Pralidoxime Chloride

Pronunciation: PRAL-i-DOX-eem KLOR-ide
Class: Antidote

Trade Names

Protopam Chloride
- Injection, powder for solution 1 g

Pharmacology

Reactivates cholinesterase (mainly outside of the CNS) that has been inactivated by phosphorylation because of an organophosphate pesticide or related compound; also slows the process of aging of phosphorylated cholinesterase to a nonreactivatable form, and detoxifies certain organophosphates by direct chemical reaction.

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Pharmacokinetics

Absorption

Short acting. IM C max and T max are approximately 7.5 mcg/mL and 34 min (healthy patients) and 9.8 mcg/mL and 33 min (poisoned patients), respectively.

Distribution

Apparent Vd at steady state is 0.6 to 2.7 L/kg. Not bound to plasma proteins.

Elimination

Rapidly excreted in the urine by renal tubular secretion, partly unchanged, and partly as a metabolite produced by the liver. Apparent half-life is 74 to 77 min; mean half-life is 3 h; elimination half-life is 4 h.

Special Populations

Renal Function Impairment

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

Hepatic Function Impairment

No data are available.

Children

Vd and half-life are 1.7 to 13.8 L/kg and 2.4 to 5.3 h, respectively.

Indications and Usage

For the control of overdosage by anticholinesterase drugs used in the treatment of myasthenia gravis; as an antidote in the treatment of poisoning caused by those pesticides and chemicals (eg, nerve agents) of the organophosphate class that have anticholinesterase activity.

Contraindications

Known hypersensitivity to the drug and other situations in which the risk of its use clearly outweighs possible benefit.

Dosage and Administration

Anticholinesterase overdose
Adults

IV 1 to 2 g followed by increments of 250 mg every 5 min.

Organophosphate poisoning
Adults IV

1 to 2 g infusion initially. If this is not practical or if pulmonary edema is present, give the dose slowly by IV injection. After approximately 1 h, a second dose of 1 to 2 g may be indicated if muscle weakness has not been relieved. Additional doses may be given every 10 to 12 h, cautiously, if muscle weakness persists.

IM

For mild symptoms, administer 600 mg. Wait 15 min. After 15 min, if mild symptoms persist, administer a second dose. If, after an additional 15 min, mild symptoms continue to persist, administer a third dose for a total cumulative dose of 1,800 mg. If at any time after the first dose the patient develops severe symptoms, administer 2 additional 600 mg doses in rapid succession for a total cumulative dose of 1,800 mg. For treatment of severe symptoms, administer three 600 mg doses in rapid succession for a total dose of 1,800 mg. If symptoms persist after administering the complete 1,800 mg regimen, the series may be repeated beginning approximately 1 h after administration of the last injection.

Children IV Continuous infusion

20 to 50 mg/kg (not to exceed 2g/dose) loading dose followed by a continuous infusion of 10 to 20 mg/kg/h.

Intermittent infusion

20 to 50 mg/kg (not to exceed 2g/dose) initially. A second dose of 20 to 50 mg/kg may be indicated after approximately 1 h if muscle weakness has not been relieved. Repeat dosing is permissible every 10 to 12 h as needed.

IV injection

If it is not practical to administer intermittent or continuous infusions, or if pulmonary edema is present, the 20 to 50 mg/kg dose should be given by IV injection. Additional doses may be given every 10 to 12 h if muscle weakness persists.

IM

For treatment of mild symptoms, administer 15 mg/kg if child weighs less than 40 kg or 600 mg if the child weighs 40 kg or more. Wait 15 min. After 15 min, if mild symptoms persist, administer a second dose. If, after an additional 15 min, mild symptoms continue to persist, a third dose may be administered (max per total 3-injection course, 45 mg/kg if the child weighs less than 40 kg or 1800 mg if the child weighs 40 kg or more). If at any time after the first dose the patient develops severe symptoms, administer 2 additional doses in rapid succession. If symptoms persist after administering a complete course (3 injections), the series may be repeated beginning approximately 1 h after administration of the last injection.

Concomitant therapy

Give atropine as soon as possible after hypoxemia is improved. Do not give atropine in the presence of significant hypoxia because of the risk of atropine-induced ventricular fibrillation. In adults, atropine may be given IV in doses of 2 to 4 mg. Repeat this at 5- to 10-min intervals until full atropinization (secretions are inhibited) or signs of atropine toxicity appear (delirium, hyperthermia, muscle twitching). Maintain some degree of atropinization for at least 48 h and until any depressed blood cholinesterase activity is reversed. After the effects of atropine become apparent, pralidoxime may be administered.

Renal function impairment

Reduce dose.

General Advice

  • Administration should be carried out slowly over 15 to 30 min, preferably by infusion. If IV administration is not feasible, use IM or IV injection over no less than 5 min.
  • Intermittent infusion rate should not exceed 200 mg/min.
  • IM injections for children should be administered in the anterolateral aspect of the thigh to avoid the nerve, artery, and vein, as well as the femur.
  • For organophosphate poisoning in adults, evidence suggests that a loading dose followed by continuous IV infusion of pralidoxime may maintain therapeutic levels longer than traditional short intermittent infusion therapy.
  • For IV use, reconstitute a single 1 g vial by adding 20 mL of sterile water for injection, which results in a 50 mg/mL concentration. The solution should be further diluted with normal saline to achieve a concentration of 10 to 20 mg/mL (eg, 1 g in 100 mL or 2 g in 100 mL).
  • For IV injection, reconstitute a single 1 g vial by adding 20 mL of sterile water for injection, which results in a concentration of 50 mg/mL.
  • For IM use, reconstitute a single pralidoxime 1 g vial by adding 3.3 mL of sterile water for injection, which results in an approximate concentration of 300 mg/mL.
  • Visually inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit.
  • Pralidoxime is most effective if administered immediately after organophosphate poisoning. Generally, little is accomplished if the drug is given more than 36 h after termination of exposure. When the poison has been ingested, however, exposure may continue for some time because of slow absorption from the lower bowel, and fatal relapses have been reported after initial improvement. Close supervision of the patient is indicated for at least 48 to 72 h.
  • If dermal exposure to an organophosphate has occurred, remove clothing and wash the hair and skin thoroughly with sodium bicarbonate or alcohol as soon as possible.
  • Treatment should include general supportive care, atropinization, and decontamination, in addition to the use of pralidoxime. Supportive care, including airway management, respiratory and CV support, correction of metabolic abnormalities, and seizure control, may be necessary in cases of severe organophosphate poisoning.

Storage/Stability

Store between 59° and 77°F. Discard unused solution after a dose has been withdrawn.

Drug Interactions

Atropine

Signs of atropinization (eg, flushing, mydriasis, tachycardia, dryness of the mouth and nose) may occur earlier than might be expected when atropine is used alone, especially if the total dose of atropine has been large and the administration of pralidoxime has been delayed. Closely monitor the clinical response.

Adverse Reactions

Cardiovascular

Cardiac arrest, hypertension, tachycardia.

CNS

Convulsions, dizziness, drowsiness, headache.

Lab Tests

AST and/or ALT elevations, elevated creatine phosphokinase.

Musculoskeletal

Muscle fasciculations, rigidity, or weakness; paralysis.

Respiratory

Apnea, hyperventilation, laryngospasm.

Special Senses

Blurred vision, diplopia, impaired accommodation.

Miscellaneous

Mild to moderate pain at injection site, nausea.

Precautions

Monitor

Institute treatment of organophosphate poisoning without waiting for the results of laboratory tests. Red blood cell, plasma cholinesterase, and urinary paranitrophenol measurements (in the case of parathion exposure) may be helpful in confirming the diagnosis and following the course of the illness. A reduction in red blood cell cholinesterase concentration to below 50% of normal has been seen only with organophosphate ester poisoning.


Pregnancy

Category C .

Lactation

Undetermined.

Elderly

Dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Renal Function

Because pralidoxime is excreted in the urine, a decrease in renal function will result in increased blood levels of the drug. Thus, reduce the dosage in the presence of renal insufficiency.

Myasthenia gravis

Use with great caution in treating organophosphate overdosage in cases of myasthenia gravis because it may precipitate a myasthenic crisis.

Other poisonings

Not effective in the treatment of poisoning caused by phosphorus, inorganic phosphates, or organophosphates not having anticholinesterase activity; not indicated as an antidote for intoxication by pesticides of the carbamate class because it may increase the toxicity of carbaryl.

Overdosage

Symptoms

Blurred vision, diplopia, dizziness, headache, impaired accommodation, nausea, slight tachycardia.

Patient Information

  • Advise patient, family, or caregiver that medication will be prepared and administered by health care provider in a health care setting.
  • Advise patient, family, or caregiver to immediately report any of the following to the health care provider: excessive salivation, nausea, or vomiting; injection-site reaction or pain.

Copyright © 2009 Wolters Kluwer Health.

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