Proparacaine Hydrochloride

INDICATIONS AND USAGE Proparacaine hydrochloride ophthalmic solution is indicated for topical anesthesia in ophthalmic practice. Representative ophthalmic procedures in which the preparation provides good local anesthesia include measurement of intraocular pressure (tonometry), removal of foreign bodies and sutures from the cornea, conjunctival scraping in diagnosis and gonioscopic examination; it is also indicated for use as a topical anesthetic prior to surgical operations such as cataract extraction.

DOSAGE AND ADMINISTRATION Usual Dosage: Removal of foreign bodies and sutures, and for tonometry: 1 to 2 drops (in single instillations) in each eye before operating. Short corneal and conjunctival procedures: 1 drop in each eye every 5 to 10 minutes for 5 to 7 doses. NOTE: Proparacaine hydrochloride ophthalmic solution USP, 0.5% should be clear, colorless to faint yellow color. If the solution becomes darker, discard the solution. FOR TOPICAL OPHTHALMIC USE ONLY

WARNINGS: NOT FOR INJECTION - FOR TOPICAL OPHTHALMIC USE ONLY. Prolonged use of a topical ocular anesthetic is not recommended. It may produce permanent corneal opacification with accompanying visual loss. ALCAINE™ ophthalmic solution is indicated for administration under the direct supervision of a healthcare provider. ALCAINE™ ophthalmic solution is not intended for patient self-administration.

CONTRAINDICATIONS Proparacaine hydrochloride ophthalmic solution should be considered contraindicated in patients with known hypersensitivity to any of the ingredients of this preparation.

ADVERSE REACTIONS Pupillary dilation or cycloplegic effects have rarely been observed with proparacaine hydrochloride. The drug appears to be safe for use in patients sensitive to other local anesthetics, but local or systemic sensitivity occasionally occurs. Instillation of proparacaine in the eye at recommended concentration and dosage usually produces little or no initial irritation, stinging, burning, conjunctival redness, lacrimation or increased winking. However, some local irritation and stinging may occur several hours after the instillation. Rarely, a severe, immediate-type, apparently hyperallergic corneal reaction may occur which includes acute, intense and diffuse epithelial keratitis; a gray, ground glass appearance; sloughing of large areas of necrotic epithelium; corneal filaments and, sometimes, iritis with descemetitis. Allergic contact dermatitis with drying and fissuring of the fingertips has been reported. Softening and erosion of the corneal epithelium and conjunctival congestion and hemorrhage have been reported. 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

CLINICAL PHARMACOLOGY Proparacaine hydrochloride ophthalmic solution is a rapid acting local anesthetic suitable for ophthalmic use. With a single drop, the onset of anesthesia occurs in approximately 13 seconds and persists for 15 minutes or longer. The main site of anesthetic action is the nerve cell membrane where proparacaine interferes with the large transient increase in the membrane permeability to sodium ions that is normally produced by a slight depolarization of the membrane. As the anesthetic action progressively develops in a nerve, the threshold for electrical stimulation gradually increases and the safety factor for conduction decreases; when this action is sufficiently well developed, block of conduction is produced. The exact mechanism whereby proparacaine and other local anesthetics influence the permeability of the cell membrane is unknown; however, several studies indicate that local anesthetics may limit sodium ion permeability by closing the pores through which the ions migrate in the lipid layer of the nerve cell membrane. This limitation prevents the fundamental change necessary for the generation of the action potential.