HIGHLIGHTS OF PRESCRIBING INFORMATION --------------------- DOSAGE FORMS AND STRENGTHS---------------------­

These highlights do not include all the information needed to use • 0.05 mg/mL injection in Ansyr™ Plastic Syringe (3)
ATROPINE SULFATE INJECTION safely and effectively. See full • 0.1 mg/mL injection in Ansyr™ Plastic Syringe (3)
prescribing information for ATROPINE SULFATE INJECTION.
------------------------------ CONTRAINDICATIONS -----------------------------­
ATROPINE SULFATE injection, for intravenous, intramuscular, None. (4)
subcuatenous or endotracheal use. ----------------------- WARNINGS AND PRECAUTIONS ----------------------­
Initial U.S. Approval: 1960
Tachycardia (5.1)
--------------------------- INDICATIONS AND USAGE---------------------------­ Glaucoma (5.2)
Atropine is a muscarinic antagonist indicated for temporary blockade of Pyloric obstruction (5.3)
severe or life threatening muscarinic effects. (1) Worsening urinary retention (5.4)
Viscid bronchial plugs (5.5)
-----------------------DOSAGE AND ADMINISTRATION ----------------------­
------------------------------ ADVERSE REACTIONS -----------------------------­
• For intravenous administration, but may also be administered via
subcutaneous, intramuscular or via an endotracheal tube (2.1, 2.3). Most adverse reactions are directly related atropine’s antimuscarinic action.
Dryness of the mouth, blurred vision, photophobia and tachycardia commonly
• Titrate according to heart rate, PR interval, blood pressure and
occur with chronic administration of therapeutic doses. (6)
symptoms. (2.1)
• Adult dosage
To report SUSPECTED ADVERSE REACTIONS, contact Hospira, Inc.
- Antisialagogue or for antivagal effects: Initial single dose of
at 1-800-441-4100 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
0.5 mg to 1 mg. (2.2)
- Antidote for organophosporous or muscarinic mushroom ------------------------------ DRUG INTERACTIONS-------------------------------
poisoning: Initial single dose of 2 mg to 3 mg, repeated every 20­ Mexiletine: Decreases rate of mexiletine absorption. (7.1)
30 minutes. (2.2)
- Bradyasystolic cardiac arrest: 1 mg dose, repeated every 3-5 Revised: 10/2015
minutes if asystole persists. (2.2)
• Patients with Coronary Artery Disease: Total dose should not exceed
0.03 mg/kg to 0.04 mg/kg. (5.1)
_______________________________________________________________________________________________________________________________

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE 8 USE IN SPECIFIC POPULATIONS
2 DOSAGE AND ADMINISTRATION 8.1 Pregnancy
2.1 General Administration 8.3 Pediatric Use
2.2 Adult Dosage 8.5 Geriatric Use
2.3 Pediatric Dosage 10 OVERDOSAGE
3 DOSAGE FORMS AND STRENGTHS 11 DESCRIPTION
4 CONTRAINDICATIONS 12 CLINICAL PHARMACOLOGY
5 WARNINGS AND PRECAUTIONS 12.1 Mechanism of Action
5.1 Tachycardia 12.2 Pharmacodynamics
5.2 Acute Glaucoma 12.3 Pharmacokinetics
5.3 Pyloric Obstruction 13 NONCLINICAL TOXICOLOGY
5.4 Complete Urinary Retintion 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
5.5 Viscid Plugs 16 HOW SUPPLIED/STORAGE AND HANDLING
6 ADVERSE REACTIONS *Sections or subsections omitted from the full prescribing information are not
7 DRUG INTERACTIONS listed.
7.1 Mexiletine

__________________________________________________________________________________________

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 FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

Atropine Sulfate Injection, USP, is indicated for temporary blockade of severe or life threatening
muscarinic effects, e.g., as an antisialagogue, an antivagal agent, an antidote for
organophosphorus or muscarinic mushroom poisoning, and to treat bradyasystolic cardiac arrest.

2 DOSAGE AND ADMINISTRATION

2.1 General Administration
Parenteral drug products should be inspected visually for particulate matter and discoloration
prior to administration, whenever solution and container permit. Do not administer unless
solution is clear and seal is intact. Discard unused portion.

Intravenous administration is usually preferred, but subcutaneous, intramuscular, and

endotracheal administration are possible. For administration via an endotracheal tube, dilute 1-2
mg in no more than 10 mL of sterile water or normal saline.

Titrate based on heart rate, PR interval, blood pressure and symptoms.

2.2 Adult Dosage

Table 1: Recommended Dosage

Use Dose (adults) Repeat
Antisialagogue or 0.5 to 1 mg 1-2 hours
other antivagal
Organophosphorus or 2 to 3 mg 20-30 minutes
muscarinic mushroom
poisoning
Bradyasystolic 1 mg 3-5 minutes; 3 mg
cardiac arrest maximum total dose

2.3 Pediatric Dosage

Dosing in pediatric populations has not been well studied. Usual initial dose is 0.01 to 0.03
mg/kg.

3 DOSAGE FORMS AND STRENGTHS

Injection: 0.05 mg/mL and 0.1 mg/mL in Ansyr™ Plastic Syringes

4 CONTRAINDICATIONS
None.

5 WARNINGS AND PRECAUTIONS

5.1 Tachycardia

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 When 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.

5.2 Acute Glaucoma

Atropine may precipitate acute glaucoma.

5.3 Pyloric Obstruction

Atropine may convert partial organic pyloric stenosis into complete obstruction.

5.4 Complete Urinary Retention

Atropine may lead to complete urinary retention in patients with prostatic hypertrophy.

5.5 Viscid Plugs

Atropine may cause inspissation of bronchial secretions and formation of viscid plugs in patients
with chronic lung disease.

6 ADVERSE REACTIONS
The following adverse reactions have been identified during post-approval use of atropine
sulfate. Because these reactions are reported voluntarily from a population of uncertain size, it is
not always possible to reliably estimate their frequency or establish a causal relationship to drug
exposure.

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. Anhidrosis can
produce heat intolerance. 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.

7 DRUG INTERACTIONS
7.1 Mexiletine
Atropine Sulfate Injection 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.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy
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.

8.3 Nursing Mothers

Trace amounts of atropine was found in breast milk. The clinical impact of this is not known.

8.5 Geriatric Use

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 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.

10 OVERDOSAGE
Excessive dosing may cause palpitation, dilated pupils, difficulty in swallowing, hot dry skin,
thirst, dizziness, restlessness, tremor, fatigue and ataxia. Toxic doses lead to 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.

The fatal adult dose of atropine is not known. In pediatric populations, 10 mg or less may be
fatal.

In the event of toxic overdosage, 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.

Atropine is not removed by dialysis.

11 DESCRIPTION
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 injection.

Each milliliter (mL) contains 0.1 mg (adult strength) or 0.05 mg (pediatric strength) of atropine
sulfate monohydrate equivalent to 0.083 mg (adult strength) or 0.042 mg (pediatric strength) of
atropine, 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).

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.

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 The 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.

Atropine 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 formula:

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.

Sodium Chloride, USP is chemically designated NaCl, a white crystalline powder freely soluble
in water.

The syringe is molded from a specially formulated 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.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Atropine is an antimuscarinic agent since it antagonizes the muscarine-like actions of
acetylcholine and other choline esters.

Atropine 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 esters.

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 12.2 Pharmacodynamics
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 respiration.

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.

Atropine 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.

The 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

12.3 Pharmacokinetics
Atropine disappears rapidly from the blood following injection and is distributed throughout the
body. 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’s plasma protein binding is
about 44% and saturable in the 2-20 μg/mL concentration range. Atropine readily crosses the
placental barrier and enters the fetal circulation, but is not found in amniotic fluid. Much of the
drug is destroyed by enzymatic hydrolysis, particularly in the liver; from 13 to 50% is excreted

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 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.

Specific Populations

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. There is no gender effect on the
pharmacokinetics and pharmacodynamics (heart rate changes) of atropine.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies have not been performed to evaluate the carcinogenic or mutagenic potential of atropine
or its potential to affect fertility adversely.

16 HOW SUPPLIED/STORAGE AND HANDLING

Atropine Sulfate Injection, USP is supplied in single-dose containers as follows:

Container Concentration Fill Total NDC#
(mg/ml) Volume Atropine
Content
Ansyr™ Plastic Syringe 0.1 mg/mL (Adult) 5 mL 0.5 mg 0409-9629-05
Ansyr™ Plastic Syringe 0.1 mg/mL (Adult) 10 mL 1 mg 0409-1630-10
Ansyr™ Plastic Syringe 0.05 mg/mL (Pediatric) 5 mL 0.25 mg 0409-9630-05

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and
86°F). [See USP Controlled Room Temperature.]

Printed in USA
Hospira, Inc., Lake Forest, IL 60045 USA

Reference ID: 3840480