Bedside Snapshot

Use It For
Organophosphate insecticide poisoning with weakness, fasciculations or paralysis; nerve agent exposure (with atropine); cholinesterase poisoning of unknown class; anticholinesterase drug overdose
Adult Dose
  • Organophosphate: 2 g IV over 15–30 min (do not bolus), then 1 g/hr (AHA 2025 Table 4)
  • Nerve agent field: 600 mg IM autoinjector: 1 if mild, 3 if severe (max 3 devices, then definitive care)
Pediatric Dose
Up to 40 kg or 14 years: 20–50 mg/kg IV over 15–30 min (max 2 g), then 10–20 mg/kg/hr. IM under 40 kg: 15 mg/kg (max 45 mg/kg per course). Over 40 kg or 14 years: adult dose. DuoDote only over 41 kg
Onset / Duration
IM: peak about 30 min; reaches the animal-derived minimum therapeutic level (4 mcg/mL) in about 16 min. IV: a 1 g dose falls below therapeutic in about 1.5 hr, so infuse or repeat. Strength returns slowly
Do Not Give / Hold If
No absolute contraindication in life-threatening poisoning. Known carbamate-only poisoning: no routine pralidoxime (label). Stop the load for laryngospasm, rigidity or apnea; never faster than 200 mg/min
Watch For
Laryngospasm, rigidity or arrest with fast IV (airway during the load); hypertension and tachycardia (BP, ECG); returning weakness from ongoing absorption (neck flexion, respiratory effort)
Reversal / Rescue
No antidote: stop the infusion and support the airway. Poor response: keep atropinizing, ventilate, and suspect aged enzyme or soman/tabun; call the poison center (1-800-222-1222)
Must Remember
Atropine first, pralidoxime early. Atropine treats the secretions that kill; pralidoxime only works before the enzyme ages, so give it with atropine, never instead of it.

Indications

Emergency & Prehospital

  • Nerve agent exposure (sarin, soman, tabun, VX) with symptoms: give with atropine by autoinjector as soon as symptoms appear. Against soman and tabun, expect limited benefit.
  • Organophosphate insecticide poisoning with nicotinic signs: fasciculations, weakness or respiratory muscle paralysis. These are the nicotinic signs. AHA 2025 rates pralidoxime reasonable for adults (Class 2a, LOE A) and children (Class 2a, LOE B-R) with life-threatening organophosphate poisoning. It sits alongside atropine, benzodiazepines and early intubation (Class 1).

ED / ICU / Transport

  • Moderate to severe organophosphate poisoning: IV load first, then a continuous infusion. Keep it running until clinical recovery.
  • Cholinesterase inhibitor poisoning of unknown class: can't tell an organophosphate from a carbamate? Don't withhold the oxime. That is AHA 2025 guidance.
  • Overdose of anticholinesterase drugs used in myasthenia gravis: neostigmine, pyridostigmine or ambenonium. This is labeled use, but it carries a risk of precipitating myasthenic crisis.

Other Uses

  • Known carbamate-only poisoning (e.g. carbaryl): don't give it routinely. Atropine and supportive care are the plan. AHA 2025 Part 10 finds the data insufficient to recommend for or against an oxime. Differs from FDA label: the Protopam label says it is not indicated for carbamate pesticides, because it may increase carbaryl toxicity.
  • Life-threatening carbamate poisoning: atropine is Class 1 (LOE A). Early intubation is Class 1 (C-LD adults, C-EO children). Benzodiazepines are Class 1 (C-EO). Diazepam is first line and midazolam is acceptable. Succinylcholine and mivacurium are Class 3: No Benefit (C-EO). AHA 2025 Part 10, recommendations 1–4 and 9
  • Not effective for phosphorus, inorganic phosphates or organophosphates that lack anticholinesterase activity
  • Ineffective or only marginally effective (label) against dimethoate, phorate, dimefox, methyl diazinon, methyl phencapton, Ciodrin, schradan and Wepsyn. Give atropine and supportive care anyway.

Dosing & Administration

Check where each dose comes from before you give it. The 2025 AHA CPR and ECC guidelines, Part 10 (Table 4), set adult IV dosing. Pediatric doses come from AHA/AAP 2025 when it states a dose. When it doesn't, the NASEMSO National Model EMS Clinical Guidelines v3.0 (2022) apply, then the US label. If none of them gives a dose, none is shown. A pediatric maximum never goes above the adult maximum (NASEMSO Universal Care Guideline, p. 13). Doses are off-label unless marked labeled. Differences from the FDA label are marked.

Available Forms

  • Protopam Chloride vial: 1 g lyophilized pralidoxime chloride per single-dose vial, reconstituted with 20 mL sterile water to 50 mg/mL; hospital stock and CHEMPACK hospital containers
  • DuoDote autoinjector (civilian EMS): atropine 2.1 mg/0.7 mL and pralidoxime chloride 600 mg/2 mL in two chambers, delivered through one needle; the form EMS carries
  • ATNAA autoinjector (military): same contents as DuoDote; labeled for adults
  • Pralidoxime chloride autoinjector: 600 mg/2 mL, the second device of the legacy military Mark I kit; still stocked in CHEMPACK containers
Mark I kit: AtroPen autoinjector numbered 1 and pralidoxime chloride autoinjector numbered 2, with training devices
Figure 1: Mark I Nerve Agent Antidote Kit: AtroPen atropine autoinjector (1) and pralidoxime chloride 600 mg autoinjector (2), with matching training devices. DuoDote and ATNAA now deliver both drugs through one needle, but Mark I pralidoxime autoinjectors remain in CHEMPACK stock. Source: Wikimedia Commons, US Army Medical Materiel Development Activity, public domain

Adult Dosing

IndicationDose & RouteRepeat / MaxNotes
Organophosphate or nerve agent poisoning (hospital)
2 g IV infusion over 15–30 min (do not bolus), diluted in 100 mL normal saline
Preferred: follow the load with a 1 g/hr infusion (AHA 2025 Table 4); the label says a load plus continuous infusion may keep levels therapeutic longer. Label alternative: repeat 1–2 g after about 1 hr if weakness persists, then every 10–12 hr. Titrate to muscle strength with toxicology
AHA 2025 Part 10 Table 4 (COR 2a, LOE A, recommendation 7). Differs from FDA label: 1–2 g load, second dose after about 1 hr if weakness persists, every 10–12 hr; no fixed adult infusion rate. Give after atropine has started working; never delay atropine for it. Pulmonary edema or fluid restriction: give the dose as 50 mg/mL by slow IV push no faster than 200 mg/min, so 1 g over at least 5 min and 2 g over at least 10 min
Organophosphate poisoning, weight-based load (WHO regimen)
30 mg/kg IV over 20 min, then 8 mg/kg/hr infusion
Continue until clinical recovery; adults commonly 2 g, then 500 mg/hr
WHO-recommended regimen (at least 30 mg/kg, then 8 mg/kg/hr), as described by the 2009 placebo-controlled trial and the 2026 umbrella review (References). That trial of the adult form (2 g over 20 min, then 500 mg/hr) found no survival benefit. Dosing weight not specified. See Continuous Infusion below
Nerve agent or insecticide, field autoinjector (adults and >41 kg)
600 mg IM per device (DuoDote, ATNAA or pralidoxime autoinjector), mid-lateral thigh
Mild (2 or more mild symptoms): 1 device; wait 10–15 min. If any severe symptom appears, give 2 more at once. Severe or unconscious: 3 in rapid succession. Max 3 devices (1,800 mg pralidoxime, 6.3 mg atropine), then definitive medical care; the DuoDote label gives no repeat course
DuoDote label (2.2, 3), which defines mild (1) and severe (3) only. If no severe symptom appears within 10–15 min, give no more. Continue IV atropine under medical direction
IM from the vial (no IV access)
600 mg IM (2 mL of the 300 mg/mL solution)
Mild: repeat every 15 min if symptoms persist, up to 3 doses. Severe: 3 doses in rapid succession. Max 1,800 mg per course; if symptoms persist, the series may be repeated about 1 hr after the last injection (Protopam label)
Protopam label. Subcut is also labeled when IV is not feasible
Overdose of anticholinesterase drugs (neostigmine, pyridostigmine, ambenonium)
1–2 g IV, then 250 mg IV every 5 min
No labeled max: titrate to strength with toxicology
Protopam label. May precipitate myasthenic crisis; have ventilatory support ready

Pediatric Dosing

IndicationDose (per kg) & RouteMax Single / Max TotalNotes
Organophosphate or nerve agent poisoning, IV (up to 40 kg or 14 years)
20–50 mg/kg IV over 15–30 min, then 10–20 mg/kg/hr infusion
Max 2 g per load. Intermittent option: repeat 20–50 mg/kg after about 1 hr, then every 10–12 hr
AHA 2025 Part 10 Table 4 and the Protopam label; AHA 2025 rec 8 rates pralidoxime reasonable in children (Class 2a, LOE B-R), extrapolated from adult data. Over 40 kg or 14 years: adult dosing. Dilute to 10–20 mg/mL; 50 mg/mL slow push only for pulmonary edema or fluid restriction, over at least 5 min and no faster than 200 mg/min (2 g over at least 10 min)
IM, under 40 kg
15 mg/kg IM per injection (300 mg/mL), anterolateral thigh
Mild: repeat at 15 min if mild symptoms persist (up to 3 injections). Severe: 3 in rapid succession. Max 45 mg/kg per three-injection course; a course can repeat about 1 hr after the last injection
Protopam label (updated April 1, 2026), from the vial reconstituted to about 300 mg/mL. 40 kg or more: adult 600 mg per injection
Combination autoinjector (DuoDote)
Over 41 kg: adult dosing (1 device if mild, 3 if severe)
41 kg or less: not established in children
House rule: no DuoDote or ATNAA at 41 kg or less. A 600 mg device exceeds the labeled 15 mg/kg IM dose in any child under 40 kg; use the weight-band AtroPen (see atropine) plus IM pralidoxime from the vial
Overdose of anticholinesterase drugs
Not established in children
Not routinely used (consult toxicology)
Call the poison center (1-800-222-1222)

Three weight cut-offs: Know which one you're applying. 14 years or 40 kg is the pediatric definition (NASEMSO v3.0, p. 13). The Protopam IM table splits at 40 kg: under 40 kg gets 15 mg/kg per injection, and 40 kg or more gets the adult 600 mg. The DuoDote and ATNAA label sets its line at 41 kg: safety and effectiveness are not established at 41 kg or less (DuoDote label, section 8.4).

Weight-based dose checks: pediatric weight-based dosing and Broselow tape.

Continuous Infusion

SettingExample ConcentrationStartTitrateUsual Range / Max
Adult, after the loading dose (fixed)
10–20 mg/mL in normal saline (example, institution-specific)
1 g/hr (not weight-based; AHA 2025 Table 4)
Fixed 1 g/hr. For persistent or returning weakness, reassess atropine and discuss further oxime dosing with toxicology. Reduce in renal impairment (label requires it; no regimen given)
1 g/hr (AHA 2025 Table 4); the label gives no adult rate
Adult, WHO regimen (weight-based)
10–20 mg/mL in normal saline (example, institution-specific)
8 mg/kg/hr after 30 mg/kg load
Continue until clinical recovery
8 mg/kg/hr; no fixed max
Pediatric (weight-based)
10–20 mg/mL in normal saline (example, institution-specific)
10–20 mg/kg/hr after 20–50 mg/kg load
Titrate to strength and respiratory effort with toxicology
10–20 mg/kg/hr. Maximum pediatric dose should not exceed adult dose (AHA 2025 Table 4 footnote); over 40 kg use adult dosing

The label permits intermittent doses every 10–12 hr. It adds that a loading dose followed by continuous infusion may hold levels in range longer than short intermittent infusions (label). Adult maintenance is 1 g/hr in AHA 2025 Table 4, and the label names no adult rate. Two high-dose versus low-dose RCTs are cited by AHA 2025, and both favored the high-dose arm (see Table 4 for dosing).

Preparation & Administration

  • IV dilution: reconstitute each 1 g vial with 20 mL sterile water for injection (50 mg/mL), then dilute in normal saline to 10–20 mg/mL (1 g or 2 g in 100 mL).
  • Rate: load over 15–30 min, and never faster than 200 mg/min on intermittent infusion. Go fast and you can get laryngospasm, muscle rigidity, tachycardia and cardiac arrest.
  • Undiluted push: 50 mg/mL, and only for pulmonary edema, fluid restriction or when an infusion isn't practical. Push no faster than 200 mg/min: 1 g over at least 5 min, 2 g over at least 10 min. The label states the 200 mg/min limit for intermittent infusion. Its push example (1 g in 20 mL over 5 min or longer) runs at that same rate.
  • IM from the vial: add 3.3 mL sterile water to a 1 g vial (about 300 mg/mL); 600 mg is 2 mL. Single-dose vial: discard the remainder.
  • Autoinjector technique: mid-lateral thigh, through clothing with pockets emptied, at 90 degrees; hold about 10 seconds. Bunch up a thin thigh. Bend the needle back and leave used devices with the patient so the next provider can count them.
  • Timing: start as early as possible, before the enzyme ages. Little is gained more than 36 hr after exposure ends. Ingested poison keeps absorbing, though, so re-dose every 3–8 hr while signs recur.
Dosing Notes: The Protopam label carries no boxed warning. Kidney and liver considerations are under Special Populations.

Contraindications & Precautions

Contraindications

  • None absolute in life-threatening organophosphate or nerve agent poisoning
  • Known hypersensitivity to pralidoxime (relative)

Precautions

  • Carbamate poisoning: known carbamate-only exposure gets atropine and supportive care, not routine pralidoxime. Unknown agent, or a possible organophosphate? Give it. AHA 2025 finds the data insufficient to recommend for or against oximes in carbamate poisoning. It also says not to withhold one when the class is unknown. Differs from FDA label: the Protopam label says pralidoxime is not indicated for carbamate pesticides, because it may increase carbaryl toxicity.
  • Myasthenia gravis: reversing the therapeutic cholinesterase inhibition may precipitate myasthenic crisis.
  • Rapid IV administration: a fast push can transiently worsen cholinergic signs: tachycardia, laryngospasm, rigidity, paralysis and cardiac arrest.
  • Renal impairment: it leaves the body through the kidneys, so levels rise and doses must come down.
  • Cardiovascular disease (DuoDote): atropine can drive tachyarrhythmias and ischemia.
  • Other atropine cautions (DuoDote): watch for acute glaucoma risk, bladder outflow obstruction, partial pyloric stenosis and chronic lung disease (viscid secretions: monitor respiratory status). See atropine. None of these outweighs treating life-threatening poisoning.

Hold / Reassess If

  • Laryngospasm, apnea, muscle rigidity or a new arrhythmia during IV loading: stop the infusion, support the airway, restart more slowly
  • Marked hypertension or tachycardia during the infusion: slow the rate and reassess atropine dosing
  • Weakness worsening in a patient on myasthenia therapy: stop and prepare to ventilate
  • Rising creatinine or falling urine output on a prolonged infusion: reduce the dose with toxicology
Atropine comes first: Atropine handles the bronchorrhea, bronchospasm and bradycardia that kill early. Pralidoxime is the adjunct that restores muscle strength. Never delay atropine to prepare or give pralidoxime.

Adverse Effects & Toxicity

Common

  • Blurred vision, diplopia and impaired accommodation
  • Dizziness, headache, drowsiness and nausea
  • Tachycardia and raised blood pressure: one DuoDote raised SBP by about 16 mmHg at 15 min, near baseline by 4 hr
  • Hyperventilation and muscular weakness (in unpoisoned volunteers)
  • Mild to moderate pain 40–60 min after IM injection
  • Transient rises in AST/ALT and creatine kinase

Serious / Life-Threatening

EffectRecognitionManagement
Laryngospasm, rigidity or cardiac arrest with rapid IV
Stridor, chest-wall rigidity, apnea or arrest during a push or fast infusion
Stop; airway and ventilation, ACLS; resume as a slow infusion
Myasthenic crisis
Worsening weakness and respiratory effort in a patient on cholinesterase inhibitors
Ventilatory support; toxicology and neurology input
Earlier atropine toxicity
Flushing, mydriasis, tachycardia, dry mouth sooner than expected, especially after large atropine doses (Protopam label, Drug Interactions)
Reassess the atropine rate against a clear chest, HR and SBP
Excitement or manic behavior on waking
Agitation as consciousness returns (also seen without pralidoxime)
Benzodiazepine (diazepam or midazolam); rule out hypoxia and atropine delirium

Overdose & Toxicity Management

  • Signs: dizziness, blurred vision, diplopia, headache, impaired accommodation, nausea and slight tachycardia. Transient hypertension may last several hours. These are hard to tell apart from the poisoning itself.
  • Management: no antidote; stop or slow the infusion and give supportive care.
  • Accidental injection of DuoDote in an unpoisoned person: the atropine dose impairs vision, walking and thinking. Avoid heat and exertion and seek medical review.

Monitoring
ParameterWhen / How OftenTarget / Act If
Clinical: airway and ventilation
Continuous
Secretions or wheeze: more atropine. Weakness, falling tidal volume or poor cough: intubate early (AHA Class 1) with a non-depolarizing paralytic
Clinical: muscle strength
Before each dose and serially during the infusion (neck flexion, grip, respiratory effort)
Weakness persisting about 1 hr after the load, if no infusion is running: start 1 g/hr (adult, AHA 2025 Table 4); label alternative is a second 1–2 g dose
Clinical: atropinization targets
Every 5 min while titrating atropine
Clear chest, HR >80/min, SBP >80 mmHg; pralidoxime can bring on atropine effects sooner
Clinical: HR, BP and ECG
Continuous during IV loading and the first hours
Tachycardia or hypertension: slow the infusion. Laryngospasm or arrest: stop
Clinical: relapse after improvement
Observe at least 48–72 hr
Recurrent cholinergic signs from ongoing gut absorption: give more atropine and re-dose pralidoxime (label: every 3–8 hr while signs recur). Neck-flexor, proximal or respiratory weakness later in the course (intermediate syndrome): support ventilation early; oximes have not been shown to prevent it. The 2020 Kharel meta-analysis, as tabulated in the 2026 Chauhan review, found more intermediate syndrome with pralidoxime (RR 1.63, very low certainty)
Laboratory: RBC and plasma cholinesterase
Baseline and serially if available
Never wait for results. RBC cholinesterase <50% of normal supports organophosphate poisoning; a normal value does not exclude it
Laboratory: renal function
Baseline and daily during infusion
Rising creatinine or falling urine output: reduce the dose
Laboratory: liver enzymes and CK
If therapy is prolonged
AST/ALT rises returned to normal in about 2 weeks in volunteers; CK rises are transient (Protopam label)

Interactions & Compatibility

Clinically Significant Interactions

Drug / ClassEffectWhat To Do
Atropine
Signs of atropinization appear earlier, especially after large atropine doses and delayed pralidoxime
Keep titrating atropine to a clear chest, HR and SBP; watch for delirium and hyperthermia
Succinylcholine and mivacurium
Paralysis prolonged by hours in organophosphate or carbamate poisoning (AHA 2025 Part 10, rec 9). Label: prolonged paralysis reported when succinylcholine is given with anticholinesterase-active drugs; use with caution
Not recommended by AHA 2025 (3: No Benefit): use rocuronium or vecuronium
Cholinesterase inhibitors for myasthenia (neostigmine, pyridostigmine)
Pralidoxime opposes them and may precipitate myasthenic crisis
In a myasthenic patient with organophosphate poisoning or anticholinesterase overdose, give with great caution and have ventilatory support ready; watch for myasthenic crisis
Barbiturates
Potentiated by anticholinesterases
Prefer a benzodiazepine for seizures and agitation
Morphine, theophylline, aminophylline, reserpine, phenothiazines
Labeled to be avoided in organophosphate poisoning
Choose alternatives

IV Compatibility

  • Reconstitute with sterile water for injection; dilute in normal saline
  • The label does not address Y-site compatibility
  • Verify with an institutional compatibility resource.

Special Populations
  • Pediatrics: there are no adequate trials. Dosing is extrapolated from adult pharmacokinetics and pediatric experience. AHA 2025 rates pralidoxime reasonable for children with life-threatening organophosphate poisoning (Class 2a, LOE B-R), extrapolated mainly from adult trials. Rapid IV injection has been followed by laryngospasm, cardiac arrest, tachycardia and rigidity or paralysis. Fasciculations, apnea and seizures have also been reported. Infants may be drowsy and floppy rather than twitching. Tearing, runny nose, drooling and incontinence are less reliable signs. Doses: Pediatric Dosing table.
  • Pregnancy: no human or animal reproduction data exist for pralidoxime. Atropine crosses the placenta. Life-threatening poisoning threatens both mother and fetus, so treat with standard doses.
  • Lactation: it is unknown whether pralidoxime enters breast milk. Atropine does. Use it short-term in an emergency, and weigh breastfeeding against the mother's condition.
  • Older Adults: no differences have been identified. Start at the low end of the dose range, because reduced renal function is more common. Older adults are more sensitive to DuoDote's atropine.
  • Renal Impairment: renal tubular secretion clears it, so levels rise as function falls. The label requires a reduced dose but gives no regimen. Severe impairment may need less frequent doses after the first. Adjust with toxicology.
  • Hepatic Impairment: in severe impairment, doses after the first may be needed less often (DuoDote label).
  • Obesity / Dosing Weight: no dosing-weight guidance is established. Adult regimens are commonly fixed: 2 g load, then 1 g/hr (AHA 2025 Table 4).
  • Myasthenia Gravis: it may precipitate myasthenic crisis. Use it for organophosphate poisoning only with ventilatory support ready.

Field & Transport Considerations
  • Scope: who may carry or give autoinjector antidotes and IV pralidoxime varies by state and agency. Confirm your credentials and medical-direction approval before use.
  • Storage & Stability: vials store at 20–25°C (68–77°F), and DuoDote at 25°C (77°F). Both tolerate excursions of 15–30°C (59–86°F). Keep autoinjectors from freezing and in their light-protective pouch.
  • Carried Concentration: each DuoDote holds 600 mg pralidoxime and 2.1 mg atropine. Three devices give you 1,800 mg pralidoxime, but only 6.3 mg atropine. Severe poisoning needs IV atropine on top.
  • Three per Person: keep 3 autoinjectors for every person at risk, providers included (DuoDote label).
  • Mass Casualty and CHEMPACK: Strategic National Stockpile containers, mostly in hospitals and fire stations, hold DuoDote and ATNAA, pralidoxime autoinjectors and 1 g vials, atropine, diazepam and midazolam. EMS containers treat up to 454 people. Hospital containers treat up to 1,000. State and local officials open them without a federal request.
  • Scene Safety: protective equipment comes first. Remove clothing and wash skin with soap and water. Unprotected staff have been poisoned through contact with patients.
  • Altitude / Environment: the atropine in DuoDote blocks sweating. Heat, exertion and protective suits raise the risk of heat injury.
  • Handoff Essentials: suspected agent and exposure time; number of autoinjectors and times (show the used devices); IV pralidoxime total and current rate; total atropine; last strength and chest examination.

Clinical Pearls
Atropine dries, pralidoxime strengthens: Atropine handles the muscarinic side: secretions, bronchospasm, bradycardia. None of that reaches the neuromuscular junction. Fasciculations, weakness and paralysis are nicotinic, and they need pralidoxime and ventilation. NREMT and FP-C test this split as a discriminator.
Beat the aging clock: Once the poison-enzyme bond ages, no oxime can break it. Soman ages in about 2 minutes. VR (Russian VX)-inhibited enzyme ages with a half-time of almost 140 hours. Tabun ages rapidly (AHA 2025 Part 10). Dimethyl insecticides such as malathion and dimethoate work differently. Their inhibited enzyme reactivates on its own, with a half-life of about 0.7 hours for malaoxon. So spontaneous recovery contributes, and the oxime effect is less certain (the 2020 Worek review). Give it early, alongside atropine.
Never push it fast: Push it fast and you can get laryngospasm, rigidity and cardiac arrest. Load by infusion over 15–30 min. Keep the airway ready during the load.
The carbamate controversy: Carbamates bind cholinesterase reversibly and never age, which is why an oxime adds little. Known carbamate-only exposure is managed with atropine and supportive care. The FDA label says pralidoxime is not indicated for carbamate pesticides, such as carbaryl. AHA 2025 calls the data insufficient and advises against withholding it when the agent is unknown.
Guideline versus trials: Placebo-controlled trials and meta-analyses show no clear mortality benefit. One 2020 meta-analysis found a non-significant mortality risk ratio of 1.53, and more intermediate syndrome (RR 1.63). AHA 2025 still rates pralidoxime reasonable (Class 2a). Its placebo-controlled RCTs were heterogeneous and used lower doses. Two high-dose versus low-dose RCTs favored the high-dose groups: survival, pneumonia, lower atropine use. Late treatment, aged enzyme and massive ingestions also limit effect.
Watch for the second wave: Ingested insecticide goes on being absorbed, so cholinergic signs can come back. That means more atropine and pralidoxime. Weakness of the neck flexors and breathing muscles can also turn up later in the course. That is intermediate syndrome, and it needs early ventilatory support. Oximes have not been shown to prevent it. Observe for at least 48–72 hours before discharge.

Pharmacology

Mechanism of Action

Drawn from the Protopam label (clinical pharmacology) and AHA 2025 Part 10 (21.12).

  • Organophosphates phosphorylate acetylcholinesterase. Acetylcholine then piles up at muscarinic, nicotinic and central synapses.
  • Pralidoxime, a quaternary oxime, strips the phosphoryl group off and reactivates the enzyme, mainly outside the CNS. Its key effect is relieving respiratory muscle paralysis.
  • Aging, the dealkylation of the bound poison, makes the enzyme permanently resistant. Pralidoxime slows aging and directly detoxifies some organophosphates.
  • It gets into the CNS poorly, so it does not reverse central apnea or seizures. Atropine and benzodiazepines remain essential.
  • Only a minor effect on muscarinic signs.

Pharmacokinetics

RouteOnsetPeakDuration
IM (600 mg)
Reaches 4 mcg/mL (an animal-derived minimum therapeutic level) in about 16 min (label)
About 30 min (Tmax 28 ± 15 min after DuoDote; 33–34 min after 1 g IM in the Protopam label)
Short-acting: repeat or infuse
IV (1 g)
Expected during the load (no published onset)
Expected at the end of the infusion (not reported)
Below 4 mcg/mL in about 1.5 hr (label simulation)
  • Half-life: apparent half-life 74–77 min; about 3 hr after 1 g IM; 2.4–5.3 hr after a continuous infusion stops (Protopam label).
  • Metabolism: partly hepatic, to a metabolite excreted in urine.
  • Elimination: renal tubular secretion does the work, with 72–94% leaving unchanged (DuoDote label). In poisoned patients, renal clearance is roughly halved (Protopam label: 7.2 vs 3.6 mL/min/kg).
  • Protein binding / Vd: not protein bound; Vd 0.6–2.7 L/kg (extracellular water).

Names & Classification
Generic Name
Pralidoxime chloride (2-PAM chloride)
Brand Names
Protopam Chloride (vial); DuoDote and ATNAA (with atropine); pralidoxime chloride autoinjector (Mark I kit)
Pharmacologic Class
Oxime cholinesterase reactivator
Therapeutic Class
Antidote for organophosphate insecticide and nerve agent poisoning
Controlled Substance
Not controlled

Related

References
  1. Baxter Healthcare Corporation. (2026). Protopam Chloride (pralidoxime chloride) for injection [prescribing information]. DailyMed, National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2741d8fd-51c2-46be-880b-99f2b20a6137
  2. Meridian Medical Technologies. (2022). DuoDote (atropine and pralidoxime chloride injection) auto-injector, for intramuscular use [prescribing information]. DailyMed, National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=241f42a0-1a33-40e8-8221-201767d999e5
  3. Cao, D., Arens, A. M., Chow, S. L., Easter, S. R., Hoffman, R. S., Lagina, A. T., et al. (2025). Part 10: Adult and pediatric special circumstances of resuscitation: 2025 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation, 152(16 Suppl 2), S578–S672. https://doi.org/10.1161/CIR.0000000000001380
  4. Chauhan, V., Goyal, D., Thakur, S., Galwankar, S., & Peredy, T. R. (2026). Therapeutic interventions in organophosphate poisoning: an umbrella review of systematic reviews. Western Journal of Emergency Medicine, 27(3), 819–830. https://doi.org/10.5811/westjem.50823
  5. Worek, F., Thiermann, H., & Wille, T. (2020). Organophosphorus compounds and oximes: a critical review. Archives of Toxicology, 94(7), 2275–2292. https://doi.org/10.1007/s00204-020-02797-0
  6. Administration for Strategic Preparedness and Response. (2026). CHEMPACK. Strategic National Stockpile, US Department of Health and Human Services. https://www.aspr.gov/SNS/Pages/CHEMPACK.aspx
  7. Eddleston, M., Eyer, P., Worek, F., et al. (2009). Pralidoxime in acute organophosphorus insecticide poisoning: a randomised controlled trial. PLoS Medicine, 6(6), e1000104. https://doi.org/10.1371/journal.pmed.1000104
  8. Kharel, H., Pokhrel, N. B., Ghimire, R., & Kharel, Z. (2020). The efficacy of pralidoxime in the treatment of organophosphate poisoning in humans: a systematic review and meta-analysis of randomized trials. Cureus, 12(3), e7174. https://doi.org/10.7759/cureus.7174
  9. National Association of State EMS Officials. (2022). National Model EMS Clinical Guidelines, Version 3.0. NASEMSO. https://nasemso.org/docs.ashx?id=1444322

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