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Generic name: physostigmine systemic

Brand names: Antilirium, Anticholium

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)


Mechanism of Action

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: Consultation with a clinical toxicologist or poison control center may be prudent if physostigmine administration is being considered. Physostigmine is most efficacious for delirium resulting from drugs with predominant anticholinergic properties (eg, atropine, benztropine, scopolamine, dimenhydrinate, diphenhydramine, Atropa belladonna [deadly nightshade], jimson weed [Datura spp]), but may also be beneficial for other medications with anticholinergic effects (eg, atypical antipsychotics, cyclobenzaprine, hydroxyzine [Cole 2012; Grenga 2018; Rasimas 2014; Weizberg 2006]). Risk:benefit should always be considered. When indicated and used properly by a clinical toxicologist, physostigmine is safe and effective (Arens 2018; 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 2019).

Dosage and Administration

Dosing: Adult

Reversal of toxic anticholinergic effects: Note: When administering by IV injection, administer no more rapidly than 1 mg/minute to prevent bradycardia, respiratory distress, and seizures from too rapid administration. Slower administration (ie, over no less than 5 minutes) may be preferable (Howland 2019).

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; maximum dose: 0.5 mg/dose (Howland 2019); 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 more rapidly than 1 mg/minute. Too rapid administration may cause bradycardia, respiratory distress, and seizures. Slower administration (ie, over no less than 5 minutes) may be preferable (Howland 2019). 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 2019).
  • Cholinergic effects: Symptoms of excessive cholinergic activity may occur (eg, salivation, urinary incontinence, defecation, vomiting). If excessive diaphoresis or nausea occurs, reduce subsequent doses. Atropine should be available to reverse cholinergic symptoms, if necessary.
  • Hypersensitivity reactions: Hypersensitivity reactions may occur in patients with allergy to cholinesterase inhibitors or salicylates.
  • Seizure: Use with caution in patients with a known seizure disorder or coingestion of epileptogenic drugs. Risk of seizure activity increases with too rapid administration.

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 more rapidly than 1 mg/minute in adults or 0.5 mg/minute in children to prevent bradycardia, respiratory distress, and seizures from too rapid administration. Administration at an even slower rate (ie, over no less than 5 minutes) may be preferable (Howland 2019). Although the use of a continuous infusion of physostigmine has been described in the literature (Eyer 2008; Hail 2013; Phillips 2015), the routine use of a continuous infusion is not recommended. A continuous infusion may be considered for patients with profound anticholinergic effects who require frequent doses of physostigmine. However, it is preferable to titrate physostigmine to patient needs through the use of intermittent administration.
  • 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, passing a lot of urine, seizures, increased saliva, sweating a lot, or slow heartbeat (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.

Source: Wolters Kluwer Health. Last updated January 31, 2020.