Atropine Sulfate

1 INDICATIONS AND USAGE Atropine Sulfate Ophthalmic Solution, 1% is indicated in adults and pediatric patients aged three (3) months and older for: Atropine is an anticholinergic indicated in adults and pediatric patients aged three (3) months and older for: Cycloplegia ( 1.1 ) Mydriasis ( 1.2 ) Penalization of the healthy eye in the treatment of amblyopia ( 1.3 ) 1.1 Cycloplegia . 1.2 Mydriasis . 1.3 Penalization of the Healthy Eye in the Treatment of Amblyopia .

2 DOSAGE AND ADMINISTRATION In individuals from three (3) months of age or greater 1 drop topically to the cul-de-sac of the conjunctiva, forty minutes prior to the intended maximal dilation time (2.1) In individuals 3 years of age or greater, doses may be repeated up to twice daily as needed. (2.2) 2.1 In individuals from three (3) months of age or greater, 1 drop topically to the cul-de-sac of the conjunctiva, forty minutes prior to the intended maximal dilation time. 2.2 In individuals 3 years of age or greater, doses may be repeated up to twice daily as needed.

3 DOSAGE FORMS AND STRENGTHS Atropine Sulfate Ophthalmic Solution, USP 1%: each mL contains 10 mg of atropine sulfate equivalent to 8.3 mg of atropine Ophthalmic solution: 1% atropine sulfate

4 CONTRAINDICATIONS Hypersensitivity or allergic reaction to any ingredient in formulation (4.1) 4.1 Hypersensitivity to any Component of this Medication Atropine sulfate ophthalmic solution should not be used in anyone who has demonstrated a previous hypersensitivity or known allergic reaction to any ingredient of the formulation because it may recur.

6 ADVERSE REACTIONS The following adverse reactions are described below and elsewhere in the labeling: Photophobia and Blurred Vision [see Warnings and Precautions (5.1)] Elevation in Blood Pressure [see Warnings and Precautions (5.2)] Increased Adverse Drug Reaction Susceptibility with Certain Central Nervous System Conditions [see Warnings and Precautions (5.3)] The following adverse reactions have been identified following use of atropine sulfate ophthalmic solution. 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. The most common adverse reactions that have been reported are eye pain and stinging on administration, blurred vision, photophobia, superficial keratitis, decreased lacrimation, drowsiness, increased heart rate and blood pressure. (6) To report SUSPECTED ADVERSE REACTIONS, contact Somerset Therapeutics, LLC at 1-800-417-9175 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Ocular Adverse Reactions Eye pain and stinging occurs upon instillation of atropine sulfate ophthalmic solution. Other commonly occurring adverse reactions include blurred vision, photophobia, superficial keratitis and decreased lacrimation. Allergic reactions such as papillary conjunctivitis, contact dermatitis, and eyelid edema may also occur less commonly. 6.2 Systemic Adverse Reactions Systemic effects of atropine are related to its anti-muscarinic activity. Systemic adverse events reported include dryness of skin, mouth, and throat from decreased secretions from mucus membranes; drowsiness; restlessness, irritability or delirium from stimulation of the central nervous system; tachycardia; flushed skin of the face and neck.

7 DRUG INTERACTIONS The use of atropine and monoamine oxidase inhibitors (MAOI) is generally not recommended because of the potential to precipitate hypertensive crisis. (7) See 17 for PATIENT COUNSELING INFORMATION. 7.1 Monoamine Oxidase Inhibitors The use of atropine and monoamine oxidase inhibitors (MAOI) is generally not recommended because of the potential to precipitate hypertensive crisis.

8 USE IN SPECIFIC POPULATIONS Should only be used in pregnant women if clearly needed. ( 8.1 ) 8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of atropine sulfate administration in pregnant women to inform a drug-associated risk. Adequate animal development and reproduction studies have not been conducted with atropine sulfate. In humans, 1% atropine sulfate is systemically bioavailable following topical ocular administration [ see Clinical Pharmacology (12.3) ]. Atropine sulfate ophthalmic solution 1% should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. 8.2 Lactation Risk Summary There is no information to inform risk regarding the presence of atropine in human milk following ocular administration of atropine sulfate to the mother. The effects on breastfed infants and the effects on milk production are also unknown. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for atropine sulfate and any potential adverse effects on the breastfed child from atropine sulfate. 8.4 Pediatric Use The safety and effectiveness of atropine sulfate ophthalmic solution 1% have been established in pediatric patients aged 3 months and older. Use of atropine sulfate ophthalmic solution 1% is supported by evidence from adequate and well-controlled trials with additional safety data from published literature. Due to the potential for systemic absorption, the use of atropine sulfate ophthalmic solution 1% in pediatric patients aged 3 months to 3 years should be limited to no more than one drop per eye per day. Use in pediatric patients younger than 3 months of age is not recommended. 8.5 Geriatric Use No overall differences in safety and effectiveness have been observed between elderly and younger adult patients.

12.1 Mechanism of Action Atropine is a reversible antagonist of muscarine-like actions of acetyl-choline and is therefore classified as an antimuscarinic agent. Atropine is relatively selective for muscarinic receptors. Its potency at nicotinic receptors is much lower, and actions at non-muscarinic receptors are generally undetectable clinically. Atropine does not distinguish among the M1, M2, and M3 subgroups of muscarinic receptors. The pupillary constrictor muscle depends on muscarinic cholinoceptor activation. This activation is blocked by topical atropine resulting in unopposed sympathetic dilator activity and mydriasis. Atropine also weakens the contraction of the ciliary muscle, or cycloplegia. Cycloplegia results in loss of the ability to accommodate such that the eye cannot focus for near vision.

11 DESCRIPTION Atropine Sulfate Ophthalmic Solution, USP 1% is a sterile topical anticholinergic for ophthalmic use. The active ingredient is represented by the chemical structure: Chemical Name: Benzeneacetic acid, α-(hydroxymethyl)-, 8-methyl-8-azabicyclo[3.2.1.]oct-3-yl ester, endo –(±)-, sulfate (2:1) (salt), monohydrate. Molecular Formula: (C 17 H 23 NO 3 ) 2 H 2 SO 4 H 2 O Molecular Weight: 694.84 g/mol Atropine sulfate, USP appears as colorless, almost white to white solid. It is very soluble in water and glacial acetic acid, freely soluble in ethanol (96%) and practically insoluble in diethyl ether. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains: Active : atropine sulfate, USP 10 mg equivalent to 8.3 mg of atropine. Inactives: benzalkonium chloride 0.1 mg (0.01%), dibasic sodium phosphate anhydrous, edetate disodium dihydrate, hypromellose (2910), monobasic sodium phosphate monohydrate, hydrochloric acid and/or sodium hydroxide may be added to adjust pH (3.5 to 6.0), and water for injection USP. structure

10 OVERDOSAGE In the event of accidental ingestion or toxic overdosage with atropine sulfate ophthalmic solution, supportive care may include a short acting barbiturate or diazepam 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 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. Cooling measures may be needed to help to reduce fever, especially in pediatric populations. The fatal adult dose of atropine is not known. In pediatric populations, 10 mg or less may be fatal.

16 HOW SUPPLIED/STORAGE AND HANDLING Atropine Sulfate Ophthalmic Solution, USP 1% is supplied as clear, colorless solution in a three piece white bottle with a natural nozzle and red cap in the following sizes: NDC 70756-651-25 2 mL fill in 5 mL bottle NDC 70756-652-25 5 mL fill in 5 mL bottle NDC 70756-653-35 15 mL fill in 15 mL bottle Storage: Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Keep container tightly closed. After opening, Atropine Sulfate Ophthalmic Solution can be used until the expiration date on the bottle.