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Medically reviewed by Last updated on Jul 22, 2019.


(fye zoe STIG meen)

Index Terms

  • Eserine Salicylate
  • Physostigmine Salicylate
  • Physostigmine Sulfate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection, as salicylate:

Generic: 1 mg/mL (2 mL)

Pharmacologic Category

  • Acetylcholinesterase Inhibitor
  • Antidote


Physostigmine is a carbamate which inhibits the enzyme acetylcholinesterase and prolongs the central and peripheral effects of acetylcholine


IM: Readily absorbed


Widely distributed throughout the body; crosses blood-brain barrier readily and reverses both central and peripheral anticholinergic effects


Via hydrolysis by cholinesterases

Onset of Action

Within 3 to 8 minutes

Duration of Action

45 to 60 minutes

Half-Life Elimination

1 to 2 hours

Use: Labeled Indications

Reversal of central nervous system anticholinergic syndrome

Note: Due to the risk to benefit ratio, physostigmine should only be used to reverse toxic, life-threatening delirium caused by pure anticholinergic agents (ie, atropine, benztropine, scopolamine, dimenhydrinate, diphenhydramine, Atropa belladonna [deadly nightshade], jimson weed [Datura spp]). Consultation with a clinical toxicologist or poison control center is recommended in patients who may require physostigmine administration. When indicated and used properly by a clinical toxicologist, physostigmine is safe and effective (Watkins 2015).


Gastrointestinal or genitourinary obstruction; asthma; gangrene; diabetes; cardiovascular disease; any vagotonic state; coadministration of choline esters and depolarizing neuromuscular-blocking agents (eg, succinylcholine)

Note: Physostigmine should not be used in the absence of toxicity from an anticholinergic agent (Howland 2015).

Dosing: Adult

Reversal of toxic anticholinergic effects: Note: When administering by IV injection, administer no faster than 1 mg/minute to prevent bradycardia, respiratory distress, and seizures from too rapid administration.

IM, IV: Initial: 0.5 to 2 mg; may repeat every 10 to 30 minutes until response occurs. Subsequent doses may be required to manage life-threatening anticholinergic effects (Krenzelok 2010).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Reversal of toxic anticholinergic effects: Note: Reserve for life-threatening situations only: Infants, Children, and Adolescents: IM, IV: Initial: 0.02 mg/kg; may repeat every 5 to 10 minutes until response occurs; maximum total dose: 2 mg/dose. Note: For IV, slow administration (≤0.5 mg/minute for pediatric patients) is required to prevent bradycardia, respiratory distress, and seizures. In one retrospective chart review of adult patients with likely anticholinergic toxicity (n=45), 69% of patients only required a single dose of physostigmine; in addition, even in patients who required multiple doses of physostigmine, further dosing beyond 6.5 hours (after the initial dose) was generally unnecessary (Rosenbaum 2010).


IV: Infuse no faster than 1 mg/minute. Too rapid administration can cause bradycardia, respiratory distress, and seizures. May also be administered IM (according to the manufacturer's labeling).


Store at 20°C to 25°C (68°F to 77°F).

Drug Interactions

Amifampridine: Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Amifampridine. Amifampridine side effects may also be increased. Amifampridine may enhance the therapeutic effect of Acetylcholinesterase Inhibitors. Acetylcholinesterase inhibitor side effects may also be increased. Monitor therapy

Anticholinergic Agents: Acetylcholinesterase Inhibitors may diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy

Benoxinate: Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Benoxinate. Specifically, the effects of benoxinate may be prolonged. Monitor therapy

Beta-Blockers: Acetylcholinesterase Inhibitors may enhance the bradycardic effect of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. Monitor therapy

Cholinergic Agonists: Acetylcholinesterase Inhibitors may enhance the adverse/toxic effect of Cholinergic Agonists. Monitor therapy

Corticosteroids (Systemic): May enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur. Monitor therapy

Dipyridamole: May diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy

Neuromuscular-Blocking Agents (Nondepolarizing): Acetylcholinesterase Inhibitors may diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Succinylcholine: Acetylcholinesterase Inhibitors may increase the serum concentration of Succinylcholine. Management: Consider alternatives to this combination due to a risk of prolonged neuromuscular blockade. Consider therapy modification

Test Interactions

Increased aminotransferase [ALT/AST] (S), increased amylase (S)

Adverse Reactions

Frequency not defined.

Cardiovascular: Asystole, bradycardia, palpitations

Central nervous system: Hallucination, nervousness, restlessness, seizure, twitching

Dermatologic: Diaphoresis

Gastrointestinal: Diarrhea, frequent bowel movements, nausea, salivation, stomach pain, vomiting

Genitourinary: Urinary frequency

Hypersensitivity: Hypersensitivity reaction

Ophthalmic: Lacrimation, miosis

Respiratory: Bronchospasm, dyspnea, pulmonary edema, respiratory distress, respiratory paralysis


Concerns related to adverse effects:

• Arrhythmias: Patient must have a normal QRS interval, as measured by ECG, in order to receive; use caution in poisoning with agents known to prolong intraventricular conduction (Howland 2011).

• Cholinergic effects: Discontinue if symptoms of excessive cholinergic activity occur (eg, salivation, urinary incontinence, defecation, vomiting); overdosage may result in cholinergic crisis, which must be distinguished from myasthenic crisis. If excessive diaphoresis or nausea occurs, reduce subsequent doses.

• Hypersensitivity/overdose reactions: Due to the possibility of hypersensitivity or overdose/cholinergic crisis, atropine should be readily available.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.

• Sodium metabisulfite: Products may contain sodium metabisulfite which may cause allergic reactions in some individuals.

Other warnings/precautions:

• IV administration: Administer no faster than 1 mg/minute in adults or 0.5 mg/minute in children to prevent bradycardia, respiratory distress, and seizures from too rapid administration. Although the use of continuous infusions of physostigmine have been described in the literature (Eyer 2008; Hail 2013; Phillips 2015), experts do not recommend the routine use of continuous infusions. It is preferable to titrate physostigmine to patient needs through the use of intermittent administration; intermittent administration will minimize the risk of cholinergic toxicity, which can be associated with considerable morbidity.

• Tricyclic antidepressant (TCA) poisoning: Asystole and seizures have been reported when physostigmine was administered to TCA poisoned patients. Physostigmine is not recommended in patients with known or suspected TCA intoxication.

Monitoring Parameters

ECG, vital signs; consult individual institutional policies and procedures

Pregnancy Considerations

In general, medications used as antidotes should take into consideration the health and prognosis of the mother; antidotes should be administered to pregnant women if there is a clear indication for use and should not be withheld because of fears of teratogenicity (Bailey, 2003).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Have patient report immediately to prescriber severe nausea, severe vomiting, severe diarrhea, polyuria, seizures, increased saliva, sweating a lot, or bradycardia (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.