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Sodium Nitrite (Systemic)


VA CLASSIFICATION
Primary: AD200



Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antidote (to cyanide poisoning)—

Indications

Accepted

Toxicity, cyanide (treatment adjunct)—Sodium nitrite, in conjunction with sodium thiosulfate, is indicated for use as an antidote in the treatment of cyanide poisoning. {01} {02} {03} {04} {07} {08}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    69 {09}


pH
    Between 7 and 9. {10}

Mechanism of action/Effect:

Antidote (to cyanide poisoning)—Sodium nitrite promotes formation of methemoglobin, which combines with cyanide to form nontoxic cyanmethemoglobin. {01} {04} {05} {06}


Other actions/effects:

Sodium nitrite produces vasodilation by relaxing vascular smooth muscle. {02} {04} {08} {13}

Time to peak effect:

30 to 70 minutes after injection. {05} {06}


Precautions to Consider

Pregnancy/Reproduction

Problems in humans have not been documented.

Breast-feeding

It is not known whether sodium nitrite is distributed into breast milk.

Pediatrics

Appropriate studies performed to date have not demonstrated pediatrics-specific problems that would limit the usefulness of sodium nitrite in children.


Geriatrics


Appropriate studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of sodium nitrite in the elderly.

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
» Methemoglobinemia, acquired or congenital{14}{15}    (may be exacerbated)


Sensitivity to sodium nitrite

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Arterial blood gas determinations{14}    (recommended frequently during administration of 100% oxygen and when attempting to correct severe metabolic acidosis)


Blood pressure determinations{02}{04}{06}    (recommended to guide the rate of administration of sodium nitrite; rapid administration may result in excessive vasodilation and hypotension)


» Methemoglobin concentrations{02}{04}{11}    (recommended periodically during administration to ensure that the methemoglobin concentration does not exceed 40% in adults or 30% in children)




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Hypotension
    
vasodilation, excessive —caused by rapid administration{02}{04}{06}{07}{08}{11}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Nausea or vomiting {01}{04}{08}





Overdose
For specific information on the agents used in the management of sodium nitrite overdose, see Methylene Blue (Systemic) monograph.

For more information on the management of overdose, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive (in order of occurrence):
    
Cyanosis (bluish fingernails, lips, or skin){01}{02}{03}{08}{13}
    
headache {04}{08}{13}
    
unusual tiredness or weakness {13}
    
tachycardia {04}{13}
    
shortness of breath {04}
    
dizziness, extreme, or fainting {04}{08}{13}
    
coma {01}{04}{13}

Note: Cyanosis may occur at blood methemoglobin concentrations of 15%; however, symptoms usually do not appear until concentrations reach 30 to 40%. {08} {13}



Treatment of overdose
Specific treatment—Intravenous administration of methylene blue in a dose of 1 to 2 mg per kg of body weight (mg/kg) given over five to ten minutes. {01} {04} {08} {13} The dose may be repeated after one hour if necessary, {01} {08} {13} but the total dose should not exceed 7 mg/kg. {08} {13} Extreme caution should be exercised when administering methylene blue to patients likely to have substantial amounts of cyanide bound to methemoglobin because methylene blue increases cyanide release. {07} {08}

Supportive care—Oxygen inhalation and transfusion of fresh whole blood should be considered. {01} {08} {11}


General Dosing Information
Cyanide poisoning is rapidly fatal. Inhalation of cyanide gas produces symptoms of cyanide toxicity within seconds, followed by death within minutes. Oral ingestion of cyanide produces symptoms of toxicity within minutes, followed by death within minutes or hours. {08} Blood cyanide concentrations often are not available for several hours. {02} {08} Therefore, therapy should be instituted immediately based upon reasonable suspicion of cyanide toxicity. {01} {07} {08}

Supportive therapy includes moving the patient to an uncontaminated area {01} and/or removing contaminated clothing; {01} {08} administering 100% oxygen; {01} {02} {08} {11} controlling seizures with anticonvulsants; {02} correcting metabolic acidosis with bicarbonate; {02} {08} and supporting pulse and blood pressure with fluids, atropine, or vasopressors. These measures alone may allow survival in relatively mild cases of cyanide toxicity. {02}

In more severe cases of cyanide toxicity, chances of survival are increased by specific antidote administration. {02} Antidotal therapy should be started by breaking an amyl nitrite inhalant, holding it in front of the patient's mouth, and allowing the patient to inhale for 15 seconds. The inhalant should then be taken away for 15 seconds. This procedure may be repeated until an intravenous line is established and sodium nitrite is prepared. {01} {08} {11} Amyl nitrite should not be administered if an intravenous line already has been established and the sodium nitrite is readily available. {07} {08} Amyl nitrite, if given, should then be discontinued and sodium nitrite administered. Immediately following the injection of sodium nitrite, sodium thiosulfate should be administered intravenously in a dose of 12.5 grams (50 mL of a 25% solution) (for adults) {01} {02} {03} {04} {07} {08} {11} and 412.5 mg per kg of body weight {08} {11} or 7 grams per square meter of body surface area (for children), {01} at a rate of 0.625 to 1.25 grams (2.5 to 5 mL) per minute. {08} {11}

If signs of cyanide toxicity are still present 2 hours following administration of sodium nitrite and sodium thiosulfate, administration of both may be repeated at one-half the original dose. {01} {04} {07}

If cyanide was ingested, gastric lavage should follow antidotal therapy. {12}


Parenteral Dosage Forms

SODIUM NITRITE INJECTION USP

Usual adult and adolescent dose
Cyanide toxicity
Intravenous, 300 mg (10 mL of a 3% solution) {01} {02} {04} {08} {11} administered at a rate of 75 to 150 mg (2.5 to 5 mL) per minute. {01} {04} {07} {08} {11}


Usual pediatric dose
Cyanide toxicity
Intravenous, 6 mg (0.2 mL) per kg of body weight or approximately 180 to 240 mg (6 to 8 mL) per square meter of body surface area {01} {07} administered at a rate of 75 to 150 mg (2.5 to 5 mL) per minute. {01} {04} {07} {08} {11}


Usual pediatric prescribing limits
300 mg (10 mL). {01} {08}

Strength(s) usually available
U.S.—


300 mg per 10 mL (Rx)[Generic]

Canada—


300 mg per 10 mL (Rx)[Generic]

Note: Sodium nitrite is a component of the Cyanide Antidote Package. Also contained in the kit are: amyl nitrite inhalants (0.3 mL) and sodium thiosulfate injection (12.5 grams per 50 mL). {01}


Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Stability:
The components of the Cyanide Antidote Package contain preservatives, which allow the unopened solutions to remain stable for several years. {01} However, the expiration date of the kit should be observed. {11}



Revised: 03/24/1994



References
  1. Cyanide Antidote Package package insert (Lilly—US and Canada), Rev 8/30/90, Rec 3/8/93.
  1. Hall AH, Rumack BH. Clinical toxicology of cyanide. Ann Emerg Med 1986; 15: 1067-74.
  1. Marrs TC. Antidotal treatment of acute cyanide poisoning. Adverse Drug React Acute Poisoning Rev 1988; 4: 179-206.
  1. Baskin SI, Horowitz AM, Nealley EW. The antidotal action of sodium nitrite and sodium thiosulfate against cyanide poisoning. J Clin Pharmacol 1992; 32: 368-75.
  1. Scolnick B, Hamel D, Woolf AD. Successful treatment of life-threatening proprionitrile exposure with sodium nitrite/sodium thiosulfate followed by hyperbaric oxygen. J Occup Med 1993; 35: 577-80.
  1. Kirk MA, Gerace R, Kulig KW. Cyanide and methemoglobin kinetics in smoke inhalation victims treated with the cyanide antidote kit. Ann Emerg Med 1993; 22: 1413-8.
  1. Nipride package insert (Roche—US), Rev 10/90, Rec 12/12/90.
  1. Ellenhorn MJ, Barceloux DG, editors. Medical toxicology diagnosis and treatment of human poisoning. New York: Elsevier, 1988: 829-35, 844-52.
  1. Fleeger CA, editor. USAN 1994. USAN and the USP dictionary of drug names. Rockville, MD: The United States Pharmacopeial Convention, Inc., 1993: 609.
  1. The United States pharmacopeia. The national formulary. USP 22nd revision (January 1, 1990). NF 17th ed (January 1, 1990). Rockville, MD: The United States Pharmacopeial Convention, Inc., 1990: 1264.
  1. Drug evaluations subscription. Chicago: American Medical Association, Spring 1990: 4:14-4:15.
  1. Gilman AG, Rall TW, Nies AS, Taylor P, editors. Goodman and Gilman's the pharmacological basis of therapeutics. 8th ed. New York: Pergamon Press, 1990: 1630-1.
  1. Curry S. Methemoglobinemia. Ann Emerg Med 1982; 11: 214-21.
  1. Panel comment, 1/94.
  1. Panel comment, 12/93.
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