Physostigmine
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Drug Name: Physostigmine
Therapeutic Class: Cholinergic (Parasympathomimetic) Agent
Subclass: Cholinesterase Inhibitor (Reversible, Tertiary Amine)
Speciality: Emergency Medicine
Schedule: Schedule H
Routes: Intravenous (preferred), Intramuscular (alternative)
Formulations:
- Injection: 1 mg/mL (2 mL ampoule) — as physostigmine salicylate
- Note: Limited commercial availability; primarily sourced through hospital pharmacy or specialty poison control centres
ADULT INDICATIONS + DOSING
Primary Indications (Approved / Standard in India)
1. Life-threatening Anticholinergic Toxidrome (Central + Peripheral Manifestations)
Causative agents include:
- Atropine and related alkaloids
- Antihistamines (diphenhydramine, promethazine)
- Tricyclic antidepressants (amitriptyline, imipramine) — with specific precautions
- Antipsychotics with anticholinergic properties
- Antispasmodics (dicyclomine, hyoscine)
- Plant toxins (Datura, Atropa belladonna)
Pre-treatment Requirements:
- Confirm anticholinergic toxidrome: delirium, agitation, mydriasis, dry skin, tachycardia, urinary retention, hyperthermia
- Obtain 12-lead ECG: MUST rule out QRS widening (>100 ms) before use
- Have atropine drawn and ready for reversal of cholinergic excess
Adult Dosing:
| Parameter | Details |
|---|---|
|
Starting dose
|
0.5–1 mg IV slowly over 5 minutes (not faster) |
|
Titration
|
Repeat 0.5–1 mg IV every 10–15 minutes if symptoms persist |
|
Usual maintenance dose
|
Not applicable (single or repeated bolus therapy) |
|
Maximum dose
|
2 mg per dose; total cumulative dose usually ≤4 mg |
IM Route (when IV access unavailable):
| Parameter | Details |
|---|---|
|
Starting dose
|
1–2 mg IM |
|
Titration
|
Not applicable (slower onset; assess response after 20–30 minutes) |
|
Usual maintenance dose
|
Not applicable |
|
Maximum dose
|
2 mg per dose |
Clinical Notes:
- Onset of action: IV 3–5 minutes; IM 10–20 minutes
- Duration of effect: 30–60 minutes; symptoms may recur as physostigmine wears off
- Repeat dosing often necessary until toxin is eliminated
- Response: Reversal of central effects (delirium, agitation) and peripheral effects (tachycardia, mydriasis)
- Use ONLY in life-threatening situations (severe agitation/delirium, hyperthermia, seizures, arrhythmias)
- NOT effective in pure adrenergic, opioid, or sedative-hypnotic toxicity
Secondary Indications — Adults (Off-label)
| Indication | Dose | Duration | Evidence Basis | Notes |
|---|---|---|---|---|
| Central anticholinergic syndrome (post-anaesthesia) | 0.5–1 mg IV over 5 minutes; may repeat once after 10–15 minutes | Single use | Neuroanaesthesia protocols; observational studies |
OFF-LABEL; Specialist (anaesthesiologist) only; for emergence delirium attributed to anticholinergic agents
|
| Reversal of CNS effects of atropine premedication | 0.5 mg IV slowly | Single dose | Anaesthesia practice |
OFF-LABEL; Rarely needed
|
PAEDIATRIC DOSING (Specialist Only)
Primary Indications (Approved / Standard in India)
1. Life-threatening Anticholinergic Toxicity
Common causes in children:
- Accidental ingestion of Datura seeds or preparations
- Antihistamine overdose
- Atropine-containing eye drops or medications
| Age Group | Starting Dose | Repeat Dose | Maximum per Administration |
|---|---|---|---|
| Infants 6 months–2 years | 0.02 mg/kg IV slowly over 5 minutes | May repeat every 10–15 minutes | 0.5 mg total |
| Children 2–12 years | 0.02 mg/kg IV slowly over 5 minutes | May repeat every 10–15 minutes | 2 mg total |
| Adolescents >12 years | 0.5–1 mg IV slowly | May repeat 0.5 mg every 10–15 minutes | 2 mg per dose |
| Parameter | Details |
|---|---|
|
Starting dose
|
0.02 mg/kg IV (minimum 0.1 mg) |
|
Titration
|
Repeat same dose every 10–15 minutes if inadequate response |
|
Usual maintenance dose
|
Not applicable |
|
Maximum dose
|
0.5 mg total in infants; 2 mg total in children |
Clinical Notes:
- Must be administered in ICU or monitored emergency setting
- Continuous cardiac and respiratory monitoring mandatory
- Have atropine (0.02 mg/kg) drawn and ready
- Paediatric poison control consultation recommended
Safety Monitoring:
- Continuous ECG monitoring
- Heart rate and rhythm (bradycardia risk)
- Respiratory status (bronchospasm, increased secretions)
- Level of consciousness
- Signs of cholinergic excess (SLUDGE: Salivation, Lacrimation, Urination, Defecation, GI upset, Emesis)
Secondary Indications — Paediatrics (Off-label)
| Indication | Dose | Evidence Basis | Notes |
|---|---|---|---|
| Post-anaesthesia emergence delirium (anticholinergic aetiology) | 0.01–0.02 mg/kg IV once | Limited anaesthesia case series |
OFF-LABEL; Specialist (paediatric anaesthesiologist) only; not routine practice
|
Age Restriction Statement:
- Not recommended in infants below 6 months except in life-threatening situations under specialist toxicology/ICU supervision
- Neonatal use: Avoid; extremely limited safety data
Renal Adjustments
- No dose adjustment required
- Physostigmine is primarily metabolised by plasma cholinesterases and tissue esterases
- Renal excretion plays minor role in elimination
Hepatic Adjustments
| Severity | Recommendation |
|---|---|
|
Mild impairment
|
No dose adjustment required |
|
Moderate impairment
|
Use with caution; slower titration; monitor closely for prolonged effect |
|
Severe impairment
|
Avoid if possible; if essential, use lowest effective dose under specialist supervision |
Contraindications
- Known hypersensitivity to physostigmine salicylate or any excipient
- Tricyclic antidepressant overdose with QRS widening (>100 ms) — risk of asystole and intractable seizures
- Bronchial asthma or reactive airway disease
- Mechanical gastrointestinal obstruction
- Mechanical urinary tract obstruction
- Gangrene or compromised intestinal blood flow
- Parkinson's disease or parkinsonian syndromes
- Concurrent use with depolarising neuromuscular blockers (suxamethonium)
- Concurrent use with choline esters or other cholinesterase inhibitors
Cautions
- Seizure disorders or history of seizures
- Bradyarrhythmias or cardiac conduction abnormalities
- Co-ingestion of multiple substances (mixed overdose) — may precipitate withdrawal or unmask other toxidromes
- Recent myocardial infarction
- Peptic ulcer disease
- Hyperthyroidism
- Vagotonia
- Diabetes mellitus (may affect glucose regulation)
- Elderly patients (increased sensitivity)
- Narrow therapeutic window — careful dose titration essential
- Rapid IV push can precipitate cholinergic crisis
Pregnancy
| Parameter | Recommendation |
|---|---|
|
Risk category
|
Limited human data; no formal classification in India |
|
Preferred alternatives
|
Supportive care; benzodiazepines for agitation; cooling measures for hyperthermia |
|
When may be used
|
Only in life-threatening maternal anticholinergic toxicity where benefit clearly outweighs risk |
|
Monitoring
|
Maternal heart rate, blood pressure; fetal heart rate monitoring; uterine activity |
Lactation
| Parameter | Recommendation |
|---|---|
|
Compatibility
|
Likely compatible for single/limited use (emergency indication) |
|
Drug levels in milk
|
Unknown; expected to be low due to short half-life and single-dose use |
|
Preferred alternatives
|
Supportive care preferred; if physostigmine essential, temporary interruption of breastfeeding not usually necessary |
|
Infant monitoring
|
If breastfeeding continues: observe for excessive salivation, diarrhoea, feeding difficulty, unusual drowsiness |
Elderly
| Parameter | Recommendation |
|---|---|
|
Starting dose
|
0.5 mg IV slowly over 5 minutes |
|
Titration
|
Slower titration; extend interval between doses to 15–20 minutes |
|
Special risks
|
Increased susceptibility to bradycardia, hypotension, falls, paradoxical agitation, confusion; often have underlying cardiac disease; may have reduced cholinesterase activity |
|
Precautions
|
ECG monitoring essential; lower threshold for considering contraindications; cognitive baseline assessment before and after |
Major Drug Interactions
| Interacting Drug | Effect | Recommendation |
|---|---|---|
|
Tricyclic antidepressants(amitriptyline, imipramine)
|
Risk of asystole, intractable seizures if QRS widened | Contraindicated if QRS >100 ms; use extreme caution even with normal QRS |
|
Depolarising neuromuscular blockers(suxamethonium)
|
Prolonged neuromuscular blockade | Avoid concurrent use |
|
Other cholinesterase inhibitors(neostigmine, pyridostigmine, donepezil)
|
Additive cholinergic toxicity; cholinergic crisis risk | Avoid combination |
|
Beta-blockers
|
Additive bradycardia; risk of severe bradycardia or heart block | Use with extreme caution; continuous cardiac monitoring |
|
Digoxin
|
Additive bradycardia and AV block | Use with caution; ECG monitoring |
|
Choline esters (bethanechol, carbachol)
|
Additive cholinergic effects | Avoid concurrent use |
Moderate Drug Interactions
| Interacting Drug | Effect | Recommendation |
|---|---|---|
|
Antihistamines (diphenhydramine, promethazine)
|
These are often the causative agents; physostigmine reverses their effects | Expected interaction; therapeutic intent |
|
Antipsychotics (chlorpromazine, olanzapine)
|
May mask toxidrome assessment; possible anticholinergic burden | Note in history; careful assessment |
|
Benzodiazepines
|
May reduce seizure risk from cholinergic excess | Beneficial co-administration in toxidrome management |
|
MAO inhibitors
|
Theoretical interaction in mixed overdoses | Careful toxidrome assessment |
|
Opioids
|
May mask mixed toxidrome features | Assess for concurrent opioid toxicity |
Common Adverse Effects
- Nausea and vomiting
- Abdominal cramps
- Increased salivation
- Lacrimation
- Sweating
- Bradycardia (mild)
- Dizziness
- Headache
- Miosis
Serious Adverse Effects
| Adverse Effect | Clinical Action |
|---|---|
|
Cholinergic crisis (excessive salivation, lacrimation, urination, defecation, GI cramping, emesis — "SLUDGE")
|
Stop administration immediately; IV atropine 1–2 mg; supportive care |
|
Severe bradycardia / Asystole
|
Stop immediately; IV atropine; ACLS protocol if needed |
|
Seizures
|
Stop immediately; IV benzodiazepines (diazepam 5–10 mg or lorazepam 2–4 mg); airway protection |
|
Bronchospasm
|
Stop immediately; bronchodilators; atropine if needed; oxygen |
|
Respiratory depression
|
Stop immediately; airway management; ventilatory support |
|
Hypotension
|
IV fluids; atropine if bradycardia-related |
Monitoring requirements
| Phase | Parameters |
|---|---|
|
Pre-treatment (Baseline)
|
12-lead ECG (QRS duration mandatory — contraindicated if >100 ms); heart rate; blood pressure; respiratory rate; oxygen saturation; mental status; temperature; pupil size |
|
During administration
|
Continuous cardiac monitoring (ECG, HR); blood pressure every 5 minutes; SpO₂; respiratory status; mental status changes; watch for cholinergic excess |
|
Post-dose (0–60 minutes)
|
Recurrence of anticholinergic symptoms (physostigmine effect wears off in 30–60 minutes); heart rate; need for repeat dosing |
|
Extended monitoring
|
Serial ECGs if TCA involvement; electrolytes; ABG if respiratory concerns; toxicology panel as indicated |
Brands in India
| Brand Name | Manufacturer | Formulation |
|---|---|---|
| Physolin | Samarth Life Sciences | Injection 1 mg/mL (2 mL) |
| Antichol | United Biotech | Injection 1 mg/mL (2 mL) |
Notes:
- Limited commercial availability
- Primarily hospital/institutional supply
- May require special order through poison control centres or tertiary care pharmacies
- No fixed-dose combinations available
Price Range (INR)
| Formulation | Approximate Price |
|---|---|
| Injection 1 mg/mL (2 mL ampoule) | ₹60–150 per ampoule |
- Not included in NLEM 2022
- Not under NPPA price control
- Available mainly in tertiary care/emergency settings and poison control centres
- Price varies significantly based on availability and source
Clinical Pearls
- ECG before every dose — Never administer physostigmine in suspected TCA overdose without confirming QRS <100 ms; QRS widening is an absolute contraindication due to risk of asystole.
- True anticholinergic toxidrome required — Confirm classic features before use: "Hot as a hare, blind as a bat, dry as a bone, red as a beet, mad as a hatter" (hyperthermia, mydriasis, dry skin/mucosa, flushing, delirium).
- Short duration demands vigilance — Effect lasts only 30–60 minutes; symptoms often recur as physostigmine is eliminated. Plan for repeat dosing and continued monitoring.
- Atropine is the antidote — Always have atropine 1–2 mg IV drawn and ready; can reverse physostigmine-induced cholinergic crisis immediately.
- Slow IV push is non-negotiable — Administer over at least 5 minutes; rapid injection causes severe cholinergic reactions including seizures and bradyarrhythmias.
- Consult poison control — Given limited use and narrow therapeutic window, expert consultation from poison control centres is advisable before administration.
Version
RxIndia v1.0 — 01 Feb 2026
References
- Indian Pharmacopoeia 2018
- National Formulary of India 2021
- AIIMS Delhi Poison Management Guidelines
- API Textbook of Medicine — Toxicology chapter
- Harrison's Principles of Internal Medicine, 21st Edition — Poisoning and Drug Overdose
- Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th Edition
- ICMR-PGTCC Delhi Antidote Access Protocol
- Indian Emergency Medicine clinical protocols
Last Updated: 01/02/2026
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This platform is designed strictly for healthcare professionals. Data provided is synthesized from authoritative pharmacological sources and clinical registries. Do not use for consumer medical decisions. Always verify critical dosing and contraindications with official institutional protocols and peer-reviewed journals.
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