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Pralidoxime: Drug information

Pralidoxime: Drug information
(For additional information see "Pralidoxime: Patient drug information" and see "Pralidoxime: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Protopam Chloride
Pharmacologic Category
  • Antidote
Dosing: Adult
Anticholinesterase overdose

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

Organophosphate poisoning

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, 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 2018; Roberts 2007) or 2,000 mg (WHO 2006).

Maintenance:

Continuous infusion (preferred): 8 to 10 mg/kg/hour (maximum: 650 mg/hour) (Howland 2018; 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.

Intermittent infusion: May repeat loading dose after 1 to 2 hours if muscle weakness has not been relieved, followed by repeated dosing every 4 to 6 hours as needed (WHO 2006).

IM (preferred), SUBQ:

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.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; however, because pralidoxime is excreted in the urine, dosage reduction is recommended in patients with renal impairment.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; undergoes hepatic metabolism.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Pralidoxime: Pediatric drug information")

Anticholinesterase overdose

Anticholinesterase overdose (eg, neostigmine, pyridostigmine): Very limited data available: Children and Adolescents: IV: 30 mg/kg/dose for 2 doses; dosing based on a case report describing rivastigmine poisoning in a 3-year-old who received atropine and 2 doses of pralidoxime (administered at 5 hours and 6 hours postingestion); after second dose, clinical symptoms improved and an increase in plasma acetylcholinesterase activity was observed (Saz 2018).

Organophosphate poisoning

Organophosphate poisoning (eg, pesticides, 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 autoinjector kit (eg, DuoDote) for use in patients weighing >41 kg. The response to pralidoxime is highly variable and is dependent on the organophosphate (some warfare and terrorism agents bind irreversibly within minutes), the length of time since the exposure, body mass index, and the toxic dose (Lee 2014; Moon 2015); the optimal dosing regimen for pralidoxime has not been established (WHO 2006). Administration via IM or SUBQ routes should be considered when IV administration is not feasible.

IV:

Infants, Children, and Adolescents ≤16 years:

Loading dose: IV: 20 to 50 mg/kg; maximum dose: 2,000 mg/dose (AAP [Shenoi 2020]; manufacturer's labeling).

Maintenance dosing: Note: In patients with severe intoxication, maintenance treatment should be administered as a continuous infusion when possible (WHO 2006). The duration of therapy based on clinical status of the patient; severe intoxication may result in prolonged redistribution of the organophosphate.

Continuous IV Infusion: 10 to 20 mg/kg/hour not to exceed 500 mg/hour (AAP [Shenoi 2020]; manufacturer's labeling).

Intermittent IV: 20 to 50 mg/kg; maximum dose: 2,000 mg/dose; may be repeated after 1 hour if muscle weakness has not been relieved; then may repeat every 10 to 12 hours as needed (per the manufacturer); however, more frequent dosing of 4 to 6 hours as needed has been recommended (WHO 2006).

Adolescents >16 years:

Loading dose:

Weight-directed dosing: IV: 30 mg/kg; maximum dose: 2,000 mg/dose (Howland 2018; Roberts 2007).

Fixed dosing: IV: 2,000 mg (WHO 2006). Note: A lower fixed dose of 1,000 mg is recommended by the manufacturer; however, this regimen may result in sub-therapeutic concentrations (WHO 2006).

Maintenance dose: Note: In patients with severe intoxication, maintenance treatment should be administered as a continuous infusion when possible (WHO 2006).The duration of therapy based on clinical status of the patient; severe intoxication may result in prolonged redistribution of the organophosphate.

Continuous IV Infusion:

Weight-directed dosing: 8 to 10 mg/kg/hour, not to exceed a maximum of 650 mg/hour as a continuous IV infusion (Howland 2018; Roberts 2007).

Fixed dosing: 500 mg/hour (WHO 2006).

Intermittent IV: 1,000 to 2,000 mg administered 1 hour after loading dose if muscle weakness has not been relieved; repeat every 10 to 12 hours as needed (per the manufacturer); however, more frequent dosing of 4 to 6 hours as needed has been recommended (WHO 2006).

IM, SUBQ: Note: If IV administration not feasible, the IM route is preferred over subcutaneous.

Infants, Children, and Adolescents <40 kg:

Mild symptoms: IM, SUBQ: 15 mg/kg/dose; 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: IM, SUBQ: 15 mg/kg/dose; repeat twice in rapid succession to deliver a total dose of 45 mg/kg (total).

Persistent symptoms: IM, SUBQ: If symptoms persist after a complete 3-dose course, may repeat the entire series (45 mg/kg in 3 divided doses) beginning ~1 hour after administration of the last injection.

Children and Adolescents ≥40 kg:

Mild symptoms: IM, SUBQ: 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: IM, SUBQ: 600 mg; repeat twice in rapid succession to deliver a total dose of 1,800 mg (total).

Persistent symptoms: IM, SUBQ: If symptoms persist after a complete 3-dose course, may repeat the entire series (1,800 mg in 3 divided doses) beginning ~1 hour after administration of the last injection.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; however, because pralidoxime is excreted in the urine, dosage reduction is recommended in patients with renal impairment.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. 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

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.

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.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution Auto-injector, Intramuscular, as chloride:

Generic: 600 mg/2 mL (2 mL [DSC])

Solution Reconstituted, Intravenous, as chloride:

Protopam Chloride: 1 g (1 ea)

Generic Equivalent Available: US

May be product dependent

Pricing: US

Solution (reconstituted) (Protopam Chloride Intravenous)

1 g (per each): $104.04

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Administration: Adult

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. If using the auto-injector (solution for IM injection) for IM administration, 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.

Administration: Pediatric

Parenteral:

IM: Use a 300 mg/mL solution; either autoinjector or reconstituted powder for injection may be used; in infants and children, administer intramuscularly in the anterolateral aspect of the thigh.

IV: Note: Rapid IV infusion may be associated with temporary worsening of cholinergic manifestations (eg, tachycardia, laryngospasm, muscle rigidity, cardiac arrest) in adults; in children, muscle fasciculations, apnea, and convulsions have also been reported.

Loading dose: Infuse over 15 to 30 minutes; if maximally concentrated solution (50 mg/mL) may be administered over ≥5 minutes not to exceed 200 mg/minute. Some experts recommend slower administration over 30 to 60 minutes (AAP [Shenoi 2020]).

Maintenance dose (intermittent infusion): Infuse over 15 to 30 minutes a rate not to exceed 200 mg/minute.

SUBQ: May administer SUBQ if IM or IV administration is not feasible.

Use: Labeled Indications

Anticholinesterase overdose: Treatment of overdose of anticholinesterase medications used to treat myasthenia gravis (ambenonium, neostigmine, pyridostigmine).

Organophosphate poisoning (eg, pesticides, nerve agents): Treatment of muscle weakness and/or respiratory depression secondary to poisoning due to organophosphate anticholinesterase pesticides and terrorism nerve agents.

Note: Used in conjunction with atropine (Howland 2018); the role of oximes in organophosphate poisoning remains unclear and efficacy is dependent on the organophosphate ingested, the length of time since the exposure, and the toxic dose (Eddleston 2018; Moon 2015). Although the overall impact of oximes on patient outcomes has been questioned, the use of pralidoxime, in conjunction with atropine, is recommended (Blumenberg 2018; Howland 2018).

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

Medication Safety Issues
Sound-alike/look-alike issues:

Pralidoxime may be confused with pramoxine, pyridoxine

Protopam may be confused with protamine

Metabolism/Transport Effects

None known.

Drug Interactions

There are no known significant interactions.

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).

Breastfeeding Considerations

It is not known if pralidoxime is excreted in breast milk. The manufacturer recommends that caution be exercised when administering pralidoxime to nursing women.

Monitoring Parameters

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

Mechanism of Action

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

Pharmacokinetics (Adult Data Unless Noted)

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

Protein binding: None

Metabolism: Hepatic

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

Time to peak, serum: IV: 5 to 15 minutes; IM: ~35 minutes

Excretion: Urine (80% as metabolites and unchanged drug)

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

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

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AR) Argentina: Contrathion;
  • (BD) Bangladesh: Pradox | Pralidox;
  • (BR) Brazil: Contrathion;
  • (CN) China: Pralidoxime;
  • (CO) Colombia: Contrathion;
  • (EE) Estonia: Contrathion;
  • (FR) France: Contrathion;
  • (GB) United Kingdom: Protopam chloride;
  • (GR) Greece: Contrathion;
  • (IN) India: Cbc pam | Clopam | Lyphe;
  • (IT) Italy: Contrathion;
  • (JP) Japan: Pam;
  • (KR) Korea, Republic of: Newpudox | Pam-a | Pamu;
  • (LT) Lithuania: Neopam;
  • (NO) Norway: Contrathion;
  • (PL) Poland: Contrathion;
  • (PR) Puerto Rico: Protopam;
  • (SA) Saudi Arabia: Protopam chloride;
  • (TH) Thailand: Neopam | Pralidoxime chloride 2 pam asian pharm;
  • (TN) Tunisia: Contrathion;
  • (TW) Taiwan: Pam | Pamcl | Pampara
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Topic 9802 Version 132.0

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