Note: Consultation with a clinical toxicologist or poison control center is recommended prior to use.
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 ≥5 minutes) may be preferable. The duration of action of some anticholinergic agents may exceed the duration of action of physostigmine; therefore, monitor closely for recurrence of symptoms (Howland 2019).
IM, IV: Initial: 0.5 to 2 mg; may repeat every 10 to 30 minutes until response occurs. Generally, a single dose or a short duration of treatment (<6.5 hours) is sufficient (Rosenbaum 2010; manufacturer's labeling); longer durations of therapy may be required to manage life-threatening anticholinergic effects (Krenzelok 2010).
There are no dosage adjustments provided in the manufacturer’s labeling.
There are no dosage adjustments provided in the manufacturer’s labeling.
(For additional information see "Physostigmine: Pediatric drug information")
Reversal of toxic anticholinergic effects:
Note: Reserve for life-threatening situations only. Slow IV administration (≤0.5 mg/minute for pediatric patients) is required to prevent bradycardia, respiratory distress, and seizures. Slower administration (ie, over no less than 5 minutes) may be preferable (Howland 2019). The duration of action of some anticholinergic agents may exceed the duration of action of physostigmine; therefore, monitor closely for recurrence of symptoms (Howland 2019). Consultation with a clinical toxicologist or poison control center is recommended.
Infants, Children, and Adolescents: IM, IV: Initial: 0.02 mg/kg; maximum dose: 0.5 mg/dose; may repeat every 5 to 15 minutes until response occurs (AAP [Shenoi 2020]; Howland 2019); maximum total dose: 2 mg (total). Subsequent doses may be required to manage clinical relapse (Howland 2019). Based on adult experience, a short total duration of therapy (<6.5 hours) is often adequate (Rosenbaum 2010). Higher cumulative doses or prolonged therapy may be necessary in some cases; in one case report, an 11-year-old initially responded to 1.5 mg of physostigmine for antimuscarinic delirium and agitation with a good response. As the physostigmine effects diminished, agitation returned, which was unresponsive to benzodiazepines and required 4 additional 1 mg doses of physostigmine administered over 6 hours (Thornton 2016).
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection, as salicylate:
Generic: 1 mg/mL (2 mL)
Yes
IV: Infuse no more rapidly than 1 mg/minute. Too rapid administration may cause bradycardia, respiratory distress, and seizures. Slower administration (ie, over ≥5 minutes) may be preferable (Howland 2019). May also be administered IM (manufacturer's labeling).
Parenteral:
IM: May administer as undiluted solution.
IV: Infuse undiluted solution slowly; maximum rate: Pediatric patients: 0.5 mg/minute; a higher maximum rate in adults: 1 mg/minute. Slower administration (ie, over ≥5 minutes) may be preferable (Howland 2019). Too rapid administration can cause bradycardia and hypersalivation leading to respiratory distress and seizures.
Hazardous agent; use appropriate precautions for handling and disposal (EPA, P-listed).
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).
Physostigmine may be confused with Prostigmin, pyridostigmine
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined:
Cardiovascular: Bradycardia
Gastrointestinal: Nausea, salivation, vomiting
Nervous system: Seizures
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).
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.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
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. Risk C: Monitor therapy
Anticholinergic Agents: Acetylcholinesterase Inhibitors may diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Benoxinate: Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Benoxinate. Specifically, the effects of benoxinate may be prolonged. Risk C: Monitor therapy
Beta-Blockers: Acetylcholinesterase Inhibitors may enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
Cholinergic Agonists: Acetylcholinesterase Inhibitors may enhance the adverse/toxic effect of Cholinergic Agonists. Specifically, cholinergic effects may be enhanced or increased. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur. Risk C: Monitor therapy
Dipyridamole: May diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Neuromuscular-Blocking Agents (Nondepolarizing): Acetylcholinesterase Inhibitors may diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Succinylcholine: Acetylcholinesterase Inhibitors may enhance the neuromuscular-blocking effect of Succinylcholine. Risk C: Monitor therapy
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).
It is not known if physostigmine is excreted in breast milk. According to the manufacturer, the decision to continue or discontinue breast-feeding during therapy should take into account the risk of exposure to the infant and the benefits of treatment to the mother.
ECG, vital signs; consult individual institutional policies and procedures.
Note: The duration of action of some anticholinergic agents may exceed the duration of action of physostigmine; therefore, monitor closely for recurrence of symptoms (Howland 2019).
Physostigmine is a carbamate which inhibits the enzyme acetylcholinesterase and prolongs the central and peripheral effects of acetylcholine
Onset of action: Within 3 to 8 minutes
Duration: 45 to 60 minutes
Absorption: IM: Readily absorbed
Distribution: Widely distributed throughout the body; crosses blood-brain barrier readily and reverses both central and peripheral anticholinergic effects
Metabolism: Via hydrolysis by cholinesterases
Half-life elimination: 1 to 2 hours
Solution (Physostigmine Salicylate Injection)
1 mg/mL (per mL): $46.97
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