulting in diminished oxygen-carrying capacity; serious adverse effects may occur at doses less than twice the recommended therapeutic dose. Monitor for adequate perfusion and oxygenation; ensure patient is euvolemic. Use with caution in patients where the diagnosis of cyanide poisoning is uncertain, patients with pre-existing diminished oxygen or cardiovascular reserve (eg, smoke inhalation victims, anemia, substantial blood loss, and cardiac or respiratory compromise), and in patients who may be susceptible to injury from vasodilation; the use of hydroxocobalamin is recommended in these patients.
• Methemoglobinemia: [US Boxed Warning]: Sodium nitrite may cause methemoglobin formation resulting in diminished oxygen-carrying capacity; serious adverse effects may occur at doses less than twice the recommended therapeutic dose. Monitor for adequate perfusion and oxygenation. Use with caution in patients where the diagnosis of cyanide poisoning is uncertain, patients with pre-existing diminished oxygen or cardiovascular reserve (eg, smoke inhalation victims, anemia, substantial blood loss, and cardiac or respiratory compromise), and in patients at greater risk for developing methemoglobinemia (eg, congenital methemoglobin reductase deficiency); the use of hydroxocobalamin is recommended in these patients. Use with caution with concomitant medications known to cause methemoglobinemia (eg, nitroglycerin, phenazopyridine). Sodium nitrite is generally discontinued for methemoglobin levels >30%. Intravenous methylene blue and exchange transfusion have been used to treat life-threatening methemoglobinemia.
Disease-related concerns:
• Anemia: Use with caution; patients with anemia will form more methemoglobin. Dosage reduction in proportion to oxygen-carrying capacity is recommended.
• Glucose-6-phosphate dehydrogenase deficiency: Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at an increased risk for hemolytic crisis following sodium nitrite administration; consider alternative treatment options if possible. Monitor for an acute drop in hematocrit; exchange transfusion may be necessary.
• Renal impairment: Use with caution; sodium nitrite undergoes substantial renal excretion. Risk for adverse events may be increased.
Special populations:
• Older adult: Use with caution due to the likelihood of decreased renal function.
• Fire victims: Fire victims may present with both cyanide and carbon monoxide poisoning. In this scenario, hydroxocobalamin is the agent of choice for cyanide intoxication since the induction of methemoglobinemia (due to sodium nitrite) is contraindicated until carbon monoxide levels return to normal due to the risk of severe tissue hypoxia. Methemoglobinemia decreases the oxygen-carrying capacity of hemoglobin and the presence of carbon monoxide prevents hemoglobin from releasing oxygen to the tissues. In these patients, sodium thiosulfate may be used alone to promote the clearance of cyanide; however, hydroxocobalamin is still the preferred cyanide antidote because sodium thiosulfate has a slow onset of action.
• Pediatric: Methemoglobin reductase, which is responsible for converting methemoglobin back to hemoglobin, has reduced activity in pediatric patients. In addition, infants and young children have some proportion of fetal hemoglobin which forms methemoglobin more readily than adult hemoglobin. Therefore, pediatric patients (eg, neonates and infants <6 months of age) are more susceptible to excessive nitrite-induced methemoglobinemia. Hydroxocobalamin will circumvent this problem and may be a more effective and rapid alternative.
Other warnings/precautions:
• Appropriate use: Cyanide poisoning: Due to the risk for serious adverse effects, use with caution in patients where the diagnosis of cyanide poisoning is uncertain. However, if clinical suspicion of cyanide poisoning is high, treatment should not be delayed. Signs of cyanide poisoning may include altered mental status, cardiovascular collapse, chest tightness, mydriasis, nausea/vomiting, dyspnea, hyper-/hypotension, plasma lactate ≥8 mmol/L. Treatment of cyanide poisoning should include external decontamination and supportive therapy. Consider consultation with a poison control center at 1-800-222-1222.
• Initiation of treatment: Collection of pretreatment blood cyanide concentrations does not preclude administration and should not delay administration in the emergency management of highly suspected or confirmed cyanide toxicity. Pretreatment levels may be useful as postinfusion levels may be inaccurate.
• Return of symptoms: Patients receiving treatment for acute cyanide poisoning must be monitored for return of symptoms for 24-48 hours; repeat treatment (one-half the original dose) should be administered if symptoms return.
• Smoke inhalation: Use nitrites cautiously in patients with cyanide poisoning related to smoke inhalation because methemoglobinemia and carboxyhemoglobinemia may worsen oxygen-carrying capacity.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Risk X: Avoid combination
Dapsone (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy
Local Anesthetics: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Methemoglobinemia Associated Agents: May enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitric Oxide: May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Teratogenic effects have been observed following maternal exposure to high concentrations of sodium nitrite in drinking water.
Sodium nitrite causes methemoglobin formation, resulting in diminished oxygen-carrying capacity; fetal hemoglobin may be more susceptible to excessive nitrite-induced methemoglobinemia.
In general, medications used as antidotes should take into consideration the health and prognosis of the mother; antidotes should be administered to pregnant women if there is a clear indication for use and should not be withheld because of fears of teratogenicity (Bailey 2003). However, sodium nitrite is not the preferred treatment of cyanide toxicity,(Anseeuw 2013) and other treatments may be preferred for pregnant women (Culnan 2018).
It is not known if sodium nitrite is present in breast milk.
When cyanide poisoning is the indication for use of amyl nitrite, clinicians should be aware that the breastfed infant may have been exposed to cyanide and may also require treatment for cyanide poisoning (De Capitani 2017); consultation with a clinical toxicologist or poison control center is highly recommended.
The manufacturer recommends that caution be exercised when administering sodium nitrite to breastfeeding women. Breastfeeding is not a contraindication to use.
Monitor for at least 24 to 48 hours after administration; blood pressure and heart rate during and after infusion; hemoglobin/hematocrit; co-oximetry; serum lactate levels; venous-arterial PO2 gradient; serum methemoglobin and oxyhemoglobin. Pretreatment cyanide levels may be useful diagnostically, but if the patient is acutely ill, do not delay sodium nitrite therapy while awaiting laboratory results.
Sodium nitrite promotes the formation of methemoglobin which competes with cytochrome oxidase for the cyanide ion as well as hydrogen sulfide (Holstege 2019). Cyanide combines with methemoglobin to form cyanomethemoglobin, thereby freeing the cytochrome oxidase and allowing aerobic metabolism to continue. Formation of nitric oxide may also displace cyanide from cytochrome c oxidase (Howland 2019).
Onset: Peak effect: Methemoglobinemia: 30 to 60 minutes
Duration of action: Methemoglobinemia: ~55 minutes
Metabolism: To ammonia and other metabolites
Excretion: Urine (~40% as unchanged drug)
Solution (Sodium Nitrite Intravenous)
30 mg/mL (per mL): $10.70
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