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Pronunciation
(pra li DOKS eem)
Generic Available (U.S.)
No
Index Terms
Brand Names: U.S.
Pharmacologic Category
Use: Labeled Indications
Treatment of muscle weakness and/or respiratory depression secondary to poisoning due to organophosphate anticholinesterase pesticides and chemicals (eg, nerve agents); control of overdose of anticholinesterase medications used to treat myasthenia gravis (ambenonium, neostigmine, pyridostigmine)
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).
Lactation
Excretion in breast milk unknown/use caution
Contraindications
There are no absolute contraindications listed within the manufacturer's labeling.
Warnings/Precautions
Disease-related concerns:
• Carbamate poisoning: Pralidoxime is not indicated for the treatment of carbamate poisoning; 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 should be treated with 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.
Adverse Reactions
Frequency not defined.
Cardiovascular: Cardiac arrest, hypertension, tachycardia
Central nervous system: Dizziness, drowsiness, headache, seizure
Dermatologic: Rash
Gastrointestinal: Nausea
Hepatic: ALT increased (transient), AST increased (transient)
Local: Pain at injection (I.M. administration)
Neuromuscular & skeletal: CPK increased, fasciculations, muscle rigidity, paralysis, weakness
Ocular: Accommodation impaired, blurred vision, diplopia
Renal: Renal function decreased
Respiratory: Apnea, hyperventilation, laryngospasm
Metabolism/Transport Effects
None known.
Drug Interactions
There are no known significant interactions.
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).
Reconstitution
I.V. administration: Dilute 1 g with 20 mL SWFI (50 mg/mL). The solution should be further diluted with NS to a final concentration of 10-20 mg/mL. If this is not practical or in cases of fluid overload, may prepare and administer as a 50 mg/mL solution.
I.M. administration: Dilute 1 g with 3.3 mL SWFI (300 mg/mL)
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
Pharmacodynamics/Kinetics
Distribution: Vdss: 0.6-2.7 L/kg; may increase with increasing severity of organophosphate intoxication (~9 L/kg in a severely poisoned pediatric patients; Schexnayder, 1998)
Protein binding: None
Metabolism: Hepatic
Half-life elimination: Apparent: 74-77 minutes; Poisoned patients (I.M., I.V.): 3-4 hours
Time to peak, serum: I.V.: 5-15 minutes; I.M.: ~35 minutes
Excretion: Urine (~80% as metabolites and unchanged drug)
Dosage
I.V.: Use in conjunction with atropine; atropine effects should be established before pralidoxime is administered.
Anticholinesterase poisoning (eg, neostigmine, pyridostigmine): Adults: 1000-2000 mg; followed by increments of 250 mg every 5 minutes as needed
Organophosphate poisoning: Note: May be given I.M. or SubQ if I.V. administration is not feasible:
Children ≤16 years: Loading dose: 20-50 mg/kg (maximum: 2000 mg/dose); Maintenance infusion: 10-20 mg/kg/hour; alternatively, a repeat bolus of 20-50 mg/kg (maximum: 2000 mg/dose) may be administered after 1 hour and repeated every 10-12 hours thereafter, as needed
Children >16 years and Adults: Loading dose: 1000-2000 mg; Maintenance: Repeat bolus of 1000-2000 mg after 1 hour and repeated every 10-12 hours thereafter, as needed. Alternatively, administer a loading dose of 30 mg/kg followed by a maintenance infusion of 8 mg/kg/hour (unlabeled dose; Roberts, 2007).
I.M.: Organophosphate poisoning: Note: Use in conjunction with atropine; atropine effects should be established before pralidoxime is administered. Consider I.M. or SubQ administration when I.V. administration is not feasible:
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 Adults:
Mild symptoms: 600 mg; repeat as needed for persistent mild symptoms every 15 minutes to a maximum total dose of 1800 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 1800 mg
Persistent symptoms: May repeat the entire series (1800 mg) beginning ~1 hour after administration of the last injection
Elderly: Refer to adult dosing; dosing should be cautious, considering possibility of decreased hepatic, renal, or cardiac function
Dosing adjustment in renal impairment: Dose should be reduced; no specific recommendations are provided by the manufacturer
Administration: I.M.
May administer I.M. if I.V. administration is not feasible.
Administration: I.V.
Loading dose: Infuse as a 10-20 mg/mL solution over 15-30 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 over ≥5 minutes.
Maintenance dose: Administer as a continuous or intermittent infusion at a rate not to exceed 200 mg/minute.
Administration: Other
May administer SubQ if I.V. administration is not feasible.
Monitoring Parameters
Heart rate, respiratory rate, muscle fasciculations and strength, pulse oximetry; cardiac monitor and blood pressure monitor required for I.V. administration
Cardiovascular Considerations
Use I.V. phentolamine for treatment of pralidoxime-induced hypertension (children: 1 mg; adults: 5 mg).
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness or drowsiness
Mental Health: Effects on Psychiatric Treatment
Avoid with phenothiazines; effects of barbiturates may be increased
Nursing: Physical Assessment/Monitoring
Monitor vital signs, blood pressure, and respiratory status on a frequent basis. Continuous ECG and hemodynamic monitoring is necessary. Monitor fluid balance throughout therapy (oliguria). With organophosphate poisoning or anticholinesterase overdose, monitor closely for muscle weakness or twitching, reduction in respiratory function, or altered consciousness. Keep under observation for 48-72 hours.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution, as chloride:
Protopam®: 1 g
Injection, solution, as chloride: 300 mg/mL (2 mL)
References
Agency for Toxic Substances and Disease Registry (ATSDR), “Medical Management Guidelines for Nerve Agents: Tabun (GA); Sarin (GB); Soman (GD); and VX,” August, 2008. Available at http://www.atsdr.cdc.gov/mhmi/mmg166.pdf
de Kort WL, Kiestra SH, and Sangster B, “The Use of Atropine and Oximes in Organophosphate Poisoning: A Modified Approach,” J Toxicol Clin Toxicol, 1988, 26(3-4):199-208.
Ekins BR and Geller RJ, “Methomyl-Induced Carbamate Poisoning Treated With Pralidoxime Chloride,” West J Med, 1994, 161(1):68-70.
Farrar HC, Wells TG, and Kearns GL, “Use of Continuous Infusion of Pralidoxime for Treatment of Organophosphate Poisoning in Children,” J Pediatr, 1990, 116(4):658-61.
Jovanovic D, “Pharmacokinetics of Pralidoxime Chloride. A Comparative Study in Healthy Volunteers and in Organophosphorus Poisoning,” Arch Toxicol, 1989, 63(5):416-8.
Kamha AA, Al Omary IY, Zalabany HA, et al, "Organophosphate Poisoning in Pregnancy: A Case Report," Basic Clin Pharmacol Toxicol, 2005, 96(5):397-8.
Kurtz PH, “Pralidoxime in the Treatment of Carbamate Intoxication,” Am J Emerg Med, 1990, 8(1):68-70.
“Medical Management Guidelines (MMGs) for Nerve Agents: Tabun (GA); Sarin (GB); Soman (GD); and VX.” Available at http://www.atsdr.cdc.gov/mmg/mmg.asp?id=523&tid=93
Medicis JJ, Stork CM, Hoffman RS, et al, “Improved 2-PAM Dosing Regimen in Human Volunteers: A Pharmacokinetic Study,” Vet Hum Toxicol, 1994, 36:377.
Mokhlesi B, Leikin JB, Murray P, et al, “Adult Toxicology in Critical Care: Part II: Specific Poisonings,” Chest, 2003, 123(3):897-922.
Murphy M and Desai H, “Pralidoxime-Induced Laryngospasm,” Vet Hum Toxicol, 1994, 36:375.
Roberts DM and Aaron CK, “Management of Acute Organophosphorus Pesticide Poisoning,” BMJ, 2007, 334(7594):629-34.
Rotenberg JS and Newmark J, "Nerve Agent Attacks on Children: Diagnosis and Management," Pediatrics, 2003, 112(3 Pt 1):648-58.
Schexnayder S, James LP, Kearns GL, et al, “The Pharmacokinetics of Continuous Infusion Pralidoxime in Children With Organophosphate Poisoning,” J Toxicol Clin Toxicol, 1998, 36(6):549-55.
International Brand Names
Lexi-Comp.com
Last full review/revision February 2012
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