Elephant Formulary

© 2003-17 Susan K. Mikota DVM and Donald C. Plumb, Pharm.D. Published by
Elephant Care International

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Elephant specific information, if available, is in blue.


Chemistry – Synthetic quaternary ammonium parasympathomimetic agents, neostigmine bromide and neostigmine methylsulfate both occur as odorless, bitter-tasting, white, crys­talline powders that are very soluble in water and soluble in alcohol. The melting point of neostigmine methylsulfate is from 144-149°. The pH of the commercially available neostigmine methylsulfate injection is from 5-6.5.


Storage/Stability/Compatibility – Neostigmine bromide tablets should be stored at room temperature in tight containers. Neostigmine methylsulfate injection should be stored at room temperature and protected from light; avoid freezing.


Neostigmine methylsulfate injection is reportedly compatible with the commonly used IV replacement solutions and the following drugs: glycopyrrolate, pentobarbital sodium, and thiopental sodium.


Pharmacology – Neostigmine competes with acetylcholine for acetylcholinesterase. As the neostigmine-acetylcholinesterase complex is hydrolyzed at a slower rate than that of the acetylcholine-enzyme complex, acetylcholine will accumulate with a resultant exag­geration and prolongation of its effects. These effects can include increased tone of in­testinal and skeletal musculature, stimulation of salivary and sweat glands, bronchocon­striction, ureter constriction, miosis and bradycardia. Neostigmine also has a direct choli­nomimetic effect on skeletal muscle.


Uses/Indications – Neostigmine is indicated for rumen atony, initiating peristalsis, empty­ing the bladder and stimulating skeletal muscle contractions in cattle, horses, sheep and swine (Package insert; Stiglyn® 1:500 – P/M; Mallinckrodt). It has also been used in the diagnosis and treatment of myasthenia gravis and in treating non-depolarizing neuromus­cular blocking agents (curare-type) overdoses in dogs.


Pharmacokinetics – Information on the pharmacokinetics of neostigmine in veterinary species was not located. In humans, neostigmine bromide is poorly absorbed after oral administration with only 1-2% of the dose absorbed. Neostigmine effects on peristaltic ac­tivity  in humans begin within 10-30 minutes after parenteral administration and can per­sist for up to 4 hours.


Neostigmine is 15-25% bound to plasma proteins. It has not been detected in human milk nor would be expected to cross the placenta when given at usual doses.


In humans, the half-life of the drug is approximately one hour. It is metabolized in the liver and also hydrolyzed by cholinesterases to 3-OH PTM which is weakly active. When administered parenterally, approximately 80% of the drug is excreted in the urine within 24 hours, with 50% excreted unchanged.


Contraindications/Precautions – Neostigmine is contraindicated in patients with peritoni­tis, mechanical intestinal or urinary tract obstructions, late stages of pregnancy, in animals hypersensitive to this class of compounds or treated with other cholinesterase inhibitors.


Use neostigmine with caution in patients with epilepsy, peptic ulcer disease, bronchial asthma, cardiac arrhythmias, hyperthyroidism, vagotonia or megacolon.


Adverse Effects/Warnings – Adverse effects of neostigmine are dose-related and cholin­ergic in nature. See overdosage section below.


Overdosage – Overdosage of neostigmine can induce a cholinergic crisis. Symptoms can include nausea, vomiting, diarrhea, excessive salivation and drooling, sweating (in animals with sweat glands), miosis, lacrimation, increased bronchial secretions, bradycardia or tachycardia, cardiospasm, bronchospasm, hypotension, muscle cramps and weakness, agi­tation, restlessness or paralysis. In patients with myasthenia gravis, it may be difficult to distinguish between a cholinergic crisis and myasthenic crisis. A test dose of edropho­nium, should differentiate between the two.


Cholinergic crisis is treated by temporarily ceasing neostigmine therapy and instituting treatment with atropine (doses are listed in the Atropine monograph). Maintain adequate respirations using mechanical assistance if necessary.


Drug Interactions – Anticholinesterase therapy may be antagonized by administration of parenteral magnesiumtherapy, as it can have a direct depressant effect on skeletal muscle.

Drugs that possess some neuromuscular blocking activity (e.g., aminoglycoside an­tibiotics, some antiarrhythmic and anesthetic drugs) may necessitate increased dosages of neostigmine in treating or diagnosing myasthenic patients. Corticosteroids may decrease the anticholinesterase activity of neostigmine. After stop­ping corticosteroid therapy, neostigmine may cause increased anticholinesterase activity. Neostigmine may prolong the Phase I block of depolarizing muscle relaxants (e.g., succinylcholine, decamethonium). Neostigmine antagonizes the actions of non-depolariz­ing neuromuscular blocking agents (pancuronium, tubocurarine, gallamine, etc.). Atropine will antagonize the muscarinic effects of neostigmine and is often used to re­duce neostigmine’s side effects. Use cautiously however, as atropine can mask the early symptoms of cholinergic crisis. Theoretically, dexpanthenol may have additive effects when used with neostigmine.


Doses –



a)   1 mg/100 lbs of body weight SQ; repeat as indicated (Package Insert; Stiglyn® 1:500 – P/M; Mallinckrodt)


For treatment of paralytic ileus of large colon:

a)   2 – 4 mg SQ q2h. Use after correction of large bowel displacement; discontinue when GI motility returns. May cause increased secretion into GI tract and there­fore may be harmful in small intestinal disease. Does not produce progressive contractions of small intestine. (Stover 1987)

b)   0.02 mg/kg SQ; duration of action may be very short (15-30 minutes); does not increase propulsive motility of jejunum and may delay gastric emptying time. (Clark and Becht 1987)



a) 4-5 mg/animal IM as a purgative in impactions; author’s clinical experience (Cheeran, 1995).


Elephant References:

a) Cheeran,J.V., Chandrasekharan,K., and Radhakrishnan,K., 1995. Principles and Practice of Fixing Dose of Drugs for Elephants. In: Daniel,J.C. (Editor), A Week with Elephants; Proceedings of the International Seminar on Asian Elephants. Bombay Natural History Society; Oxford University Press, Bombay, India pp. 430-438


Monitoring Parameters – Dependent on reason for use.

1)   Adverse reactions (see Adverse Reactions and Overdosage above)

2)   Clinical efficacy


Client Information – This product should be used by professionals in situations where the drug’s effects can be monitored.


Dosage Forms/Preparations/FDA Approval Status/Withholding Times –


Veterinary-Approved Products: None


Human-Approved Products:

Neostigmine Tablets 15 mg; Prostigmin®  (ICN); (Rx)


Neostigmine Methylsulfate Injection 1:1000 (1 mg/ml), 1:2000 (0.5 mg/ml), 1:4000 (0.25 mg/ml) in 1 ml amps and 10 ml vials; Prostigmin® (ICN); Generic; (Rx)