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Antidotes & Toxicology Pregnancy: Animal reproduction studies have not been conducted with pralidoxime chloride. It is also not known whether pralidoxime chloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Pralidoxime chloride should be given to a pregnant woman only if clearly needed. Nursing mothers: it is not known whether this drug is excreted in human milk; caution should be exercised when pralidoxime chloride is administered to a nursing woman.

Pralidoxime

Brand names: P2S, Pralidoxime Mesylate

Pralidoxime is a cholinesterase reactivator used, alongside atropine, in the treatment of poisoning by organophosphate insecticides and nerve agents.

Adult dose

Dose: Organophosphate (anticholinesterase pesticide / nerve agent) poisoning, adults, intravenous: initial dose 1000 to 2000 mg pralidoxime chloride, preferably as an infusion in 100 mL normal saline over 15 to 30 minutes
Route: Intravenous infusion (preferred, slowly); if intravenous administration is not feasible, intramuscular or subcutaneous injection
Frequency: A second dose of 1000 to 2000 mg may be indicated after about one hour if muscle weakness has not been relieved; additional doses may be given every 10-12 hours if muscle weakness persists
The same label also covers control of overdosage by anticholinesterase drugs used in myasthenia gravis. Treatment should include general supportive care, atropinization and decontamination in addition to pralidoxime; 'After the effects of atropine become apparent, PROTOPAM Chloride may be administered.' Treatment is most effective if initiated immediately after poisoning; 'Generally, little is accomplished if PROTOPAM Chloride is given more than 36 hours after termination of exposure to the poison.' Keep the patient under observation for at least 48 to 72 hours. ADULT INTRAVENOUS (label): 'Inject an initial dose of 1000 to 2000 mg of PROTOPAM Chloride, preferably as an infusion in 100 mL of normal saline, over a 15- to 30-minute period. If this is not practical or if pulmonary edema is present, the dose should be given slowly (over not less than five minutes) by intravenous injection, as a 50 mg/mL solution in water (e.g., 1000 mg in 20 mL). A second dose of 1000 to 2000 mg may be indicated after about one hour if muscle weakness has not been relieved. Additional doses may be given every 10-12 hours if muscle weakness persists.' Where the poison has been ingested, continuing absorption can cause fatal relapses: additional doses may be needed every three to eight hours, titrated 'as long as signs of poisoning recur'. RATE: the intermittent infusion rate should not exceed 200 mg/minute; infusing too rapidly may cause temporary worsening of cholinergic manifestations (tachycardia, cardiac arrest, laryngospasm, muscle rigidity or paralysis). If intravenous administration is not feasible, intramuscular or subcutaneous injection should be used. ADULT INTRAMUSCULAR (label, approx. 300 mg/mL solution): mild symptoms - 600 mg (2 mL), wait 15 minutes, a second 600 mg if mild symptoms persist, and after a further 15 minutes a third 600 mg, total cumulative dose 1800 mg; if severe symptoms develop at any time, give two additional 600 mg doses in rapid succession (total 1800 mg); severe symptoms - three 600 mg intramuscular doses in rapid succession (total 1800 mg); if symptoms persist after the complete 1800 mg regimen, the series may be repeated beginning approximately 1 hour after the last injection. ANTICHOLINESTERASE OVERDOSAGE (myasthenia gravis drugs - neostigmine, pyridostigmine, ambenonium): 'may be given in a dosage of 1000 to 2000 mg intravenously followed by increments of 250 mg every five minutes.' PREPARATION (label): reconstitute a 1000 mg vial with 20 mL Sterile Water for Injection (50 mg/mL), then dilute with Normal Saline to 10 to 20 mg/mL (e.g. 1000 mg in 100 mL or 2000 mg in 100 mL) for infusion; for fluid-restricted patients or rapid administration (over at least 5 min) a maximum concentration of 50 mg/mL may be used. Not effective for poisoning due to phosphorus, inorganic phosphates, or organophosphates without anticholinesterase activity; not indicated for carbamate pesticide poisoning (may increase toxicity of carbaryl). The label prints no daily maximum dose, so maxDose is left empty (the 200 mg/minute figure is a maximum infusion RATE, not a dose ceiling). SALT/PRODUCT SCOPE: this page's brand names include 'P2S' and 'Pralidoxime Mesylate', but the only open label retrieved is for pralidoxime CHLORIDE (Protopam Chloride); every figure above is a pralidoxime chloride dose and the label does not cover any other salt - do not apply these mg figures to a mesylate product without checking its own labelling. No UK SPC for pralidoxime is listed on eMC — this dose is from US prescribing information (Protopam Chloride) and must be verified against UK practice.

Paediatric dose

Dose: Organophosphate poisoning, patients 16 years and under (label), intravenous: loading dose of 20-50 mg/kg (not to exceed 2000 mg/dose) over 15-30 minutes followed by a continuous infusion of 10-20 mg/kg/hour; or intermittent infusion of an initial 20-50 mg/kg (not to exceed 2000 mg/dose) over 15-30 minutes. Intramuscular (anterolateral thigh): children under 40 kg - 15 mg/kg per injection, given as three injections (total 45 mg/kg per three-injection course); children of 40 kg or more - use the adult dosing recommendations (600 mg per injection, 1800 mg per three-injection course). The specific dose depends on the severity of symptoms.
Route: Intravenous infusion (loading dose then continuous, or intermittent); or intramuscular into the anterolateral thigh
Frequency: IV intermittent: a second dose of 20-50 mg/kg may be indicated after about one hour if muscle weakness has not been relieved; repeat dosing is permissible every 10-12 hours as needed. IM: mild symptoms - one injection, repeated at 15 minutes and again after a further 15 minutes if mild symptoms persist; severe symptoms - three injections in rapid succession; the series may be repeated beginning approximately 1 hour after the last injection (additional courses may begin one hour after the last injection).
Max: IV: 2000 mg/dose (label: 'not to exceed 2000 mg/dose'). IM: total per three-injection course not to exceed 45 mg/kg for children under 40 kg.
US label 'Pediatric Dosing (for patients 16 years and under)'. If intravenous infusion is not practical or pulmonary edema is present, the 20-50 mg/kg dose should be given slowly (over not less than five minutes) by intravenous injection as a 50 mg/mL solution in water; additional doses every 10-12 hours if muscle weakness persists. The label states there are no adequate and well-controlled clinical trials establishing effectiveness in paediatric patients; efficacy has been extrapolated from adults and the IM regimen was derived by pharmacokinetic modelling. Infants and young children may become drowsy or unconscious with muscle floppiness rather than twitching. Clinician to verify against a children's formulary before use.

Dose adjustments

Renal

Because pralidoxime is excreted in the urine, a decrease in renal function will result in increased blood levels of the drug; the dosage of pralidoxime chloride should be reduced in the presence of renal insufficiency (the retrieved US label gives no numeric renal dose adjustment).

Hepatic

Not stated in the product information we used — check the full SPC.

Dose independently re-sourced from US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • No known absolute contraindications; relative contraindications include known hypersensitivity to the drug and other situations in which the risk of its use clearly outweighs possible benefit
  • Not effective in poisoning due to phosphorus, inorganic phosphates, or organophosphates not having anticholinesterase activity
  • Not indicated as an antidote for intoxication by carbamate-class pesticides - it may increase the toxicity of carbaryl
  • Use with great caution in organophosphate overdosage in patients with myasthenia gravis - it may precipitate a myasthenic crisis

Side effects

  • Mild to moderate pain at the injection site 40 to 60 minutes after intramuscular injection
  • In normal volunteers given parenterally: blurred vision, diplopia and impaired accommodation, dizziness, headache, drowsiness, nausea, tachycardia, increased systolic and diastolic blood pressure, hyperventilation and muscular weakness
  • Too-rapid intravenous administration: temporary worsening of cholinergic manifestations (tachycardia, cardiac arrest, laryngospasm, muscle rigidity or paralysis)
  • Elevations in SGOT and/or SGPT (observed in normal volunteers given 1200 mg or 1800 mg intramuscularly; returned to normal in about 2 weeks) and transient creatine phosphokinase elevations
  • Excitement and manic behaviour immediately following recovery of consciousness (also seen in organophosphate poisoning not treated with pralidoxime)
  • In patients it is very difficult to differentiate toxic effects of atropine or the organophosphate compounds from those of the drug

Interactions

  • Atropine - signs of atropinization (flushing, mydriasis, tachycardia, dryness of the mouth and nose) may occur earlier than expected, especially if the total atropine dose has been large and pralidoxime delayed
  • Morphine, theophylline, aminophylline, reserpine and phenothiazine-type tranquilizers should be avoided in patients with organophosphate poisoning
  • Barbiturates are potentiated by anticholinesterases - use cautiously in the treatment of convulsions
  • Succinylcholine - prolonged paralysis has been reported with drugs having anticholinesterase activity; use with caution

Monitoring

  • Observe the patient for at least 48 to 72 hours after organophosphate poisoning
  • Muscle weakness and respiratory depression (the principal indications for use) and recurrence of signs of poisoning
  • Red blood cell and plasma cholinesterase, and urinary paranitrophenol (parathion exposure), may help confirm the diagnosis and follow the course, but may be normal despite clinically significant poisoning - do not delay treatment for results
  • Maintain some degree of atropinization for at least 48 hours and until any depressed blood cholinesterase activity is reversed
  • Renal function - dosage should be reduced in renal insufficiency

Clinical monograph

How it works

It reactivates acetylcholinesterase by displacing the organophosphate from the enzyme, restoring acetylcholine breakdown, but only before irreversible 'ageing' of the enzyme-organophosphate bond occurs.

Prescribing in practice

  • It must be given as early as possible and always in addition to, not instead of, atropine, which remains the primary antidote for muscarinic effects.
  • Efficacy falls once the inhibited enzyme has aged, so it is most useful when started promptly after exposure.
  • Administer by slow intravenous infusion and follow UK poisons information advice on its use and continuation.

Monitoring

Monitor neuromuscular and respiratory function, atropinisation and, where available, cholinesterase activity to guide ongoing treatment.

Counselling the patient

  • Explain to the team that this drug reactivates the poisoned enzyme but works together with atropine.
  • Stress that it should be started as early as possible after organophosphate exposure.
  • Note that decontamination and airway support are essential parts of management.

Evidence & guidelines

Pralidoxime with atropine is the standard antidotal regimen for organophosphate and nerve-agent poisoning, with use guided by UK poisons information (TOXBASE).

Reference: NPIS Toxbase; WHO Guidelines for Organophosphate Poisoning; Lancet 2009; 374(9694):992-1000; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

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