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Pralidoxime

Medically reviewed on September 10, 2018

Pronunciation

(pra li DOKS eem)

Index Terms

  • 2-PAM
  • 2-Pyridine Aldoxime Methochloride
  • 2PAM
  • Pralidoxime Chloride

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Auto-injector, Intramuscular, as chloride:

Generic: 600 mg/2 mL (2 mL)

Solution Reconstituted, Intravenous, as chloride:

Protopam Chloride: 1 g (1 ea)

Brand Names: U.S.

  • Protopam Chloride

Pharmacologic Category

  • Antidote

Pharmacology

Reactivates cholinesterase that had been inactivated by phosphorylation due to exposure to organophosphate pesticides and cholinesterase-inhibiting nerve agents (eg, terrorism and chemical warfare agents such as sarin) by displacing the enzyme from its receptor sites; removes the phosphoryl group from the active site of the inactivated enzyme

Distribution

Vdss: 0.6 to 2.7 L/kg; Severely poisoned pediatric patients (n=11; age: 0.8 to 18 years): ~9 L/kg (range: 1.7 to 13.8 L/kg) (Schexnayder 1998); may increase with increasing severity of organophosphate intoxication

Metabolism

Hepatic

Excretion

Urine (80% as metabolites and unchanged drug)

Time to Peak

Serum: IV: 5 to 15 minutes; IM: ~35 minutes

Half-Life Elimination

Apparent: 74 to 77 minutes; Poisoned patients (IM, IV): 3 to 4 hours; Pediatric patients (n=11; age: 0.8 to 18 years): 2.4 to 5 hours

Protein Binding

None

Special Populations: Renal Function Impairment

Decreased renal function will result in increased blood levels of pralidoxime.

Use: Labeled Indications

Treatment of muscle weakness and/or respiratory depression secondary to poisoning due to organophosphate anticholinesterase pesticides and terrorism nerve agents; control of overdose of anticholinesterase medications used to treat myasthenia gravis (ambenonium, neostigmine, pyridostigmine)

Limitations of use: Pralidoxime is not indicated for the treatment of carbamate poisoning (WHO 2006); acetylcholinesterase is weakly, but not permanently, affected by carbamates.

Contraindications

There are no absolute contraindications listed within the manufacturer’s labeling. Note: According to the manufacturer, relative contraindications include hypersensitivity to pralidoxime or any component of the formulation and other situations where the risk of administration clearly outweighs possible benefit.

Dosing: Adult

Organophosphate poisoning (eg, pesticides and nerve agents): Note: Must be used in conjunction with atropine; a response to atropine should be established before pralidoxime is administered. A combination product containing both pralidoxime and atropine is available as an auto-injector kit (eg, Duodote) which is used most often by civilian first responders or by military personnel for self-injected or buddy administration. The response to pralidoxime is highly variable and is dependent on the organophosphate, the length of time since the exposure, body mass and the toxic dose (Lee 2014; Moon 2015); the optimal dosing regimen for pralidoxime has not been established (WHO 2006). IM or SubQ administration should be considered when IV administration is not feasible:

IV: Note: In patients with severe intoxication, maintenance treatment should be administered as a continuous infusion when possible (WHO 2006).

Loading dose: 30 mg/kg (maximum: 2,000 mg) (Howland 2015; Roberts 2007) or 2,000 mg (WHO 2006)

Maintenance: 8 to 10 mg/kg/hour (maximum: 650 mg/hour) (Howland 2015; Roberts 2007) or 500 mg/hour (WHO 2006); severe intoxication may result in prolonged redistribution of the organophosphate; the duration of therapy should reflect the clinical status of the patient

Manufacturer labeling:

Loading dose: 1,000 to 2,000 mg

Maintenance: Repeat bolus of 1,000 to 2,000 mg after 1 hour if muscle weakness has not been relieved; repeat every 10 to 12 hours thereafter, as needed. When using intermittent infusion dosing, the World Health Organization (WHO) recommends repeated dosing every 4 to 6 hours as needed (WHO 2006).

IM:

Mild symptoms: 600 mg; repeat as needed for persistent mild symptoms every 15 minutes to a maximum total dose of 1,800 mg; may administer doses in rapid succession if severe symptoms develop

Severe symptoms: 600 mg; repeat twice in rapid succession to deliver a total dose of 1,800 mg

Persistent symptoms: May repeat the entire series (1,800 mg) beginning ~1 hour after administration of the last injection

Anticholinesterase overdose (eg, neostigmine, pyridostigmine): IV: 1,000 to 2,000 mg; followed by increments of 250 mg every 5 minutes as needed

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Organophosphate poisoning (eg, pesticides and nerve agents): Note: Must be used in conjunction with atropine; a response to atropine should be established before pralidoxime is administered. A combination product containing both pralidoxime and atropine is available as an auto-injector kit (eg, Duodote) which is used most often by civilian first-responders or by military personnel for self-injected or buddy-administration. The response to pralidoxime is highly variable and is dependent on the organophosphate, the length of time since the exposure, body mass, and the toxic dose (Lee 2014; Moon 2015); the optimal dosing regimen for pralidoxime has not been established (WHO 2006). IM or SubQ administration should be considered when IV administration is not feasible:

IV: Note: In patients with severe intoxication, maintenance treatment should be administered as a continuous infusion when possible (WHO 2006).

Children and Adolescents ≤16 years:

Loading dose: 20 to 50 mg/kg (maximum: 2,000 mg/dose)

Maintenance: 10 to 20 mg/kg/hour. Alternatively, a repeat bolus of 20 to 50 mg/kg (maximum: 2,000 mg/dose) may be administered after 1 hour if muscle weakness has not been relieved and repeated every 10 to 12 hours thereafter, as needed. When using intermittent infusion dosing, the World Health Organization (WHO) recommends repeated dosing every 4 to 6 hours as needed (WHO 2006). Severe intoxication may result in prolonged redistribution of the organophosphate; the duration of therapy should reflect the clinical status of the patient.

Adolescents >16 years: Refer to adult dosing.

IM:

Children <40 kg:

Mild symptoms: 15 mg/kg; repeat as needed for persistent mild symptoms every 15 minutes to a maximum total dose of 45 mg/kg; may administer doses in rapid succession if severe symptoms develop

Severe symptoms: 15 mg/kg; repeat twice in rapid succession to deliver a total dose of 45 mg/kg

Persistent symptoms: May repeat the entire series (45 mg/kg) beginning ~1 hour after administration of the last injection

Children ≥40 kg and Adolescents: Refer to adult dosing.

Dosing: Renal Impairment

No specific dosage adjustment provided in manufacturer's labeling; however, because pralidoxime is excreted in the urine, dosage reduction is recommended in patients with renal impairment.

Dosing: Hepatic Impairment

No dosage adjustment provided in the manufacturer’s labeling; undergoes hepatic metabolism.

Reconstitution

Powder for solution:

IV administration: Dilute 1,000 mg with 20 mL SWFI to make a concentration of 50 mg/mL; this concentration may be administered in fluid-restricted patients or in situations where a more rapid administration is required. For administration in all other patients, the reconstituted solution should be further diluted with NS to a final concentration of 10 to 20 mg/mL. Discard any unused portion of vial.

IM administration: Dilute 1,000 mg with 3.3 mL SWFI to a final concentration of ~300 mg/mL; discard any unused portion of vial.

Administration

IV:

Loading dose: Infuse as a 10 to 20 mg/mL solution over 15 to 30 minutes. Alternatively, if this is not practical or if pulmonary edema is present and/or fluid restriction is necessary, may administer as a 50 mg/mL solution by slow IV injection over ≥5 minutes.

Maintenance dose: Administer as a continuous or intermittent infusion at a rate not to exceed 200 mg/minute.

IM, SubQ: May administer IM (preferred) or SubQ if IV administration is not feasible. For pediatric patients, IM injection should be into the anterolateral aspect of the thigh. If using the auto-injector (solution for IM injection), remove gray safety cap and place black end against outer thigh. Push hard until injector administers, hold in place for 10 seconds, then remove and massage area of injection. Auto-injector is intended for use by military personnel for self or buddy administration; may also be administered by qualified civilian emergency responders who have received adequate training on the recognition and treatment of nerve agent intoxication.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Drug Interactions

There are no known significant interactions.

Adverse Reactions

Frequency not defined.

Cardiovascular: Cardiac arrest, hypertension, tachycardia

Central nervous system: Dizziness, drowsiness, headache, paralysis, seizure

Dermatologic: Maculopapular rash

Gastrointestinal: Nausea, vomiting

Hepatic: Increased serum ALT (transient), increased serum AST (transient)

Local: Pain at injection site (IM)

Neuromuscular & skeletal: Fasciculations, increased creatine phosphokinase, laryngospasm, muscle rigidity, weakness

Ophthalmic: Abnormal accommodation, blurred vision, diplopia

Renal: Renal insufficiency

Respiratory: Apnea, hyperventilation

Warnings/Precautions

Disease-related concerns:

• Carbamate poisoning: Pralidoxime is not indicated for the treatment of carbamate poisoning (WHO 2006); acetylcholinesterase is weakly, but not permanently, affected by carbamates.

• Myasthenia gravis: Use with caution in patients with myasthenia gravis; administration may precipitate a myasthenic crisis.

• Nonanticholinesterase poisoning: Pralidoxime is not indicated for the treatment of poisoning due to phosphorus, inorganic phosphates, or organophosphates without anticholinesterase activity.

• Renal impairment: Use with caution in patients with renal impairment; dosage modification required.

Other warnings/precautions:

• Appropriate use: Clinical symptoms that are consistent with suspected organophosphate poisoning (eg, organophosphate anticholinesterase pesticides and nerve agents) should be treated with the antidote immediately; administration should not be delayed for confirmatory laboratory tests. Treatment should include proper evacuation and decontamination procedures as indicated; medical personnel should protect themselves from inadvertent contamination. Antidote administration is intended only for initial management; definitive and more intensive medical care is required following administration. Individuals should not rely solely on antidote for treatment; the concomitant use of atropine will be necessary and other supportive measures (eg, artificial respiration) may still be required.

Monitoring Parameters

Heart rate, respiratory rate, muscle fasciculations and strength, pulse oximetry; cardiac monitor and blood pressure monitor required for IV administration

Pregnancy Risk Factor

C

Pregnancy Considerations

Animal reproduction studies have not been conducted. A case report did not show evidence of adverse events after pralidoxime administration during the second trimester (Kamha 2005). 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).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience fatigue, nausea, blurred vision, or injection site pain. Have patient report immediately to prescriber difficulty breathing, severe dizziness, angina, severe headache, vision changes, muscle weakness, or tachycardia (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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