ATROPINE SULFATE injection, solution

1. No Title 1572550798
2. No Title 1572551578
3. No Title 1572450391
4. Description
5. Clinical Pharmacology
6. Indications And Usage
7. Contraindications
8. Warnings
9. Adverse Reactions
10. Overdosage
11. Dosage And Administration
12. How Supplied
13. Storage
14. Atropine Sulfate
15. Atropine Sulfate
16. Description
17. Clinical Pharmacology
18. Indications And Usage
19. Contraindications
20. Warnings
21. Precautions
22. Adverse Reactions
23. Overdosage
24. Dosage And Administration
25. How Supplied
26. Principal Display Panel
27. Highlights Of Prescribing Information
28. Dosage Forms And Strengths
29. Warnings And Precautions
30. Drug Interactions
31. 1 Indications And Usage
32. 2 Dosage And Administration
33. 3 Dosage Forms And Strengths
34. 4 Contraindications
35. 5 Warnings And Precautions
36. 6 Adverse Reactions
37. 7 Drug Interactions
38. 8 Use In Specific Populations
39. 10 Overdosage
40. 11 Description
41. 12 Clinical Pharmacology
42. 13 Nonclinical Toxicology
43. 16 How Supplied/storage And Handling
44. 1 Indications And Usage
45. 2 Dosage And Administration
46. 3 Dosage Forms And Strengths
47. No Title 1572456033
48. Package Label.principal Display Panel
49. Serialization Label - 1010-25

No Title 1572550798 ⮝

Rx Only

(pH 3.0 - 6.5)

No Title 1572551578 ⮝

Rx Only

(pH 3.0 - 6.5)

No Title 1572450391 ⮝

Rx Only

(pH 3.0 - 6.5)

Description  ⮝

Atropine Sulfate Injection, USP is a sterile, isotonic solution of Atropine Sulfate in Water for Injection q.s. Sodium Chloride added for isotonicity. pH adjusted with Sulfuric Acid. Preservative free.

Atropine is a white crystalline alkaloid which may be extracted from belladonna root and hyoscyamine or may be produced synthetically. It is used in the form of atropine sulfate because this compound has much greater solubility in water. The structural formula of Atropine is as follows:

Clinical Pharmacology  ⮝

Atropine has two actions. The most important therapeutic action is the inhibition of smooth muscle and glands innervated by postganglionic cholinergic nerves. Atropine also has central-nervous system activity, which may be stimulating or depressing depending upon the dose.

Indications And Usage  ⮝

1. In the treatment of parkinsonism. Rigidity and tremor relieved by the apparently selective depressant action.
2. In the gastrointestinal tract to relieve pylorospasm, hypertonicity of the small intestine and the hypermotility of the colon.
3. To relieve hypertonicity of the uterine muscle.
4. To relax the spasm of biliary and uretered colic and bronchial spasm.
5. To diminish the tone of the detrusor muscle of the urinary bladder in the treatment of urinary tract disorders.
6. To control the crying and laughing episodes in patients with brain lesions.
7. In cases of closed head injuries which cause acetylcholine to be released or to be present in cerebrospinal fluid which in turn causes abnormal EEG patterns, stupor and neurological signs.
8. In the management of peptic ulcer.
9. In anesthesia to control excessive salivation and bronchial secretions.
10. To control rhinorrhea of acute rhinitis or hay fever.
11. As an antidote for pilocarpine, physostigmine, isoflurophate, choline esters, certain species of Aminata and in cases of anticholinesterase insecticide poisoning.
12. In poisoning by the organic phosphate cholinesterase inhibitors found in certain insecticides and by chemical warfare nerve gases , large doses of atropine relieve the muscarine-like symptoms and some of the central-nervous-system manifestations. Adults suspected of contact with organic phosphorus insecticides of the parathion type should be given atropine sulfate, 0.8 mg, intramuscularly. If an atropine effect is not apparent within thirty minutes or if definite symptoms of the poisoning occur (nausea, vomiting, diarrhea, pupillary constriction, pulmonary edema, fasciculations of eyelids and tongue, jerky ocular movements, and excessive sweating, salivation, and bronchial secretion), atropine sulfate, 2 mg, should be given intramuscularly at hourly intervals until signs of atropinization are observed. Up to two or three times this dose (4 to 6 mg) may be required in severe cases. Removing contaminated clothing, washing the skin, and commencing artificial respiration and supportive therapy are also indicated.

Contraindications  ⮝

Conditions in which inhibition of postganglionic cholinergic nerves are undesirable, such as glaucoma and tachycardia. Also contraindicated in asthma, because the parenteral dose which might relieve asthma would have an excessive drying effect upon mucous plugs in the bronchi. Prostatic hypertrophy, while not a contraindication, requires special attention to signs of urinary retention.

Warnings  ⮝

Doses of 0.5 to 1 mg of atropine are mildly stimulating to the central nervous system. Larger doses may produce mental disturbances; still larger doses are depressing. Death from atropine poisoning, though rare, is usually due to paralysis of the medullary centers.

Pregnancy

Teratogenic Effects

Pregnancy Category B. Reproduction studies have been performed in mice in doses of 50 mg/kg of body weight and have revealed no evidence of impaired fertility or harm to the fetus due to Atropine Sulfate. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Adverse Reactions  ⮝

Toxic effects from overdosage of atropine are not uncommon, especially in children. Individual tolerance varies greatly, but these systemic doses are likely to produce the following effects.

0.5 mg	Slight dryness of nose and mouth; bradycardia.
1 mg	Greater dryness of nose and mouth, with thirst; slowing then acceleration of heart; slight mydriasis.
2 mg	Very dry mouth; tachycardia with palpitation, mydriasis, slight blurring of near vision; flushed, dry skin.
5 mg	Increase in above symptoms plus disturbance of speech; difficulty in swallowing; headache, hot, dry skin; restlessness, with asthenia.
10 mg and over	Above symptoms to extreme degree, plus ataxia, excitement, disorientation, hallucinations, delirium, and coma.
65 mg	May be fatal.

A scarlatiniform rash may occur. Atropine may produce fever, particularly in children, through inhibition of heat loss by evaporation. Although large doses of atropine may cause an alarming condition, recovery is usual.

In the treatment of atropine poisoning, respiratory assistance and symptomatic support are indicated.

Pilocarpine is sometimes given but is of limited value.

Overdosage  ⮝

1. If marked excitement is present, a short acting barbiturate, chloral hydrate of paraldehyde may be used for sedation. Large doses should be avoided if possible and must be carefully controlled so that they will not add to the depressive stages of atropine poisoning.
2. Artificial respiration with oxygen is necessary when respiration is depressed.
3. Depression may be controlled by use of caffeine, sodium benzoate or picrotoxin together with the inhalation of oxygen.
4. As a physiologic antidote, neostigmine methylsulfate may be given by intramuscular injection in doses of 500 mcg to 1 mg and repeated every 2 to 9 hours.
5. Remaining therapy is purely symptomatic. Icebags and alcohol sponges help to reduce fever, especially in children. Careful nursing is essential. The room should be darkened, because of the patient s marked photophobia.

Dosage And Administration  ⮝

The usual adult dose of atropine is 0.4 to 0.6 mg. Suggested doses for children are as follows:

7 - 16 pounds	-	0.1 mg
17 - 24 pounds	-	0.15 mg
24 - 40 pounds	-	0.2 mg
40 - 65 pounds	-	0.3 mg
65 - 90 pounds	-	0.4 mg
Over 90 pounds	-	0.4 to 0.6 mg

As indicated previously, however, these doses may be considerably exceeded in certain cases.

Parenteral drug products should be inspected visually for particulate matter and discoloration, whenever solution and container permit.

How Supplied  ⮝

Product No.	Concentration	Vial/Ampule Size
NDC 0517-0805-25	0.4 mg/0.5 mL	0.5 mL Ampule packed in boxes of 25
NDC 0517-0101-25	1.0 mg/1 mL	1 mL Ampule packed in boxes of 25
NDC 0517-0401-25	0.4 mg/1 mL	1 mL Single Dose Vial packed in boxes of 25
NDC 0517-1010-25	1.0 mg/1 mL	1 mL Single Dose Vial packed in boxes of 25

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

AMERICAN
REGENT, INC.
SHIRLEY, NY 11967

IN1010
Rev. 1/09

Storage ⮝

DISCARD UNUSED PORTION. Store at 20 to 25 C (68 to 77 F); excursions permitted to 15 to 30 C (59 to 86 F) (See USP Controlled Room Temperature). AMERICAN REGENT, INC. SHIRLEY, NY 11967

Atropine Sulfate ⮝

ATROPINE SULFATE atropine sulfate injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:50090-4524(NDC:0517-1010) Route of Administration INTRAMUSCULAR, INTRAVENOUS, SUBCUTANEOUS

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ATROPINE SULFATE (UNII: 03J5ZE7KA5) (ATROPINE - UNII:7C0697DR9I) ATROPINE SULFATE 1 mg in 1 mL

Inactive Ingredients Ingredient Name Strength SODIUM CHLORIDE (UNII: 451W47IQ8X) 9 mg in 1 mL SULFURIC ACID (UNII: O40UQP6WCF) WATER (UNII: 059QF0KO0R)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:50090-4524-0 1 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product 09/13/2019

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date UNAPPROVED DRUG OTHER 12/01/1992

Labeler - A-S Medication Solutions (830016429)

Establishment
Name	Address	ID/FEI	Business Operations
A-S Medication Solutions		830016429	RELABEL(50090-4524) , REPACK(50090-4524)

Revised: 9/2019 Document Id: 7d831b5c-cc5d-480f-a8d5-e3197ead9c5c 34391-3 Set id: 085b4e3d-7211-4435-89fb-300093e0ec82 Version: 3 Effective Time: 20190918 A-S Medication Solutions

Atropine Sulfate ⮝

ATROPINE SULFATE atropine sulfate injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:50090-2181(NDC:0409-4911) Route of Administration INTRAVENOUS

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ATROPINE SULFATE (UNII: 03J5ZE7KA5) (ATROPINE - UNII:7C0697DR9I) ATROPINE SULFATE 0.1 mg in 1 mL

Inactive Ingredients Ingredient Name Strength SODIUM CHLORIDE (UNII: 451W47IQ8X) 9 mg in 1 mL SODIUM HYDROXIDE (UNII: 55X04QC32I) SULFURIC ACID (UNII: O40UQP6WCF) WATER (UNII: 059QF0KO0R)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:50090-2181-0 1 in 1 CARTON 10/26/2015 1 10 mL in 1 SYRINGE ; Type 1: Convenience Kit of Co-Package

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA021146 10/25/2005

Labeler - A-S Medication Solutions (830016429)

Establishment
Name	Address	ID/FEI	Business Operations
A-S Medication Solutions		830016429	RELABEL(50090-2181)

Revised: 1/2018 Document Id: 0ef7e127-3f97-4252-b8d1-437c72551553 34391-3 Set id: 10f4a112-9651-4ef6-8aae-6bcaaac94246 Version: 3 Effective Time: 20180109 A-S Medication Solutions

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 atropine sulfate, monohydrate 0.1 mg (adult 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).

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 Injection is a parenteral anticholinergic agent and muscarinic antagonist.

Atropine Sulfate, USP is chemically designated 1 H, 5 H-Tropan-3- 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.

Clinical Pharmacology ⮝

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.

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.

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.

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. Atropine readily crosses the placental barrier and enters the fetal circulation.

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 is a muscarinic antagonist indicated for temporary blockade of severe or life threatening muscarinic effects. (1)

Contraindications ⮝

None. (4)

Warnings ⮝

Atropine is a highly potent drug and due care is essential to avoid overdosage, especially with intravenous administration. Children are more susceptible than adults to the toxic effects of anticholinergic agents.

Precautions ⮝

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.

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.

Adverse Reactions ⮝

Most adverse reactions are directly related to atropine's antimuscarinic action. Dryness of the mouth, blurred vision, photophobia and tachycardia commonly occur with chronic administration of therapeutic doses. (6)

To report SUSPECTED ADVERSE REACTIONS, contact Hospira, Inc. at 1-800-441-4100, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Overdosage ⮝

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 1.0 mg in children), 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 children.

The fatal adult dose of atropine is not known; 200 mg doses have been used and doses as high as 1000 mg have been given.

In children, 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 ⮝

• For intravenous administration. (2.1, 2.3)
• Titrate according to heart rate, PR interval, blood pressure and symptoms. (2.1)
• Adult dosage

  -

  Antisialagogue or for antivagal effects: Initial single dose of 0.5 mg to 1 mg. (2.2)

  -

  Antidote for organophosphorus or muscarinic mushroom poisoning: Initial single dose of 2 mg to 3 mg, repeated every 20 30 minutes. (2.2)

  -

  Bradyasystolic cardiac arrest: 1 mg dose, repeated every 3 5 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)

How Supplied ⮝

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

List No.	Needle	Size	Conc.	Total Content (Atropine)
LifeShield Abboject Unit of Use Syringe with male luer lock adapter and protected needle
4910	20-G	5 mL	0.1 mg/mL (Adult)	0.5 mg
4911	20-G	10 mL	0.1 mg/mL (Adult)	1 mg

Store at 20 to 25 C (68 to 77 F). [See USP Controlled Room Temperature.]

Revised: February, 2007

Printed in USA EN-1435

Hospira, Inc., Lake Forest, IL 60045 USA

Cardinal Health

Zanesville, OH 43701

IA60031111

Principal Display Panel ⮝

Atropine Sulfate Injection,

USP 1 mg (0.1 mg/mL)

1 x 10 mL Glass Abboject

Unit of Use Syringe

ATROPINE SULFATE atropine sulfate injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:55154-6981(NDC:0409-4911) Route of Administration INTRAVENOUS, INTRAMUSCULAR, SUBCUTANEOUS

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ATROPINE SULFATE (UNII: 03J5ZE7KA5) (ATROPINE - UNII:7C0697DR9I) ATROPINE SULFATE 0.1 mg in 1 mL

Inactive Ingredients Ingredient Name Strength SODIUM CHLORIDE (UNII: 451W47IQ8X) SODIUM HYDROXIDE (UNII: 55X04QC32I) SULFURIC ACID (UNII: O40UQP6WCF)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:55154-6981-8 1 in 1 BAG 10/25/2005 10/31/2019 1 1 in 1 CARTON 1 10 mL in 1 SYRINGE; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date Unapproved drug other 10/25/2005 10/31/2019

Labeler - Cardinal Health (603638201)

Revised: 9/2019 Document Id: 98cf5fad-0261-4b8b-ab06-e7064c900599 34391-3 Set id: 910cb308-36c6-4330-8f25-45998ec3cde7 Version: 3 Effective Time: 20190913 Cardinal Health

Highlights Of Prescribing Information ⮝

These highlights do not include all the information needed to use ATROPINE SULFATE INJECTION safely and effectively. See full prescribing information for ATROPINE SULFATE INJECTION.

ATROPINE SULFATE INJECTION, for intravenous use

Initial U.S. Approval: 1960

Dosage Forms And Strengths ⮝

• 0.1 mg/mL injection in LifeShield Abboject Glass Syringe (3)

Warnings And Precautions ⮝

Tachycardia (5.1)

Glaucoma (5.2)

Pyloric obstruction (5.3)

Worsening urinary retention (5.4)

Viscid bronchial plugs (5.5)

Drug Interactions ⮝

Mexiletine: Decreases rate of mexiletine absorption. (7.1)

Revised: 1/2018

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.

For intravenous administration.

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 other antivagal	0.5 to 1 mg	1 2 hours
Organophosphorus or muscarinic mushroom poisoning	2 to 3 mg	20 30 minutes
Bradyasystolic cardiac arrest	1 mg	3 5 minutes; 3 mg 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: 0.1 mg/mL in LifeShield Abboject Glass Syringes

4 Contraindications ⮝

None.

5 Warnings And Precautions ⮝

5.1 Tachycardia

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.

8.4 Pediatric Use

Recommendations for use in pediatric patients are not based on clinical trials.

8.5 Geriatric Use

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 intravenous injection.

Each milliliter (mL) contains 0.1 mg of atropine sulfate monohydrate equivalent to 0.083 mg of atropine, and sodium chloride, 9 mg. May contain sodium hydroxide and/or sulfuric acid for pH adjustment 0.308 mOsmol/mL (calc.). pH 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.

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 1 H, 5 H-Tropan-3- -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.

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.

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 g/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 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 ⮝

Product: 50090-2181

NDC: 50090-2181-0 10 mL in a SYRINGE

LAB-0879-2.0

Hospira, Inc., Lake Forest, IL 60045 USA

1 Indications And Usage ⮝

Atropine is indicated for temporary blockade of severe or life threatening muscarinic effects, e.g., as an antisialagogue, an antivagal agent, an antidote for organophosphorus, carbamate, or muscarinic mushroom poisoning, and to treat symptomatic bradycardia.

2 Dosage And Administration ⮝

2.1 General Administration

Inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer unless solution is clear and seal is intact. After initial use, discard unused portion within 24 hours.
Intravenous administration is usually preferred, but subcutaneous, intramuscular, endotracheal, and intraosseous administration are possible.

2.2 Adult Dosage

Table 1: Recommended Dosage in Adult Patients

Use	Initial Dose	Continued Treatment
Antisialagogue or other antivagal (preanesthesia and during surgery)	0.5 to 1 mg IV/IM/SC 30-60 minutes preoperatively	Repeat as needed every 4-6 hours. Maximum Total Dose 3 mg
Organophosphorus, carbamate or muscarinic mushroom poisoning	1 to 6 mg IV/IM/ET depending on severity of symptoms	Repeat as needed every 3 to 5 minutes Dose may be doubled with each administration until response (reduced bronchospasm, improved oxygenation and drying of pulmonary secretions). Maintenance Dose: Administer 10% to 20% of the loading dose required for response as a continuous infusion per hour and titrate. Maximum Total Dose: No maximum total dose.
Symptomatic bradycardia*	0.5 mg IV/IM or 1 to 2 mg ET by diluting in no more than 10 mL sterile water for injection or 0.9% sodium chloride	As needed every 3 to 5 minutes Maximum Total Dose 3 mg
IV=intravenous; IM=intramuscular; SC=subcutaneous; ET=endotracheal *Do not rely on atropine in type II second-degree or third-degree AV block with wide QRS complexes because these bradyarrhythmias are not likely to be responsive to reversal of cholinergic effects by atropine. Atropine has no effect on bradycardia in patients with transplanted hearts.

2.3 Pediatric Dosage

Table 2: Recommended Dosage in Pediatric Patients

Use	Initial Dose	Continued Treatment
Antisialagogue or other antivagal (preanesthesia and during surgery)*	0.02 mg/kg IV/IM/SC 30-60 minutes preoperatively	Repeat as needed every 4-6 hours.
		Maximum Single Dose Less than 12 years old: 0.5 mg 12 years and older: 1 mg	Maximum Total Dose Less than 12 years old: 1 mg 12 years and older: 2 mg
Organophosphorus, carbamate, or muscarinic mushroom poisoning	0.02 to 0.06 mg/kg IV/IM/IO/ET	Repeat as needed every 5 minutes Dose may be doubled with each administration until response (reduced bronchospasm, improved oxygenation and drying of pulmonary secretions). Maintenance Dose: Administer 10% to 20% of the loading dose required for response as a continuous infusion per hour and titrate as needed. Maximum Total Dose: No maximum total dose.
Symptomatic bradycardia due to increased vagal tone or primary AV conduction block (not secondary to hypoxia) * *	0.02 mg/kg IV/IO or 0.04 to 0.06 mg/kg via endotracheal tube followed by 1 to 5 mL flush of normal saline followed by 5 ventilations	Repeat as needed every 5 minutes Maximum Single Dose Less than12 years old: 0.5 mg 12 years and older: 1 mg
IV=intravenous; IM=intramuscular; SC=subcutaneous; IO=intraosseous; ET=endotracheal; *Available evidence does not support the routine use of atropine in emergency intubation of critically ill infants and children except in specific emergency intubations when there is higher risk of bradycardia ** Atropine has no effect on bradycardia in patients with transplanted hearts.

2.4 Dosing in Patients with Ischemic Heart Disease

Limit the total dose of atropine sulfate to 0.03 to 0.04 mg/kg [see Warnings and Precautions (5.2)].

3 Dosage Forms And Strengths ⮝

Atropine Sulfate Injection, USP, 8 mg per 20 mL (0.4 mg per mL), is a non-pyrogenic, isotonic, clear solution and is supplied in a multiple dose glass vial.

No Title 1572456033 ⮝

Rx Only

(pH 3.0 - 6.5)

Package Label.principal Display Panel  ⮝

PRINCIPAL DISPLAY PANEL 1 mL Carton

ATROPINE SULFATE
INJECTION, USP
0.4 mg/mL

NDC 0517-0401-25

25 x 1 mL
SINGLE DOSE VIALS

FOR INTRAVENOUS, INTRAMUSCULAR OR SUBCUTANEOUS USE

PRESERVATIVE FREE

Rx Only

Each mL contains: Atropine Sulfate 0.4 mg, Sodium Chloride 9 mg, Water for Injection q.s. pH adjusted with Sulfuric Acid.

WARNING: DISCARD UNUSED PORTION.

Store at 20 -25 C (68 -77 F); excursions permitted to 15 -30 C (59 -86 F) (See USP Controlled Room Temperature). Directions for Use: See Package Insert.

AMERICAN REGENT, INC.
SHIRLEY, NY 11967

Rev. 11/05

PRINCIPAL DISPLAY PANEL 1 mL Carton

ATROPINE SULFATE
INJECTION, USP

1 mg/mL

NDC 0517-1010-25

25 x 1 mL
SINGLE DOSE VIALS

FOR INTRAVENOUS, INTRAMUSCULAR OR SUBCUTANEOUS USE

PRESERVATIVE FREE

Rx Only

Each mL contains: Atropine Sulfate 1 mg, Sodium Chloride 9 mg, Water for Injection q.s. pH adjusted with Sulfuric Acid.

WARNING: DISCARD UNUSED PORTION. Store at 20 to 25 C (68 to 77 F); excursions permitted to 15 to 30 C (59 to 86 F) (See USP Controlled Room Temperature). Directions for Use: See Package Insert.

AMERICAN
REGENT, INC.
SHIRLEY, NY 11967

Rev. 11/05

Serialization Label - 1010-25 ⮝

ATROPINE SULFATE atropine sulfate injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0517-1010 Route of Administration INTRAMUSCULAR, INTRAVENOUS, SUBCUTANEOUS

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ATROPINE SULFATE (UNII: 03J5ZE7KA5) (ATROPINE - UNII:7C0697DR9I) ATROPINE SULFATE 1 mg in 1 mL

Inactive Ingredients Ingredient Name Strength SODIUM CHLORIDE (UNII: 451W47IQ8X) 9 mg in 1 mL SULFURIC ACID (UNII: O40UQP6WCF) WATER (UNII: 059QF0KO0R)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0517-1010-25 25 in 1 TRAY 12/01/1992 1 1 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date UNAPPROVED DRUG OTHER 12/01/1992

ATROPINE SULFATE atropine sulfate injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0517-0401 Route of Administration INTRAMUSCULAR, INTRAVENOUS, SUBCUTANEOUS

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ATROPINE SULFATE (UNII: 03J5ZE7KA5) (ATROPINE - UNII:7C0697DR9I) ATROPINE SULFATE 0.4 mg in 1 mL

Inactive Ingredients Ingredient Name Strength SODIUM CHLORIDE (UNII: 451W47IQ8X) 9 mg in 1 mL SULFURIC ACID (UNII: O40UQP6WCF) WATER (UNII: 059QF0KO0R)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0517-0401-25 25 in 1 TRAY 11/01/1992 1 1 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date UNAPPROVED DRUG OTHER 11/01/1992

Labeler - American Regent, Inc. (622781813)

Establishment
Name	Address	ID/FEI	Business Operations
Luitpold Pharmaceuticals, Inc.		002033710	ANALYSIS(0517-1010, 0517-0401) , MANUFACTURE(0517-1010, 0517-0401) , STERILIZE(0517-1010, 0517-0401)

Revised: 12/2018 Document Id: 04647db2-a0a7-4d93-a34b-f3299aedabc0 34391-3 Set id: 78e42769-061f-4973-ac3a-dc3fcc4bf641 Version: 5 Effective Time: 20181219 American Regent, Inc.