atropine sulfate injection, solution Hospira, Inc.
Atropine Sulfate Injection, USP
0.1 mg/mL (Adult)
0.05 mg/mL (Pediatric)
Ansyr® Plastic Syringe
Atropine Sulfate Injection, USP is a sterile,
nonpyrogenic isotonic solution of atropine sulfate monohydrate in water for
injection with sodium chloride sufficient to render the solution isotonic.
It is administered parenterally by subcutaneous, intramuscular or intravenous
Each milliliter (mL) contains atropine sulfate,
monohydrate 0.1 mg (adult strength) or 0.05 mg (pediatric strength), and
sodium chloride, 9 mg. May contain sodium hydroxide and/or sulfuric acid for
pH adjustment 0.308 mOsmol/mL (calc.). pH 4.2 (3.0 to 6.5).
solution contains no bacteriostat, antimicrobial agent or added buffer (except
for pH adjustment) and is intended for use only as a single-dose injection.
When smaller doses are required the unused portion should be discarded.
Sulfate Injection is a parenteral anticholinergic agent and muscarinic antagonist.
Sulfate, USP is chemically designated 1α H, 5α H-Tropan-3-α-ol
(±)-tropate (ester), sulfate (2:1) (salt) monohydrate, (C17H23NO3)2•
H2SO4• H2O, colorless crystals or
white crystalline powder very soluble in water. It has the following structural
Atropine, a naturally occurring
belladonna alkaloid, is a racemic mixture of equal parts of d- and 1-hyocyamine,
whose activity is due almost entirely to the levo isomer of the drug.
Chloride, USP is chemically designated NaCl, a white crystalline powder freely
soluble in water.
The syringe is molded from a speciallyformulated polypropylene. Water permeates from inside the container at an
extremely slow rate which will have an insignificant effect on solution concentration
over the expected shelf life. Solutions in contact with the plastic container
may leach out certain chemical components from the plastic in very small amounts;
however, biological testing was supportive of the safety of the syringe material.
Atropine is commonly classified as an anticholinergic or
antiparasympathetic (parasympatholytic) drug. More precisely, however, it
is termed an antimuscarinic agent since it antagonizes the muscarine-like
actions of acetyl-choline and other choline esters.
inhibits the muscarinic actions of acetylcholine on structures innervated
by postganglionic cholinergic nerves, and on smooth muscles which respond
to endogenous acetylcholine but are not so innervated. As with other antimuscarinic
agents, the major action of atropine is a competitive or surmountable antagonism
which can be overcome by increasing the concentration of acetylcholine at
receptor sites of the effector organ (e.g., by using anticholinesterase agents
which inhibit the enzymatic destruction of acetylcholine). The receptors antagonized
by atropine are the peripheral structures that are stimulated or inhibited
by muscarine (i.e., exocrine glands and smooth and cardiac muscle). Responses
to postganglionic cholinergic nerve stimulation also may be inhibited by atropine
but this occurs less readily than with responses to injected (exogenous) choline
Atropine-induced parasympathetic inhibition
may be preceded by a transient phase of stimulation, especially on the heart
where small doses first slow the rate before characteristic tachycardia develops
due to paralysis of vagal control. Atropine exerts a more potent and prolonged
effect on heart, intestine and bronchial muscle than scopolamine, but its
action on the iris, ciliary body and certain secretory glands is weaker than
that of scopolamine. Unlike the latter, atropine in clinical doses does not
depress the central nervous system but may stimulate the medulla and higher
cerebral centers. Although mild vagal excitation occurs, the increased respiratory
rate and (sometimes) increased depth of respiration produced by atropine are
more probably the result of bronchiolar dilatation. Accordingly, atropine
is an unreliable respiratory stimulant and large or repeated doses may depress
Adequate doses of atropine abolish various
types of reflex vagal cardiac slowing or asystole. The drug also prevents
or abolishes bradycardia or asystole produced by injection of choline esters,
anticholinesterase agents or other parasympathomimetic drugs, and cardiac
arrest produced by stimulation of the vagus. Atropine also may lessen the
degree of partial heart block when vagal activity is an etiologic factor.
In some patients with complete heart block, the idioventricular rate may be
accelerated by atropine; in others, the rate is stabilized. Occasionally a
large dose may cause atrioventricular (A-V) block and nodal rhythm.
Sulfate Injection, USP in clinical doses counteracts the peripheral dilatation
and abrupt decrease in blood pressure produced by choline esters. However,
when given by itself, atropine does not exert a striking or uniform effect
on blood vessels or blood pressure. Systemic doses slightly raise systolic
and lower diastolic pressures and can produce significant postural hypotension.
Such doses also slightly increase cardiac output and decrease central venous
pressure. Occasionally, therapeutic doses dilate cutaneous blood vessels,
particularly in the “blush” area (atropine flush), and may cause
atropine “fever” due to suppression of sweat gland activity
in infants and small children.
Atropine disappears rapidly
from the blood following injection and is distributed throughout the body.
Much of the drug is destroyed by enzymatic hydrolysis, particularly in the
liver; from 13 to 50% is excreted unchanged in the urine. Traces are found
in various secretions, including milk. The major metabolites of atropine are
noratropine, atropin-n-oxide, tropine, and tropic acid. The metabolism of
atropine is inhibited by organophosphate pesticides (e.g., diazon). Atropine
readily crosses the placental barrier and enters the fetal circulation, but
is not found in amniotic fluid. Exercise, both prior to and immediately following
intramuscular administration of atropine, significantly increases the absorption
of atropine due to increased perfusion in the muscle and significantly decreases
the clearance of atropine. The pharmacokinetics of atropine is nonlinear after
intravenous administration of 0.5 to 4 mg. Atropine binds poorly (about 44%)
to plasma protein, mainly to alpha-1 acid glycoprotein; age has no effect
on the serum protein binding of atropine. Atropine binding to α-1 acid
glycoprotein was concentration-dependent (2-20 μg/mL) and nonlinear in vitro and in
vivo. The elimination half-life of atropine is more than doubled
in children under two years and the elderly (>65 years old) compared to other
age groups (2-64 years old). There is no gender effect on the pharmacokinetics
and pharmacodynamics (heart rate changes) of atropine.
effects of intravenous atropine on heart rate (maximum heart rate) and saliva
flow (minimum flow) after I.V. administration (rapid, constant infusion over
3 min.) are delayed by 7 to 8 minutes after drug administration and both effects
are non-linearly related to the amount of drug in the peripheral compartment.
Changes in plasma atropine levels following intramuscular administration (0.5
to 4 mg doses) and heart rate are closely overlapped but the time course of
the changes in atropine levels and behavioral impairment indicates that pharmacokinetics
is not the primary rate-limiting mechanism for the central nervous system
effect of atropine.
Sodium chloride added to render
the solution isotonic for injection of the active ingredient is present in
amounts insufficient to affect serum electrolyte balance of sodium (Na+)
and chloride (Cl¯) ions.
INDICATIONS AND USAGE
Atropine Sulfate Injection, USP, is indicated when excessive
(or sometimes normal) muscarinic effects are judged to be life threatening
or are producing symptoms severe enough to call for temporary, reversible
muscarinic blockade. Examples, not an exhaustive list, of such possible uses
are: (1) as an antisialoagogue when reduction of secretions of the respiratory
tract are thought to be needed; its routine use as a preanesthetic agent is
discouraged, (2) to blunt the increased vagal tone (decreased pulse and blood
pressure) produced by intra-abdominal traction or ocular muscle traction,
its routine use to prevent such events is discouraged, (3) to temporarily
increase heart rate or decrease AV-block until definitive intervention can
take place, when bradycardias or AV-block are judged to be hemodynamically
significant and thought to be due to excess vagal tone, (4) as an antidote
for inadvertent overdose of cholinergic drugs or for cholinesterase poisoning
such as from organophosphorus insecticides, (5) as an antidote for the “rapid”
type of mushroom poisoning due to the presence of the alkaloid, muscarine,
in certain species of fungus such as Amanita muscaria, and (6) to alleviate
the muscarinic side effects of anticholinesterase drugs used for reversal
of neuromuscular blockade.
Atropine generally is contraindicated in patients with glaucoma,
pyloric stenosis or prostatic hypertrophy, except in doses ordinarily used
for preanesthetic medication.
Atropine is a highly potent drug and due care is essential
to avoid overdosage, especially with intravenous administration. Pediatric
populations are more susceptible than adults to the toxic effects of anticholinergic
Atropine I.V. decreased the rate of mexiletine
absorption without altering the relative oral bioavailability; this delay
in mexiletine absorption was reversed by the combination of atropine and intravenous
metoclopramide during pretreatment for anesthesia. Atropine is not removed
Do not administer unless solution is clear and seal is intact.
Discard unused portion.
Atropine Sulfate Injection,
USP should be used with caution in all individuals over 40 years of age. Conventional
systemic doses may precipitate acute glaucoma in susceptible patients, convert
partial organic pyloric stenosis into complete obstruction, lead to complete
urinary retention in patients with prostatic hypertrophy or cause inspissation
of bronchial secretions and formation of dangerous viscid plugs in patients
with chronic lung disease.
Carcinogenesis, Mutagenesis, Impairment of Fertility:
Studies have not been performed to evaluate the carcinogenic
or mutagenic potential of atropine or its potential to adversely affect fertility.
Pregnancy Category C.
Animal reproduction studies have not been conducted with
atropine. It also is not known whether atropine can cause fetal harm when
given to a pregnant woman or can affect reproduction capacity. Atropine should
be given to a pregnant woman only if clearly needed.
Safety and effectiveness in pediatric populations have not
An evaluation of current literature revealed no clinical
experience identifying differences in response between elderly and younger
patients. In general, dose selection for an elderly patient should be cautious,
usually starting at the low end of the dosing range, reflecting the greater
frequency of decreased hepatic, renal, or cardiac function, and of concomitant
disease or other drug therapy.
Most of the side effects of atropine are directly related
to its antimuscarinic action. Dryness of the mouth, blurred vision, photophobia
and tachycardia commonly occur with chronic administration of therapeutic
doses. Anhidrosis also may occur and produce heat intolerance or impair temperature
regulation in persons living in a hot environment. Constipation and difficulty
in micturition may occur in elderly patients. Occasional hypersensitivity
reactions have been observed, especially skin rashes which in some instances
progressed to exfoliation.
Adverse effects following
single or repeated injections of atropine are most often the result of excessive
dosage. These include palpitation, dilated pupils, difficulty in swallowing,
hot dry skin, thirst, dizziness, restlessness, tremor, fatigue and ataxia.
Toxic doses lead to marked palpitation, restlessness and excitement, hallucinations,
delirium and coma. Depression and circulatory collapse occur only with severe
intoxication. In such cases, blood pressure declines and death due to respiratory
failure may ensue following paralysis and coma.
In the event of toxic overdosage (see ADVERSE REACTIONS),
a short acting barbiturate or diazepam may be given as needed to control marked
excitement and convulsions. Large doses for sedation should be avoided because
central depressant action may coincide with the depression occurring late
in atropine poisoning. Central stimulants are not recommended. Physostigmine,
given as an atropine antidote by slow intravenous injection of 1 to 4 mg (0.5
to 1 mg in pediatric populations), rapidly abolishes delirium and coma caused
by large doses of atropine. Since physostigmine is rapidly destroyed, the
patient may again lapse into coma after one to two hours, and repeated doses
may be required. Artificial respiration with oxygen may be necessary. Ice
bags and alcohol sponges help to reduce fever, especially in pediatric populations.
fatal adult dose of atropine is not known; 200 mg doses have been used and
doses as high as 1000 mg have been given.
populations, 10 mg or less may be fatal. With a dose as low as 0.5 mg, undesirable
minimal symptoms or responses of overdosage may occur. These increase in severity
and extent with larger doses of the drug (excitement, hallucinations, delirium
and coma with a dose of 10 mg or more).
DOSAGE AND ADMINISTRATION
Atropine Sulfate Injection, USP in the Ansyr Syringe is intended
for intravenous use, but may be administered subcutaneously or intramuscularly.
Its use usually requires titration, using heart rate, PR interval, blood pressure
and/or patient’s symptoms as a guide for having reached an appropriate
Initial single doses in adults vary from around
0.5 mg to 1 mg (5-10 mL of the 0.1 mg/mL solution for antisialagogue and
other antivagal effects, to 2 to 3 mg (20-30 mL) of the 0.1 mg/mL solution)
as an antidote for organophosporous or muscarinic mushroom poisoning. When
used as an antidote, the 2 to 3 mg dose should be repeated no less often than
every 20 to 30 minutes until the signs of poisoning are sufficiently lessened
or signs of atropine poisoning (see ADVERSE REACTIONS and OVERDOSAGE) occur.
the recurrent use of atropine is essential in patients with coronary artery
disease, the total dose should be restricted to 2 to 3 mg (maximum 0.03 to
0.04 mg/kg) to avoid the detrimental effects of atropine-induced tachycardia
on myocardial oxygen demand. For patients with bradyasystolic cardiac arrest,
a 1 mg dose of atropine is administered intravenously and is repeated every
3-5 minutes if asystole persists. Three milligrams (0.04 mg/kg) given I.V.
is a fully vagolytic dose in most patients. The administration of this dose
of atropine should be reserved for patients with bradyasystolic cardiac arrest.
Administration of less than 0.5 mg can produce a paradoxical bradycardia because
of the central or peripheral parasympathomimetic effects of low doses in adults.
administration of atropine can be used in patients without I.V. access. The
recommended adult dose of atropine for endotracheal administration is 1 to
2 mg diluted to a total not to exceed 10 mL of sterile water or normal saline.
intervals of one or two hours are recommended in circumstances that are not
Dosing information in pediatric populations
has not been well studied. Usage history of initial dose has been in the range
of 0.01 to 0.03 mg/kg body weight.
products should be inspected visually for particulate matter and/or discoloration
prior to administration (see PRECAUTIONS).
Atropine Sulfate Injection, USP is supplied in single-dose
containers as follows:
Store at 25°C (77°F); excursions permitted to
15° to 30°C (59° to 86°F).