1.1 Mydriasis

1.2 Cycloplegia

1.3 Penalization of the healthy eye in the treatment of amblyopia

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.

5.1 Photophobia and Blurred Vision

Photophobia and blurred vision due to pupil unresponsiveness and cycloplegia may last up to 2 weeks.

5.2 Elevation of Blood Pressure

Elevation in blood pressure from systemic absorption has been reported following conjunctival instillation of recommended doses of atropine sulfate ophthalmic solution, 1%.

5.3 Increased Adverse Drug Reaction Susceptibility with Certain Central Nervous System Conditions

Individuals with Down syndrome, spastic paralysis, or brain damage are particularly susceptible to central nervous system disturbances, cardiopulmonary, and gastrointestinal toxicity from systemic absorption of atropine.

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.

7.1 Monoamine Oxidase Inhibitors

The use of atropine and monoamine oxidase inhibitors (MAOI) is generally not recommended because of the potential to precipitate hypertensive crisis.

8.1 Pregnancy

Risk Summary

There are no adequate and well-controlled studies with atropine sulfate ophthalmic solution 1% 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

There is no information to inform risk regarding the presence of atropine in human milk following ocular administration of atropine sulfate ophthalmic solution 1% 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 ophthalmic solution 1% and any potential adverse effects on the breastfed child from atropine sulfate ophthalmic solution 1%.

8.4 Pediatric Use

Due to the potential for systemic absorption of atropine sulfate ophthalmic solution the use of atropine sulfate ophthalmic solution 1% in children under the age of 3 months is not recommended and the use in children under 3 years of age should be limited to no more than one drop per eye per day. Safety and efficacy in children above the age of 3 months has been established in adequate and well controlled trials.

8.5 Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and adult patients.

12.1 Mechanism of Action

Atropine acts as a competitive antagonist of the parasympathetic (and sympathetic) acetylcholine muscarinic receptors. Topical atropine on the eye induces mydriasis by inhibiting contraction of the circular pupillary sphincter muscle normally stimulated by acetylcholine. This inhibition allows the countering radial pupillary dilator muscle to contract which results in dilation of the pupil. Additionally, atropine induces cycloplegia by paralysis of the ciliary muscle which controls accommodation while viewing objects.

12.2 Pharmacodynamics

The onset of action after administration of atropine sulfate ophthalmic solution 1% generally occurs in minutes with maximal effect seen in hours and the effect can last multiple days [see Clinical Studies (14)].

12.3 Pharmacokinetics

In a study of healthy subjects, after topical ocular administration of 30 µL of atropine sulfate ophthalmic solution, 1%, the mean (± SD) systemic bioavailability of l-hyoscyamine was reported to be approximately 64 ± 29% (range 19% to 95%) as compared to intravenous administration of atropine sulfate. The mean (± SD) time to maximum plasma concentration (Tmax) was approximately 28 ± 27 minutes (range 3 to 60 minutes), and the mean (±SD) peak plasma concentration (Cmax) of l-hyoscyamine was 288 ± 73 pg/mL. The mean (±SD) plasma half-life was reported to be approximately 2.5 ± 0.8 hours.

In a separate study of patients undergoing ocular surgery, after topical ocular administration of 40 µL of atropine sulfate ophthalmic solution, 1%, the mean (± SD) plasma Cmax of l-hyoscyamine was 860 ± 402 pg/mL.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Atropine sulfate was negative in the Salmonella/microsome mutagenicity test. Studies to evaluate carcinogenicity and impairment of fertility have not been conducted.