Pralidoxime (Monograph)

Brand names: ATNAA, DuoDote, Protopam
Drug class: Antidotes
- Cholinesterase Reactivators
ATC class: V03AB04
VA class: AD900
CAS number: 51-15-0

Medically reviewed by Drugs.com on Jan 23, 2023. Written by ASHP.

Introduction

Cholinesterase reactivator; quaternary ammonium oxime.

Uses for Pralidoxime

Pesticide Poisoning

Concomitantly with atropine to reverse muscle paralysis (particularly of respiratory muscles) associated with toxic exposure to organophosphate anticholinesterase pesticides.

Atropine is used to reverse muscarinic effects associated with toxic exposure to carbamate anticholinesterase pesticides; concomitant pralidoxime therapy is usually not necessary.

Chemical Warfare Agent Poisoning

Concomitantly with atropine for the treatment of nerve agent (e.g., sarin, soman, tabun, VX [methylphosphonothioic acid]) exposure in the context of chemical warfare or terrorism.

Initial management of nerve agent poisoning includes aggressive airway control and ventilation (administration of nebulized β-adrenergic agonist [e.g., albuterol] and antimuscarinics [e.g., ipratropium bromide] may be necessary), and administration of atropine and pralidoxime chloride; diazepam may be needed for seizure control.

Anticholinesterase Overdose

Has been used for the management of overdosage of anticholinesterase agents (ambenonium, neostigmine, pyridostigmine) in patients with myasthenia gravis.

Pralidoxime Dosage and Administration

General

Pesticide Poisoning

• Dose based on severity of symptoms and treatment setting.

• Mild symptoms include miosis or blurred vision, tearing, runny nose, hypersalivation or drooling, wheezing, muscle fasciculations, nausea/vomiting.

• Severe symptoms include behavioral changes, severe breathing difficulty, severe respiratory secretions, severe muscle twitching, involuntary defecation or urination, seizures, unconsciousness.

Chemical Warfare Agent Poisoning

• Dose and route based on severity of symptoms, victim's age, and treatment setting.

• Mild to moderate symptoms include localized sweating, muscle fasciculations, nausea, vomiting, weakness, and/or dyspnea.

• Severe symptoms include apnea, flaccid paralysis, seizures, and/or unconsciousness.

Administration

Administer by IM or IV injection, or by IV infusion.

Available as a single-entity preparation (pralidoxime chloride for injection, pralidoxime chloride injection auto-injector) and as a preparation containing atropine and pralidoxime chloride (DuoDote auto-injector, ATNAA auto-injector).

Pesticide poisoning: Most effective if administered early; may still be effective if administered >48 hours after exposure.

Chemical warfare agent poisoning: Administer within minutes to a few hours following exposure.

IV Administration

IV infusion is preferred; slow IV injection used in patients with pulmonary edema, if IV infusion is not practical, or if rapid effect is needed.

Reconstitution

Reconstitute vials containing 1 g of pralidoxime chloride by adding 20 mL of sterile water for injection to provide a solution containing approximately 50 mg/mL.

Dilution

For IV infusion, dilute appropriate volume of reconstituted solution in 100 mL of 0.9% sodium chloride injection.

Rate of Administration

IV infusion: Administer over 15–30 minutes in adults. Administer over 30 minutes in children.

SlowIV injection as solution containing 50 mg/mL: Administer over ≥5 minutes. Administration at a rate ≥200 mg/minute can lead to respiratory and cardiac arrest.

IM Administration

Preparation Considerations

Pralidoxime chloride auto-injector: Intended for self-administration or administration by a partner (buddy) by military personnel. Also may be administered by civilian emergency responders.

Pralidoxime chloride and atropine (DuoDote) auto-injector: Intended for administration by emergency medical service personnel.

Pralidoxime chloride and atropine (ATNAA) auto-injector: Intended for self-administration or administration by partner (buddy) by military personnel.

Technique for Using Auto-injector

Pralidoxime chloride auto-injector: Inject dose IM into the anterolateral aspect of the thigh.

Pralidoxime chloride auto-injector: Remove gray safety cap; place black end on outer thigh and push until injector functions; hold in place for 10 seconds until dose is delivered. Massage injection area for several seconds.

DuoDote: Inject dose IM into the anterolateral aspect of the thigh.

DuoDote: Grasp the prefilled auto-injector with the green tip pointed downward; remove the gray activation (safety) cap. Point the green tip toward the outer thigh and jab it firmly into the outer thigh so that the auto-injector is perpendicular (90° angle) to the thigh, and hold firmly in the thigh for at least 10 seconds until the dose is delivered. Remove auto-injector and check green tip; if needle is visible, dose has been administered. If the needle is not exposed, check that the safety cap was removed and repeat administration but press harder.

ATNAA: Inject dose IM into the anterolateral aspect of the thigh or into the buttock.

ATNAA: Remove gray safety cap; place front end on outer thigh or buttock and push until injector functions; hold in place for 10 seconds until dose is delivered.

Administer through clothing if necessary.

After use, bend needle back against a hard surface and dispose of properly.

Reconstitution

If pralidoxime chloride for injection is used for an IM dose, reconstitute a vial containing 1 g of drug with 3 mL of sterile water for injection or 0.9% sodium chloride for injection to provide a solution containing 300 mg/mL.

Dosage

Available as pralidoxime chloride; dosage expressed in terms of the salt.

Administer pralidoxime after atropine.

Each prefilled DuoDote auto-syringe and each prefilled ATNAA auto-syringe provides a single IM dose of atropine 2.1 mg and pralidoxime chloride 600 mg. When activated, the auto-injector sequentially administers atropine and pralidoxime chloride through a single needle.

Pediatric Patients

Pesticide Poisoning† [off-label]

Organophosphate Anticholinesterase Pesticides

IV

Usual initial dose: 20–40 mg/kg; may repeat in 1 hour if muscle weakness not relieved. Additional doses may be needed.

Chemical Warfare Agent Poisoning† [off-label]

Organophosphate Anticholinesterase Nerve Agents

Administer IV in emergency department.

Administer IM in out-of-hospital setting.

IV

Children 0–10 years of age and adolescents >10 years of age who present with mild/moderate symptoms or severe symptoms: 15 mg/kg.

IM

Children 0–10 years of age and adolescents >10 years of age who present with mild/moderate symptoms: 15 mg/kg.

Children 0–10 years of age and adolescents >10 years of age who present with severe symptoms: 25 mg/kg.

Adults

Pesticide Poisoning

Organophosphate Anticholinesterase Pesticides

IV

Usual initial dose: 1–2 g; may repeat in 1 hour if muscle weakness not relieved. Additional doses may be needed.

Alternatively, 500 mg/hr as continuous IV infusion.

IM

DuoDote: For ≥2 mild symptoms, inject contents of 1 auto-injector (atropine 2.1 mg and pralidoxime chloride 600 mg). If severe symptoms develop, inject 2 additional doses (i.e., contents of 2 auto-injectors) in rapid succession.

DuoDote: For severe symptoms, inject contents of 3 auto-injectors (total dose: atropine 6.3 mg and pralidoxime chloride 1800 mg) in rapid succession.

Additional doses (i.e., >3) should not be administered unless definitive medical care is available.

Chemical Warfare Agent Poisoning

Organophosphate Anticholinesterase Nerve Agents

Administer IV in emergency department.

Administer IM in out-of-hospital setting.

IV

Adults who present with mild/moderate symptoms or severe symptoms: 15 mg/kg (up to 1 g).

IM

Adults who present with mild/moderate symptoms: 600 mg.

Adults who present with severe symptoms: 1800 mg.

Pralidoxime chloride auto-injector: Following atropine administration, pralidoxime chloride 600 mg. If symptoms are still present after 15 minutes, repeat injections. If symptoms remain after an additional 15 minutes, repeat injections. If symptoms persist after the third dose, seek medical attention.

DuoDote, ATNAA: For ≥2 mild symptoms, inject contents of 1 auto-injector (atropine 2.1 mg and pralidoxime chloride 600 mg). If severe symptoms develop, inject 2 additional doses (i.e., contents of 2 auto-injectors) in rapid succession.

DuoDote, ATNAA: For severe symptoms, inject contents of 3 auto-injectors (total dose: atropine 6.3 mg and pralidoxime chloride 1800 mg) in rapid succession.

Additional doses (i.e., >3) should not be administered unless definitive medical care is available.

Anticholinesterase Overdose

IV

1–2 g initially, followed by 250 mg every 5 minutes.

Prescribing Limits

Adults

Pesticide Poisoning and Chemical Warfare Agent Poisoning

IV

Maximum rate of administration: 200 mg/minute.

IM

Out-of-hospital setting: Maximum 3 doses (total 1800 mg). Additional doses require medical supervision (e.g., hospitalization, respiratory support).

Special Populations

Renal Impairment

Reduce dosage in patients with renal impairment.

Geriatric Patients

When used for the treatment of nerve agent poisoning in frail geriatric patients with mild to moderate symptoms in an out-of-hospital setting, the usual IM dose is 10 mg/kg. The usual IM dose for those with severe symptoms is 25 mg/kg.

When used for the treatment of nerve agent poisoning in frail geriatric patients with mild to moderate or severe symptoms in an emergency room, the usual IV dose is 5–10 mg/kg.

Select dosage with caution (generally starting at the low end of the dosage range) because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Cautions for Pralidoxime

Contraindications

• No absolute contraindications to use in life-threatening conditions (e.g., poisoning by organophosphate nerve agents and pesticides).

• Relative contraindications include hypersensitivity to pralidoxime or any component of the product.

Warnings/Precautions

Warnings

When used concomitantly with atropine, consider the cautions, precautions, and contraindications associated with atropine.

Not effective in the treatment of toxic exposure to phosphorus, inorganic phosphates, or organophosphates that do not possess anticholinesterase activity.

General Precautions

Concomitant Drug Therapy

Avoid administration of barbiturates, morphine, aminophylline, theophylline, succinylcholine, reserpine, or phenothiazines in patients with toxic exposures to acetylcholinesterase compounds.

Cardiovascular Effects

Hypertension reported. If possible, monitor BP during treatment.

Monitor cardiac rhythm.

Laboratory Monitoring

When organophosphate or nerve agent poisoning is known or suspected, initiate treatment without waiting for laboratory test results. The most useful test to confirm exposure is RBC cholinesterase activity. If this test is not available, measure plasma cholinesterase.

Myasthenia Gravis

Use with caution in patients with myasthenia gravis receiving anticholinesterase agents. May precipitate a myasthenic crisis.

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether pralidoxime is distributed into human milk. Caution advised.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

Pralidoxime chloride for injection: Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; select dose with caution. Dosage adjustment recommended in frail geriatric patients. (See Geriatric Patients under Dosage and Administration.)

Renal Impairment

Use with caution. (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Blurred vision, diplopia, impaired accommodation, headache, drowsiness, nausea, tachycardia, increased BP, hyperventilation, muscle weakness. Injection site pain following IM injection.

Pralidoxime Pharmacokinetics

Absorption

Bioavailability

Following IM administration, peak plasma concentrations achieved in about 28 minutes.

Distribution

Extent

Distributed to extracellular water and tissues.

Not known if pralidoxime is distributed into milk.

Plasma Protein Binding

Not bound to plasma proteins.

Elimination

Metabolism

Not completely known; however, believed to be metabolized in the liver.

Elimination Route

Excreted in urine as unchanged drug and as a metabolite.

Half-life

1–2.5 hours.

Stability

Storage

Parenteral

Powder for Injection

20–25°C (may be exposed to 15–30°C).

Injection

Auto-injector: 25°C (may be exposed to 15–30°C). Protect from freezing. Protect from light.

Actions

• Reactivates cholinesterase that has been recently inactivated by phosphorylation as the result of exposure to certain organophosphates (e.g., pesticide, nerve agent).

• Removes the phosphoryl group from the active site of the inhibited enzyme by nucleophilic attack, regenerating active cholinesterase and forming an oxime complex.

• Also detoxifies certain organophosphates by direct chemical reaction and may react directly with cholinesterase to protect it from inhibition.

• Must be administered before aging of the inhibited enzyme occurs. After aging is complete, phosphorylated cholinesterase cannot be reactivated.

Advice to Patients

• Seek immediate medical attention after injection with pralidoxime in an out-of-hospital setting.

• For IM administration in an out-of-hospital setting for nerve gas and pesticide poisoning, importance of ensuring adequate understanding of the recognition and treatment of such poisoning and when concomitant therapy may be necessary.

• For IM administration in an out-of-hospital setting for nerve gas and pesticide poisoning, importance of not exceeding 3 doses unless under medical supervision.

• Advise patients that primary protection against exposure to chemical nerve agents and pesticide poisoning is the wearing of protective garments (e.g., masks).

• For IM administration in an out-of-hospital setting for nerve gas and pesticide poisoning, proper techniques for storage, attention to expiration dating (replacing before expiration), use, and disposal of the prefilled auto-injector.

• For IM administration in an out-of-hospital setting for nerve gas and pesticide poisoning, importance of seeking immediate medical attention once the initial dose(s) is administered because respiratory and other supportive care may be needed.

• In the event of nerve gas and pesticide poisoning, importance of not contaminating other individuals (e.g., medical and emergency personnel) by clothing exposure; aggressive and safe decontamination by trained personnel is strongly suggested.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Pralidoxime chloride injection auto-injector is supplied through the Directorate of Medical Materiel, Defense Supply Center Philadelphia or other local, state or federal agency. ATNAA is supplied through the Directorate of Medical Materiel, Defense Supply Center Philadelphia. Duodote is available for hospitals and emergency responders through Meridian Medical Technology (800-638-8093).

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