Atropine Sulfate

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

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

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.

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.

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.

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

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.

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%.

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.

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

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.

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)].

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 (T_max) was approximately 28 ± 27 minutes (range 3 to 60 minutes), and the mean (±SD) peak plasma concentration (C_max) 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 C_max of l-hyoscyamine was 860 ± 402 pg/mL.

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