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Medication Safety Issues
Sound-alike/look-alike issues:
Pralidoxime may be confused with pramoxine, pyridoxine
Protopam® may be confused with Proloprim®, protamine, Protropin®
Pronunciation
(pra li DOKS eem)
U.S. Brand Names
Index Terms
Generic Available
No
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Reverse muscle paralysis caused by toxic exposure to organophosphate acetylcholinesterase-inhibiting pesticides and chemicals; control of overdose of acetylcholinesterase medications used to treat myasthenia gravis (ambenonium, neostigmine, pyridostigmine)
Use: Unlabeled/Investigational
Treatment of nerve agent toxicity (chemical warfare) in combination with atropine
Pregnancy Risk Factor
C
Lactation
Excretion in breast milk unknown/not recommended
Contraindications
Hypersensitivity to pralidoxime or any component of the formulation; poisonings due to phosphorus, inorganic phosphates, or organic phosphates without anticholinesterase activity; poisonings due to pesticides of carbamate class (may increase toxicity of carbaryl)
Warnings/Precautions
Disease-related concerns:
• Myasthenia gravis: Use with caution in patients with myasthenia gravis.
• Renal impairment: Use with caution in patients with renal impairment; dosage modification required.
Other warnings/precautions:
• Appropriate use: Clinical symptoms consistent with highly-suspected organophosphorous poisoning should be treated with antidote immediately; administration should not be delayed for confirmatory laboratory tests. Treatment should always include proper evacuation and decontamination procedures; medical personnel should protect themselves from inadvertent contamination. Antidotal administration is intended only for initial management; definitive and more extensive medical care is required following administration. Individuals should not rely solely on antidote for treatment, as other supportive measures (eg, artificial respiration) may still be required.
Adverse Reactions
Frequency not defined.
Cardiovascular: Hypertension, tachycardia
Central nervous system: Dizziness, drowsiness, headache
Dermatologic: Rash
Gastrointestinal: Nausea
Hepatic: ALT increased (transient), AST increased (transient)
Local: Pain at injection site after I.M. administration
Neuromuscular & skeletal: Muscle rigidity, weakness
Ocular: Accommodation impaired, blurred vision, diplopia
Renal: Renal function decreased
Respiratory: Hyperventilation, laryngospasm
Drug Interactions
There are no known significant interactions.
Storage
Store at controlled room temperature of 20°C to 25°C (68°F to 77°F).
Reconstitution
For I.V. administration, dilute 1 g with 20 mL SWI. Solution should be further diluted and administered as 1-2 g in 100 mL NS. If not practical or in cases of fluid overload, may prepare as a 5% solution.
Mechanism of Action
Reactivates cholinesterase that had been inactivated by phosphorylation due to exposure to organophosphate pesticides by displacing the enzyme from its receptor sites; removes the phosphoryl group from the active site of the inactivated enzyme
Pharmacodynamics/Kinetics
Protein binding: None
Metabolism: Hepatic
Half-life elimination: 74-77 minutes
Time to peak, serum: I.V.: 5-15 minutes
Excretion: Urine (80% to 90% as metabolites and unchanged drug)
Dosage
Organic phosphorus poisoning (use in conjunction with atropine; atropine effects should be established before pralidoxime is administered): I.V. (may be given I.M. or SubQ if I.V. is not feasible):
Children: 20-50 mg/kg/dose; repeat in 1-2 hours if muscle weakness has not been relieved, then at 8- to 12-hour intervals if cholinergic signs recur
Adults: Initial: 30 mg/kg over 20 minutes, maintenance: I.V. infusion: 4-8 mg/kg/hour
Treatment of acetylcholinesterase inhibitor toxicity: Adults: I.V.: Initial: 1-2 g followed by increments of 250 mg every 5 minutes until response is observed
Nerve agent toxicity management (unlabeled use): Note: Atropine is a component of the management of nerve agent toxicity; consult atropine monograph for specific route and dose. To be effective, pralidoxime must be administered within minutes to a few hours following exposure (depending on the nerve agent).
Infants and Children:
Prehospital (“in the field”): Mild-to-moderate symptoms: I.M.: 15 mg/kg; severe symptoms: 25 mg/kg
Hospital/emergency department: Mild-to-severe symptoms: I.V.: 15 mg/kg (up to 1 g)
Adults:
Prehospital (“in the field”): Mild-to-moderate symptoms: I.M.: 600 mg; severe symptoms: 1800 mg
Hospital/emergency department: Mild-to-severe symptoms: I.V.: 15 mg/kg (up to 1 g)
Frail patients, elderly:
Prehospital (“in the field”): Mild-to-moderate symptoms: I.M.: 10 mg/kg; severe symptoms: 25 mg/kg
Hospital/emergency department: Mild-to-severe symptoms: I.V.: 5-10 mg/kg
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
Administration: I.V.
I.V.: Infuse over 15-30 minutes at a rate not to exceed 200 mg/minute; may administer I.M. or SubQ if I.V. is not accessible. If a more concentrated 5% solution is used, infuse over at least 5 minutes.
Monitoring Parameters
Heart rate, respiratory rate, blood pressure, continuous ECG; cardiac monitor and blood pressure monitor required for I.V. administration
Reference Range
Minimum therapeutic concentration: 4 mcg/mL
Patient Education
When administered in emergency situation, patient education and instruction should be appropriate to patient condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Breast-feeding is not recommended.
Additional Information
Pralidoxime is most effective when given immediately after poisoning. If the poison has been ingested, exposure may continue due to slow absorption from the lower bowel; relapses may occur after initial improvement and treatment may need continued for several days in these patients. In cases of dermal exposure to organophosphate poisoning, clothing should be removed and hair and skin washed with sodium bicarbonate or alcohol as soon as possible.
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: Use I.V. phentolamine for treatment of pralidoxime-induced hypertension (children: 1 mg; adults: 5 mg).
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. 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: 300 mg/mL (2 mL) [contains benzyl alcohol; prefilled auto injector]
References
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.
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: www.atsdr.cdc.gov/MHMI/mmg166.html. Accessed January 8, 2003.
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.
Rotenberg JS and Newmark J, "Nerve Agent Attacks on Children: Diagnosis and Management," Pediatrics, 2003, 112(3 Pt 1):648-58.
International Brand Names
Lexi-Comp.com
Last full review/revision August 2009
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