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Medication Safety Issues
Sound-alike/look-alike issues:
Physostigmine may be confused with Prostigmin®, pyridostigmine
Pronunciation
(fye zoe STIG meen)
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Reverse toxic, life-threatening delirium caused by atropine, diphenhydramine, dimenhydrinate, Atropa belladonna (deadly nightshade), or jimson weed (Datura spp)
Pregnancy Risk Factor
C
Lactation
Excretion in breast milk unknown
Contraindications
Hypersensitivity to physostigmine or any component of the formulation; GI or GU obstruction; asthma; gangrene; diabetes, cardiovascular disease; any vagotonic state; coadministration of choline esters and depolarizing neuromuscular-blocking agents
Warnings/Precautions
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.
• Cholinergic effects: Discontinue if symptoms of excess cholinergic activity (eg, salivation, sweating, urinary incontinence); overdosage may result in cholinergic crisis, which must be distinguished from myasthenic crisis.
• Hypersensitivity/overdose reactions: Due to the possibility of hypersensitivity or overdose/cholinergic crisis, atropine should be readily available.
Disease-related concerns:
• Anticholinergic toxicity: Not intended as a first-line agent for anticholinergic toxicity.
• Asthma: Use with caution in patients with asthma.
• Cardiovascular disease: Use with caution in patients with cardiovascular disease, including bradycardia.
• Diabetes: Use with caution in patients with diabetes mellitus.
• Gangrene: Use with caution in patients with gangrene.
• Parkinson's disease: Not intended as a first-line agent for Parkinson's disease.
• Seizure disorder: Use with caution in patients with a history of seizure disorder.
Concurrent drug therapy issues:
• Choline esters: Concomitant administration of choline esters is contraindicated.
• Depolarizing neuromuscular-blocking agents (ie, succinylcholine): Concomitant administration of depolarizing neuromuscular-blocking agents is contraindicated.
Dosage form specific issues:
• Benzyl alcohol: Products may contain benzyl alcohol which has been associated with "gasping syndrome" in neonates.
• Sodium bisulfate: Products may contain sodium bisulfate.
Other warnings/precautions:
• I.V. administration: Administer slowly over 5 minutes to prevent respiratory distress and seizures. Continuous infusions should never be used.
• 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.
Adverse Reactions
Frequency not defined.
Cardiovascular: Asystole, bradycardia, palpitation
Central nervous system: Hallucinations, nervousness, restlessness, seizure
Gastrointestinal: Diarrhea, nausea, salivation, stomach pain
Genitourinary: Urinary frequency
Neuromuscular & skeletal: Twitching
Ocular: Lacrimation, miosis
Respiratory: Bronchospasm, dyspnea, pulmonary edema, respiratory paralysis
Miscellaneous: Diaphoresis
Drug Interactions
Beta-Blockers: Acetylcholinesterase Inhibitors may enhance the bradycardic effect of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. Risk C: Monitor therapy
Cholinergic Agonists: Acetylcholinesterase Inhibitors may enhance the adverse/toxic effect of Cholinergic Agonists. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur. Risk C: Monitor therapy
Ginkgo Biloba: May enhance the adverse/toxic 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). Acetylcholinesterase Inhibitors may decrease the metabolism of Neuromuscular-Blocking Agents (Nondepolarizing). This is only true for mivacurium in which case the neuromuscular blocking effects might be prolonged. Risk C: Monitor therapy
Succinylcholine: Acetylcholinesterase Inhibitors may enhance the neuromuscular-blocking effect of Succinylcholine. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Herb/Nutraceutical: Ginkgo biloba may enhance the adverse/toxic effect of physostigmine; monitor.
Storage
Do not use solution if cloudy or dark brown.
Compatibility
Stable in dextran 6% in dextrose, dextran 6% in NS, D5W, D10W, D5LR, D51/4NS, D51/2NS, D5NS, fat emulsion 10%, LR, 1/2NS, NS.
Y-site administration: Compatible: Ampicillin, epinephrine, famotidine, heparin, hydrocortisone sodium succinate, potassium chloride, tolazoline, vitamin B complex with C. Incompatible: Dobutamine.
Compatibility in syringe: Compatible: Doxapram.
Compatibility when admixed: Compatible: Amikacin, chloramphenicol, cimetidine, netilmicin, sodium bicarbonate. Incompatible: Phenytoin, ranitidine. Variable (consult detailed reference): Oxytocin.
Mechanism of Action
Inhibits destruction of acetylcholine by acetylcholinesterase which facilitates transmission of impulses across myoneural junction and prolongs the central and peripheral effects of acetylcholine
Pharmacodynamics/Kinetics
Onset of action: ~5 minutes
Duration: 1-2 hours
Absorption: I.M.: Readily absorbed
Distribution: Crosses blood-brain barrier readily and reverses both central and peripheral anticholinergic effects
Metabolism: Hepatic and via hydrolysis by cholinesterases
Half-life elimination: 15-40 minutes
Dosage
Reversal of toxic anticholinergic effects: Note: Administer slowly over 5 minutes to prevent respiratory distress and seizures. Continuous infusions of physostigmine should never be used.
Children: Note: Reserve for life-threatening situations only: I.V.: 0.01-0.03 mg/kg/dose; may repeat after 5-10 minutes to a maximum total dose of 2 mg or until response occurs or adverse cholinergic effects occur
Adults: I.M., I.V.: 0.5-2 mg to start, repeat every 20 minutes until response occurs or adverse effect occurs; repeat 1-4 mg every 30-60 minutes as life-threatening symptoms recur
Administration: I.V.
Infuse slowly I.V. over 5 minutes. Too rapid administration can cause bradycardia and hypersalivation leading to respiratory distress and seizures.
Monitoring Parameters
ECG, vital signs
Test Interactions
Increased aminotransferase [ALT/AST] (S), increased amylase (S)
Patient Education
Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. May cause dizziness, drowsiness, or hypotension (rise slowly from sitting or lying position and use caution when driving or climbing stairs); vomiting or loss of appetite (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); or diarrhea (boiled milk, yogurt, or buttermilk may help). Report persistent abdominal discomfort; significantly increased salivation, sweating, tearing, or urination; flushed skin; chest pain or palpitations; acute headache; unresolved diarrhea; excessive fatigue, insomnia, dizziness, or depression; increased muscle, joint, or body pain; vision changes or blurred vision; or shortness of breath or wheezing. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.
Geriatric Considerations
See Warnings/Precautions.
Anesthesia and Critical Care Concerns/Other Considerations
Cholinergic effects of physostigmine include bradycardia and bradydysrhythmias.
Cardiovascular Considerations
Cholinergic effects of physostigmine include bradycardia and bradydysrhythmias.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Salivation.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause restlessness, nervousness, or hallucinations
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
When used to reverse neuromuscular block, patient must be monitored closely until full return of neuromuscular functioning. Assess bladder and sphincter adequacy prior to administering medication. Assess other medications patient may be taking for effectiveness and interactions. Monitor therapeutic effectiveness and adverse reactions (cholinergic crisis). Assess knowledge/teach patient appropriate use of ophthalmic forms, interventions to reduce side effects, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as salicylate: 1 mg/mL (2 mL) [contains benzyl alcohol and sodium metabisulfite]
References
Beaver KM and Gavin TJ, “Treatment of Acute Anticholinergic Poisoning With Physostigmine,” Am J Emerg Med, 1998, 16(5):505-7.
Burns MJ, Linden CH, Graudins A, et al, “A Comparison of Physostigmine and Benzodiazepines for the Treatment of Anticholinergic Poisoning,” Ann Emerg Med, 2000, 35(4):374-81.
Caine ED, “Anticholinergic Toxicity,” N Engl J Med, 1979, 300(22):1278.
Dysken MW and Janowsky DS, “Dose-Related Physostigmine-Induced Ventricular Arrhythmia: Case Report,” J Clin Psychiatry, 1985, 46(10):446-7.
Jenike MA, Albert MS, Heller H, et al, “Oral Physostigmine Treatment for Patients With Presenile and Senile Dementia of the Alzheimer's Type: A Double-Blind Placebo-Controlled Trial,” J Clin Psychiatry, 1990, 51(1):3-7.
Lugassy D, Manno R, and Barrueto, Jr F, “Diphenhydramine Overdose Reversed With Aggressive Physostigmine Administration,” Clin Toxicol (Phila), 2006, 44:715.
O'Donnell SJ, Burkhart KK, Donovan JW, et al, “Safety of Physostigmine Use for Anticholinergic Toxicity,” J Toxicol Clin Toxicol, 2002, 40(5):684.
Pentel P and Peterson CD, “Asystole Complicating Physostigmine Treatment of Tricyclic Antidepressant Overdose,” Ann Emerg Med, 1980, 9(11):588-90.
Theesen KA, Boyd JA, “Dementia of the Alzheimer's Type: An Update,” Consult Pharm, 1990, 5:535-40.
International Brand Names
Lexi-Comp.com
Last full review/revision August 2008
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