Edrophonium bromide
A white odourless crystalline powder. Soluble I in 0.5 of wa-
ter and I in 5 of alcohol; practically insoluble in chloroform
and in ether. A 10% solution in water has a.pH of 4 to 5. Pro-
tect from light.
Adverse Effects, Treatment, Precautions AND Interactions as for Prostigmine which is shown below.
PROSTIGMINE
WARNINGS
Prostigmin should be used with caution in patients with epilepsy, bronchial asthma, bradycardia, recent coronary occlusion, vagotonia, hyperthyroidism, cardiac arrhythmias or peptic ulcer. When large doses of Prostigmin are administered, the prior or simultaneous injection of atropine sulfate may be advisable. Separate syringes should be used for the Prostigmin and atropine. Because of the possibility of hypersensitivity in an occasional patient, atropine and antishock medication should always be readily available.
PRECAUTIONS
General: It is important to differentiate between myasthenic crisis and cholinergic crisis caused by overdosage of Prostigmin. Both conditions result in extreme muscle weakness but require radically different treatment. (See OVERDOSAGE section.)
Drug Interactions: Prostigmin does not antagonize, and may in fact prolong, the Phase I block of depolarizing muscle relaxants such as succinylcholine or decamethonium. Certain antibiotics, especially neomycin, streptomycin and kanamycin, have a mild but definite nondepolarizing blocking action which may accentuate neuromuscular block. These antibiotics should be used in the myasthenic patient only where definitely indicated, and then careful adjustment should be made of the anticholinesterase dosage. Local and some general anesthetics, antiarrhythmic agents and other drugs that interfere with neuromuscular transmission should be used cautiously, if at all, in patients with myasthenia gravis; the dose of Prostigmin may have to be increased accordingly.
Carcinogenesis, Mutagenesis and Impairment of Fertility: There have been no studies with Prostigmin which would permit an evaluation of its carcinogenic or mutagenic potential. Studies on the effect of Prostigmin on fertility and reproduction have not been performed.
Pregnancy
Teratogenic Effects: Pregnancy Category C. There are no adequate or well-controlled studies of Prostigmin in either laboratory animals or in pregnant women. It is not known whether Prostigmin can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Prostigmin should be given to a pregnant woman only if clearly needed.
Nonteratogenic Effects: Anticholinesterase drugs may cause uterine irritability and induce premature labor when given intravenously to pregnant women near term.
Nursing Mothers: It is not known whether Prostigmin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions from Prostigmin in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use: Safety and effectiveness in children have not been established.
ADVERSE REACTIONS
Side effects are generally due to an exaggeration of pharmacological effects of which salivation and fasciculation are the most common. Bowel cramps and diarrhea may also occur.
The following additional adverse reactions have been reported following the use of either neostigmine bromide or neostigmine methylsulfate:
Allergic: Allergic reactions and anaphylaxis.
Neurologic: Dizziness, convulsions, loss of consciousness, drowsiness, headache, dysarthria, miosis and visual changes.
Cardiovascular: Cardiac arrhythmias (including bradycardia, tachycardia, A-V block and nodal rhythm) and nonspecific EKG changes have been reported, as well as cardiac arrest, syncope and hypotension. These have been predominantly noted following the use of the injectable form of Prostigmin.
Respiratory: Increased oral, pharyngeal and bronchial secretions, dyspnea, respiratory depression, respiratory arrest and bronchospasm.
Dermatologic: Rash and urticaria.
Gastrointestinal: Nausea, emesis, flatulence and increased peristalsis.
Genitourinary: Urinary frequency.
Musculoskeletal: Muscle cramps and spasms, arthralgia.
Miscellaneous: Diaphoresis, flushing and weakness.
Uses and Administration
Edrophonium is a quaternary ammonium compound
which is a reversible inhibitor of cholinesterase ac-
tivity. It has actions similar to those of neostigmine,
but its effect on skeletal muscle is claimed
to be particularly prominent. Its action is rapid in
onset and of short duration. In patients with
myasthenia gravis, there is immediate subjective im-
provement and muscle strength increases. This ef-
fect usually lasts only for about 5 to 15 minutes,
after which time the typical signs and symptoms re-
turn: because of its brief action the drug is not suit-
able for the routine treatment of myasthenia gravis.
Edrophonium chloride is used in myasthenia
gravis both diagnostically and to distin-
guish between its under- or over-treatment with oth-
er anticholinesterases. The usual diagnostic
procedure is to inject 2 mg intravenously and, if no
adverse reaction occurs within 30 to 45 seconds, to
continue with the injection of a further 8 mg. In the
UK the recommended total dose for children is
I (X) ng per kg body-weight, one-fifth of the dose be-
ing given initially, followed 30 seconds later by the
remainder if no adverse effect develops. In the USA
the manufacturers suggest a total dose of 5 mg for
children weighing less than 34 kg and 10 mg for
heavier children with one-fifth of the dose being giv-
en initially followed by increments of I mg every 30
to 45 seconds: the suggested total dose for infants is
0.5 mg. When intravenous injection is difficult edro-
phonium may be given by intramuscular injection,
the usual dose in adults is 10 mg while children be-
low 34 kg in weight may be given 2 mg and heavier
children 5 mg: infants may be given 0.5 to I mg in-
tramuscularly or subcutaneously. Atropine should
always be available when the test is carried out in
order to treat any severe muscarinic reactions that
may occur.
To detect under- or over-treatment, test doses of I to
2 mg of edrophonium chloride are given intrave-
nously to distinguish severe symptoms of myasthe-
nia gravis due to inadequate therapy, from the
effects of overdosage with anticholinesterase drugs.
If treatment has been inadequate, edrophonium
chloride will produce an immediate amelioration of
symptoms, whereas in cholinergic crises due lo
over-treatment the symptoms will be temporarily
aggravated. The manufacturers suggest administra-
tion one hour after the last dose of treatment but oth-
er authorities recommend administration just before
the next dose is due. It is advised that testing should
only be undertaken when facilities for endotracheal
intubation and controlled ventilation are immediate-
ly available.
Edrophonium chloride was originally introduced for
the reversal of neuromuscular blockade in anaes-
thesia. In the UK the recommended dose for the re-
versal of the effects of competitive neuromuscular
blockers is 500 to 700 ng per kg body-weight given
by intravenous injection over several minutes either
with or after atropine sulphate 0.6 mg; in the USA a
dose of 10 mg of edrophonium chloride is given
over 30 o $ seconds and repeated as required up to
a maximum of 40 mg. The brevity of its action lim-
its its value. Where prolonged apnoea occurs in a
patient treated with a depolarising neuromuscular
blocker. such' as suxamethonium, edrophonium
10 mg may be given intravenously with atropine to
determine the presence of phase II block.
Edrophonium bromide has been used similarly to
edrophonium chloride.
Reversal of neuromuscular blockade. For a discussion
of whether edrophonium might be more suitable than neostig-
mine for reversal of residual block after the use of the shorter-
acting competitive neuromuscular blockers, see under Uses
and Administration of Neostigmine.
Snake bite. For the use of anticholinesterases m the treat-
ment of snake-bite, see under Uses and Administration of Ne-
ostigmine.
Tetrodotoxin poisoning. Management of poisoning due to
tetrodotoxin, a heat stable neuromuscular blocking toxin
found in various marine animals, such as puffer fish, is mainly
symptomatic and supportive. Reports" on the effectiveness
of intravenous anticholinesterases such as edrophonium or
neostigmine in reversing muscle weakness in tetrodotoxin
poisoning have been conflicting. Although it appears that an-
ticholinesterases may only be effective during partial block
produced by tetrodotoxin some consider that, as there is no
specific antidote, any measure that brings about improvement
may be tried.