Class: Parasympathomimetic (Cholinergic) Agents
VA Class: AU300
CAS Number: 57-64-7
Brands: Antilirium
Introduction
Reversible anticholinesterase agent.a
Uses for Physostigmine Salicylate
Reversal of Anticholinergic Effects
Carefully weigh risks and potential benefits of physostigmine therapy when making individual decisions about its use since serious adverse effects (including seizures and asystole) may occur with physostigmine therapy.109 148 149 150 151 152 153 156 157 158 159 a
The manufacturers state that physostigmine is used to reverse CNS effects resulting from clinical or toxic dosages of drugs (e.g., some antihistamines, antimuscarinics, antiparkinsonian agents, phenothiazines) capable of producing anticholinergic syndrome148 149 a b and from intoxication with certain plants (e.g., Atropa belladonna [deadly nightshade], Brugmansia species [angels’ trumpet], Datura stramonium [jimsonweed, thorn apple, locoweed], Lantana camara).139 148 149 a b However, routine use not recommended because of potentially serious adverse effects (e.g., seizures, bronchospasm, bradycardia, asystole); many clinicians advise to reserve use for treatment of severe or life-threatening symptoms (e.g., extensive delirium or agitation, hallucinations, hyperthermia, severe sinus or supraventricular tachycardia, seizures) in patients who fail to respond to alternative therapy.139 140 141 142 143 144 147 148 149 150 151 152 a
Has also been used successfully in the treatment of tricyclic antidepressant-induced anticholinergic toxicity,109 147 151 152 153 154 155 156 157 159 160 but currently is rarely used because of potentially serious adverse effects (seizures, bronchospasm, bradycardia, asystole).109 147 150 151 152 153 156 157 158 159 Precise role controversial; most clinicians advise against the routine use of physostigmine in tricyclic intoxication,109 147 151 152 153 154 155 156 157 158 159 161 and some clinicians recommend to reserve use only for life-threatening anticholinergic symptoms refractory to other treatment.109 153 157
Treatment to reverse anticholinergic effects (e.g., delirium, prolonged somnolence) produced by atropine and/or scopolamine preanesthetic medications.b
Alzheimer’s Disease
Has been used with variable results in the treatment of dementia of the Alzheimer’s type† (Alzheimer’s disease), alone or combined with lecithin.117 118 119 120 121 122 123 124 125 126 127 128 129 130 131
HereditaryAtaxias
Has been used for the treatment of Friedreich’s ataxia and other hereditary ataxias† (spinocerebellar degenerations)135 136 137 138 (designated an orphan drug by FDA for these uses).135
Physostigmine Salicylate Dosage and Administration
General
Atropine sulfate injection should always be readily available.149 (See Cautions.)
Administration
Administer by slow IV injection or by IM injection;149 has also been administered by sub-Q injection and orally†.b
Oral Administration
Oral dosage form not currently commercially available.b
IV Administration
Rate of Administration
Administer at a slow, controlled rate: ≤1 mg/minute in adults and ≤0.5 mg/minute in children.149 (See Reversal of Anticholinergic Effects under Uses and also see Rapid IV Administration under Cautions.)
Dosage
Available as physostigmine salicylate; dosage expressed in terms of the salt.149 b
Pediatric Patients
Reversal of Anticholinergic Effects
IV
Initially, 0.02 mg/kg;149 if no response, repeat dose at 5- to 10-minute intervals until response occurs, adverse cholinergic effects develop, or a total dose of 2 mg has been administered.149 Alternatively, 0.03 mg/kg or 0.9 mg/m2, as necessary.b
IM
Initially, 0.02 mg/kg;149 if no response, repeat dose at 5- to 10-minute intervals until response occurs, adverse cholinergic effects develop, or a total dose of 2 mg has been administered.149 Alternatively, 0.03 mg/kg or 0.9 mg/m2, as necessary.b
Adults
Reversal of Anticholinergic Effects
IV
Initially, 0.5–2 mg;b may repeat dose every 20 minutes until response occurs or adverse cholinergic effects occur.b If initial doses are effective, administer 1–4 mg, as necessary, at intervals (usually 30–60 minutes) as life-threatening signs (e.g., arrhythmias, seizures, deep coma) recur.b
To reverse anticholinergic effects of atropine or scopolamine preanesthetic medications, administer a dose twice that of the anticholinergic drug, on a weight basis.b
IM
Initially, 0.5–2 mg;b may repeat dose every 20 minutes until response occurs or adverse cholinergic effects occur.b If initial doses are effective, administer 1–4 mg, as necessary, at intervals (usually 30–60 minutes) as life-threatening signs (e.g., arrhythmias, seizures, deep coma) recur.b
To reverse anticholinergic effects of atropine or scopolamine preanesthetic medications, administer a dose twice that of the anticholinergic drug, on a weight basis.b
Alzheimer’s Disease†
Oral†
Usually has been initiated at dosage of 0.5 mg given every 2 hours 6 or 7 times daily until beneficial effect is achieved, intolerable adverse effects occur, or a maximum total daily dose of 16 mg is achieved.119 120 121 130
Dosage of 2–2.5 mg every 2 hours 6 or 7 times daily also has been used.118 119 120 121 130
Prescribing Limits
Pediatric Patients
Reversal of Anticholinergic Effects
IV
Maximum total dose of 2 mg.149
IM
Maximum total dose of 2 mg.149
Adults
Alzheimer’s Disease†
Oral†
Maximum 16 mg daily.121
Cautions for Physostigmine Salicylate
Contraindications
Asthma.149 b
Gangrene.149 b
Diabetes.149 b
Cardiovascular disease.149 b
Mechanical obstruction of the intestinal or urogenital tract.149 b
Any vagotonic state.149 b
Concomitant use of choline esters (e.g., methacholine, bethanechol) or depolarizing neuromuscular blocking agents (e.g., succinylcholine).149 b
Known hypersensitivity to physostigmine or any ingredient in the formulation.
Warnings/Precautions
Warnings
Cholinergic Crisis
Overdosage may result in cholinergic crisis (e.g., excessive salivation and sweating, miosis, nausea, vomiting, diarrhea, bradycardia or tachycardia, hypotension or hypertension, confusion, seizures, coma, severe muscle weakness, paralysis).149 b If overdosage occurs, mechanical ventilation with repeated bronchial aspiration and IV atropine are recommended.149 b
Rapid IV Administration
Possible bradycardia, hypersalivation leading to respiratory problems, and/or seizures associated with rapid IV administration; asystole also has been reported.148 149 150 151 a Administer at a slow controlled rate.149 (See IV Administration under Dosage and Administration.)
Parasympathetic Stimulation
Discontinue therapy if excessive salivation, vomiting, urination, or defecation occurs.149 b Reduce dosage if excessive sweating or nausea occurs.149 b Atropine sulfate injection should always be readily available.149 Observe patient for evidence of bronchial constriction; perform cardiac monitoring.141 142 144
Sensitivity Reactions
Sulfite Sensitivity
Injections may contain sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.149
General Precautions
Concomitant Diseases
Use with caution in patients with epilepsy, parkinsonian syndrome, or bradycardia.b
Specific Populations
Pregnancy
Category C.c
Lactation
Safety not established in nursing women.149
Pediatric Use
Reserve use for life-threatening situations only.b
Common Adverse Effects
Nausea,149 vomiting,149 epigastric pain,b miosis,b salivation,149 sweating,b lacrimation,b dyspnea,b bronchospasm.b
Physostigmine Salicylate Pharmacokinetics
Absorption
Bioavailability
Readily absorbed from the GI tract, mucous membranes, and subcutaneous tissue.b
Following oral administration (oral dosage form not currently commercially available), physostigmine may undergo saturable metabolism prior to reaching the systemic circulation.100 101 102 103
Onset
Following parenteral administration, 3–8 minutes.b
Duration
Following parenteral administration, 30 minutes to 5 hours.b
Distribution
Extent
Widely distributed throughout the body;b readily penetrates the blood-brain barrier.149 b
Elimination
Metabolism
Metabolized via hydrolysis by cholinesterases.b
Elimination Route
Not fully elucidated; very small amounts excreted in urine.b
Half-life
15–40 minutes.100 101
Stability
Storage
Parenteral
Injection
15–30°C.149 b
ActionsActions
Inhibits acetylcholinesterase and prolongs and exaggerates the central and peripheral effects of acetylcholine.149 b
Produces generalized cholinergic responses including miosis, increased tonus of intestinal musculature, constriction of bronchi, and stimulation of secretion by salivary and sweat glands.b
At sufficiently high dosage, directly blocks action at autonomic ganglia, causes muscle fasciculation and, ultimately, depolarization block.b
Some evidence that physostigmine may potentiate cholinergic mechanisms involved in memory storage and may improve short-term memory.b
Advice to Patients
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.149
Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.149
Importance of informing patients of other important precautionary information.149 (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Bulk | Powder* | |||
Parenteral | Injection | 1 mg/mL* | Physostigmine Salicylate Injection | Akorn |
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions April 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
References
Only references cited for selected revisions after 1984 are available electronically.
100. Whelpton R, Hurst P. Bioavailability of oral physostigmine. N Engl J Med. 1985; 313:1293-4. [IDIS 206353] [PubMed 4058515]
101. Gibson M, Moore T, Smith CM et al. Physostigmine concentrations after oral doses. Lancet. 1985; 1:695-6. [IDIS 197977] [PubMed 2858639]
102. Sharpless NS, Thal LJ. Plasma physostigmine concentrations after oral administration. Lancet. 1:1397-8. Letter.
103. Avant GR, Speeg KV, Freemon FR et al. Physostigmine reversal of diazepam-induced hypnosis: a study in human volunteers. Ann Intern Med. 1979; 91:53-5. [PubMed 380427]
104. Bidwai AV, Stanley TH, Rogers C et al. Reversal of diazepam-induced postanesthetic somnolence with physostigmine. Anesthesiology. 1979; 51:256-9. [PubMed 475028]
105. Rupreht J. Physostigmine reversal of diazepam. Anesthesiology. 1980; 53:180-1. [IDIS 118582] [PubMed 7416534]
106. Spaulding BC, Choi SD, Gross JB et al. The effect of physostigmine on diazepam-induced ventilatory depression: a double-blind study. Anesthesiology. 1984; 61:551-4. [IDIS 192534] [PubMed 6437287]
107. Bourke DL, Rosenberg M, Allen PD. Physostigmine: effectiveness as an antagonist of respiratory depression and psychomotor effects caused by morphine or diazepam. Anesthesiology. 1984; 61:523-8. [IDIS 192533] [PubMed 6437286]
108. Garber JG, Ominsky AJ, Orkin FK. Physostigmine reversal of diazepam sedation. Anesthesiology. 1979; 51(Suppl 3):S37. [IDIS 106623] [PubMed 484899]
109. Gosselin RE, Smith RP, Hodge HC. Clinical toxicology of commercial products. 5th ed. Baltimore: Williams & Wilkins; 1984:III-138-41.
110. Nilsson E. Physostigmine treatment in various drug-induced intoxications. Ann Clin Res. 1982; 14:165-72. [PubMed 7168546]
111. Ongini E, Parravicini L, Bamonte F. Effects of physostigmine on benzodiazepine toxicity. Arch Int Pharmacodyn Ther. 1981; 253:164-76. [PubMed 7325753]
112. Nagy J, Decsi L. Physostigmine, a highly potent antidote for acute experimental diazepam intoxication. Neuropharmacology. 1978; 17:469-75. [PubMed 692813]
113. Walz MA, Davis WM. Experimental diazepam intoxication in rodents: physostigmine and naloxone as potential antagonists. Drug Chem Toxicol. 1979; 2:257-67. [PubMed 546626]
114. DiLiberti J, O’Brien ML, Turner T. Use of physostigmine as an antidote in accidental diazepam intoxication. J Pediatr. 1975; 86:106-7. [PubMed 1110430]
115. Blitt CD, Petty WC. Reversal of lorazepam delirium by physostigmine. Anesth Analg. 1975; 54:607-8. [PubMed 241267]
116. Caldwell CB, Gross JB. Physostigmine reversal of midazolam-induced sedation. Anesthesiology. 1982; 57:125-7. [IDIS 156369] [PubMed 7091735]
117. Erwin WG. Senile dementia of the Alzheimer type. Clin Pharm. 1984; 3:497-504. [IDIS 190836] [PubMed 6149031]
118. Blass JP, Weksler ME. Toward an effective treatment of Alzheimer’s disease. Ann Intern Med. 1983; 98:251-3. [IDIS 164935] [PubMed 6824261]
119. Mohs RC, Davis BM, Johns CA et al. Oral physostigmine treatment of patients with Alzheimer’s disease. Am J Psychiatry. 1985; 142:28-33. [IDIS 194743] [PubMed 3881051]
120. Davis KL, Mohs RC, Rosen WG et al. Memory enhancement with oral physostigmine in Alzheimer’s disease. N Engl J Med. 1983; 308:721. [IDIS 167362] [PubMed 6338389]
121. Thal LJ, Fuld PA. Memory enhancement with oral physostigmine in Alzheimer’s disease. N Engl J Med. 1983; 308:720. [IDIS 167360] [PubMed 6338388]
122. Smith CM, Swash M. Physostigmine in Alzheimer’s disease. Lancet. 1979; 1:42. [PubMed 83485]
123. Mohs RC, Davis KL. A signal detectability analysis of the effect of physostigmine on memory in patients with Alzheimer’s disease. Neurobiol Aging. 1982; 3:105-10. [PubMed 6752738]
124. Davis KL, Mohs RC. Enhancement of memory processes in Alzheimer’s disease with multiple-dose intravenous physostigmine. Am J Psychiatry. 1982; 139:1421-4. [IDIS 160992] [PubMed 6753611]
125. Davis KL, Mohs RC. Enhancement of memory by physostigmine. N Engl J Med. 1979; 301:946. [PubMed 481551]
126. Goodnick P, Gershon S. Chemotherapy of cognitive disorders in geriatric subjects. J Clin Psychiatry. 1984; 45:196-209. [IDIS 185785] [PubMed 6327657]
127. Levin HS, Peters BH. Long-term administration of oral physostigmine and lecithin improve memory in Alzheimer’s disease. Ann Neurol. 1984; 15:210. [IDIS 181463] [PubMed 6703661]
128. Thal LJ, Fuld PA, Masur DM et al. Long-term administration of oral physostigmine and lecithin improve memory in Alzheimer’s disease. Ann Neurol. 1984; 15:210.
129. Caltagirone C, Gainotti G, Masullo C. Oral administration of chronic physostigmine does not improve cognitive or mnesic performances in Alzheimer’s presenile dementia. Int J Neurosci. 1982; 16:247-9. [PubMed 7169287]
130. Beller SA, Overall JE, Swann AC. Efficacy of oral physostigmine in primary degenerative dementia: a double-blind study of response to different dose level. Psychopharmacology. 1985; 87:147-51. [PubMed 3931138]
131. Denber HCB. Physostigmine in the treatment of memory disorders: a case report. Psychiatr J Univ Ottawa. 1982; 7:8-12.
132. Ashford JW, Soldinger S, Schaeffer J et al. Physostigmine and its effect on six patients with dementia. Am J Psychiatry. 1981; 138:829-30. [IDIS 134250] [PubMed 7246817]
133. Dysken MW, Janowsky DS. Dose-related physostigmine-induced ventricular arrhythmia: case report. J Clin Psychiatry. 1985; 46:446-7. [IDIS 207871] [PubMed 4044537]
134. Cain JW. Hypertension associated with oral administration of physostigmine in a patient with Alzheimer’s disease. Am J Psychiatry. 1986; 143:910-2. [IDIS 217891] [PubMed 3717434]
135. Food and Drug Administration. Cumulative list of orphan drug and biological designations. Fed Regist. 1987; 52:3778-81.
136. Kark RAP, Blass JP, Spence MA. Physostigmine in familial ataxias. Neurology. 1977; 27:70-2. [PubMed 556821]
137. Rodriguez-Budelli MM, Kark RAP, Blass JP et al. Action of physostigmine on inherited ataxias. Adv Neurol. 1978; 21:195-202. [PubMed 735925]
138. Tijssen CC, Endtz LJ, Goor C. The influence of physostigmine on visual-vestibular interaction in hereditary ataxias. J Neurol Neurosurg Psychiatry. 1985; 48:977-81. [PubMed 3877148]
139. DeManuelle MS. Systemic poisonous plant intoxication. In: Viccellio P, ed. Handbook of medical toxicology. New York: Little, Brown and Company; 1993:710-21.
140. American Psychiatric Association. Practice guideline for the treatment of patients with delirium. Am J Psychiatr. 1999; 156:1-20.
141. Trujillo MH, Guerrero J, Fragachan C et al. Pharmacologic antidotes in critical care medicine: a practical guide for drug administration. Crit Care Med. 1998; 26:377-91. [IDIS 401015] [PubMed 9468179]
142. Receptor toxicology. In: Ellenhorn MJ, Schonwald S, Ordog G et al, eds. Ellenhorn’s medical toxicology: diagnosis and treatment of human poisoning. 2nd ed. Baltimore: Williams & Wilkins; 1997:840-61.
143. Bowden CA, Krenzelok EP. Clinical applications of commonly used contemporary antidotes: a US perspective. Drug Saf. 1997; 16:9-47. [PubMed 9010641]
144. Hastings OM. Muscle relaxants. In: Viccellio P, ed. Handbook of medical toxicology. New York: Little, Brown and Company; 1993:473-84.
145. Silverman R. Tricyclic and newer antidepressants. In: Viccellio P, ed. Handbook of medical toxicology. New York: Little, Brown and Company; 1993:540-51.
146. American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry. 2004; 161(2 Suppl):1-56.
147. Woolf AD, Erdman AR, Nelson LS et al. Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol. 2007; 45:203-33.
148. Taylor Pharmaceuticals. Physostigmine salicylate injection prescribing information. Decatur, IL; 2006 Mar.
149. Forest Pharmaceuticals. Antilirium (physostigmine salicylate) injection prescribing information. In: Physicians' desk reference. 52nd ed. Montvale, NJ: Medical Economics Company Inc; 1998:944-5.
150. Pentel P, Peterson CD. Asystole complicating physostigmine treatment of tricyclic antidepressant overdose. Ann Emerg Med. 1980; 9:588-90. [PubMed 7001962]
151. Suchard JR. Assessing physostigmine's contraindication in cyclic antidepressant ingestions. J Emerg Med. 2003; 25:185-91. [PubMed 12902007]
152. Pentel PR, Benowitz NL. Tricyclic antidepressant poisoning: management of arrhythmias. Med Toxicol. 1986; 1:101-21. [IDIS 221648] [PubMed 3784839]
153. Crome P. Poisoning due to tricyclic antidepressant overdosage: clinical presentation and treatment. Med Toxicol. 1986; 1:261-85. [IDIS 222612] [PubMed 3537621]
154. Marshall JB, Forker AD. Cardiovascular effects of tricyclic antidepressant drugs: therapeutic usage, overdose, and management of complications. Am Heart J. 1982; 103:401-14. [IDIS 145664] [PubMed 7039280]
155. Jackson JE, Bressler R. Prescribing tricyclic antidepressants. Part III: management of overdose. Drug Therapy. 1982; 12:175-89.
156. Goldfrank LR, Lewin NA, Flomenbaum NE et al. Psychotropics: antidepressants: tricyclics, tetracyclics, monoamine oxidase inhibitors, and others. In: Goldfrank LR, Flomenbaum NE, Lewin NA et al, eds. Goldfrank’s toxicologic emergencies. 3rd ed. Norwalk, CT: Appleton-Century-Crofts; 1986:351-9.
157. Braden NJ, Jackson JE, Walson PD. Tricyclic antidepressant overdose. Ped Clin North Am. 1986; 33:287-98.
158. The American Heart Association. Guidelines 2005 for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2005; 112(Suppl I): IV1-211. [PubMed 16314375]
159. Newton RW. Physostigmine salicylate in the treatment of tricyclic antidepressant overdosage. JAMA. 1975; 231:941-3. [PubMed 1173100]
160. Holinger PC, Klawans HL. Reversal of tricyclic-overdosage-induced central anticholnegic syndrome by physostigmine. Am J Psychiatry. 1976; 133:1018-23. [PubMed 961921]
161. Hollister LE. Drug therapy: tricyclic antidepressants (second of two parts). N Engl J Med. 1978; 299:1168-72. [PubMed 703806]
a. Forest Pharmaceuticals. Antilirium (physostigmine salicylate) injection prescribing information. In: Physicians' desk reference. 53rd ed. Montvale, NJ: Medical Economics Company Inc; 1999:1018.
b. AHFS Drug Information 2008. McEvoy GK, ed. Physostigmine salicylate. Bethesda, MD: American Society of Health-System Pharmacists; 2007: 1284-6.
c. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1998:866-7.
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