U.S. Brand Names

• Protopam®

Medication Safety Issues

Sound-alike/look-alike issues:

• Pralidoxime may be confused with pramoxine, pyridoxine
• Protopam® may be confused with protamine, Protropin®

Generic Available

No

Pharmacologic Categories

• Antidote

Related Terms

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

Available Products

Image	Description
	Brand Name Protopam® Strength 1 g Labeler Wyeth Pharmaceuticals Class Rx Route for injection NDC 000460374
	Brand Name Protopam® Strength 1 g Labeler Baxter Healthcare Class Rx Route for injection NDC 006410374
	Strength 300 mg/mL Labeler Meridian Medical Technologies Inc Class Rx Route for injection NDC 117040251
	Brand Name Protopam® Strength 1 g Labeler Baxter Healthcare Class Rx Route for injection NDC 609770141

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)

Unlabeled/Investigational Use

Treatment of nerve agent toxicity (chemical warfare) in combination with atropine

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)

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.

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.

Dosing: Adults

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): Initial: 30 mg/kg over 20 minutes, maintenance: I.V. infusion: 4-8 mg/kg/hour

Treatment of acetylcholinesterase inhibitor toxicity: 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).
• 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)

Dosing: Elderly

Refer to adult dosing. Dosing should be cautious, considering possibility of decreased hepatic, renal, or cardiac function.

Nerve agent toxicity management (unlabeled use): To be effective, pralidoxime must be administered within minutes to a few hours following exposure (depending on the nerve agent). Also see “Note” in adult dosing.

• 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

Dosing: Pediatric

Organic phosphorus poisoning: I.V. (may be given I.M. or SubQ if I.V. is not feasible): 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

• Note: Use in conjunction with atropine; atropine effects should be established before pralidoxime is administered

Nerve agent toxicity management (unlabeled use): To be effective, pralidoxime must be administered within minutes to a few hours following exposure (depending on the nerve agent). Also see “Note” in adult dosing.

• 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)

Dosing: Renal Impairment

Dose should be reduced.

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]

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.

Pregnancy Risk Factor

C

Lactation

Excretion in breast milk unknown/not recommended

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)

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

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.

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 SWFI. 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.

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.

• 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.  [PMID:3418775]
• Ekins BR and Geller RJ, “Methomyl-Induced Carbamate Poisoning Treated With Pralidoxime Chloride,” West J Med, 1994, 161(1):68-70.  [PMID:7941519]
• 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.  [PMID:2319410]
• Jovanovic D, “Pharmacokinetics of Pralidoxime Chloride. A Comparative Study in Healthy Volunteers and in Organophosphorus Poisoning,” Arch Toxicol, 1989, 63(5):416-8.  [PMID:2818204]
• Kurtz PH, “Pralidoxime in the Treatment of Carbamate Intoxication,” Am J Emerg Med, 1990, 8(1):68-70.  [PMID:2403479]
• “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.  [PMID:12628894]
• 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. [PMID:12949297]