GENERAL INFORMATION PHARMACOLOGY CLINICAL TRIALS SAFETY/COMFORT GENERAL INFORMATION What is ELESTAT®? ELESTAT® (epinastine HCl ophthalmic solution) 0.05% is an effective anti-allergy therapy that is indicated for the prevention of itching associated with allergic conjunctivitis. An antihistamine with mast cell-stabilizing activity, ELESTAT® soothes the eyes with fast-acting and sustained relief of ocular itching, the symptom allergy sufferers complain about most. How does ELESTAT® work? ELESTAT® rapidly relieves ocular itching by blocking the H1- and H2-receptors, stabilizing mast cells, and stopping the progression of proinflammatory mediators. In fact, only ELESTAT® ophthalmic solution labeling cites the prevention of histamine binding to both the H1- and H2- receptors. What is the indication for ELESTAT®? ELESTAT® ophthalmic solution is indicated for the prevention of itching associated with allergic conjunctivitis. Why should I prescribe ELESTAT® for ocular itching? You should prescribe ELESTAT® ophthalmic solution because it has a fast onset of action that provides significant ocular itching reduction within 3 minutes and a sustained effect that lasts for up to 12 hours. ELESTAT® is effective at inhibiting degranulation of mast cells, and has been shown to effectively reduce ocular itching due to allergic conjunctivitis. Does ELESTAT® burn and sting upon instillation? ELESTAT® is soothing to the eyes upon instillation. It has a pH of 7.0, which is similar to natural tears. There is a low potential for ocular surface drying, and ELESTAT® is very well tolerated by patients who have used it. Also, the frequency of ocular adverse events was low and compared favorably to the vehicle used in clinical trials. Is ELESTAT® contraindicated for any patients? ELESTAT® ophthalmic solution is contraindicated in those patients who have shown hypersensitivity to epinastine or any of the other ingredients. The preservative in ELESTAT®, benzalkonium chloride (BAK), may be absorbed by soft contact lenses. Contact lenses should be removed prior to instillation of ELESTAT® ophthalmic solution and may be reinserted 10 minutes following its administration. Can I prescribe ELESTAT® for my pediatric patients? ELESTAT® ophthalmic solution is appropriate for use by adults and children 3 years of age and older suffering from ocular itching due to allergic conjunctivitis. The safety and efficacy of ELESTAT® in pediatric patients below the age of 3 years have not been established. Who is the ideal patient for ELESTAT®? Anyone suffering from ocular itching associated with allergic conjunctivitis is an ideal candidate for ELESTAT® ophthalmic solution. Because ELESTAT® is effective at reducing the severity of ocular itching due to allergic conjunctivitis, it is an excellent choice for any patient who suffers from this common symptom. In a survey of 473 patients, research shows that 88% of patients who are prone to allergic conjunctivitis experience ocular itching and 67% are extremely bothered by this symptom. Seventy-nine percent also said it was extremely important to alleviate this symptom. Moreover, approximately one third of those surveyed were dissatisfied with their current ocular itching treatment. PHARMACOLOGY What is the mechanism of action for ELESTAT® ophthalmic solution? ELESTAT® has a multi-action effect that inhibits the allergic response 3 ways: Action 1 stabilizes mast cells by preventing mast cell degranulation to control the allergic response. Action 2 prevents histamine binding to both the H1- and H2-receptors to stop itching and provide lasting protection. Action 3 prevents the release of proinflammatory chemical mediators from the blood vessel to halt progression of the allergic response. The multi-action efficacy of ELESTAT® ophthalmic solution provides the fast-acting, long-lasting ocular itching relief your patients are looking for. How does ELESTAT® differ from other anti-allergy eye drops? ELESTAT® is an ophthalmic medication indicated for the prevention of itching associated with allergic conjunctivitis. Its multi-action antihistamine and mast cell-stabilizing activity significantly reduces ocular itching — the primary complaint of allergic conjunctivitis sufferers. Only ELESTAT® ophthalmic solution labeling cites the prevention of histamine binding to both the H1- and H2-receptors. See the Mode of Action in action. Click here. How is ELESTAT® preserved? ELESTAT® ophthalmic solution contains 0.01% benzalkonium chloride (BAK), a very low concentration of the preservative most commonly used in ophthalmic solutions. What is the dosing regimen for ELESTAT® ophthalmic solution? The recommended dosage of ELESTAT® is 1 drop in each eye twice a day (BID). Treatment should be continued throughout the period of exposure (ie, until the pollen season is over or until exposure to the offending allergen is terminated), even when symptoms are not present. Can ELESTAT® be used with other ophthalmic medications? Yes. ELESTAT® ophthalmic solution can be safely administered along with other ophthalmic medications. If more than one topical ophthalmic product is being used, the products should be administered at least 5 minutes apart. CLINICAL TRIALS What were the results of the ELESTAT® clinical trial? In the Phase III clinical study conducted by Abelson et al, ELESTAT® ophthalmic solution was shown to be an effective treatment for patients suffering from ocular itching due to allergic conjunctivitis. In this single-center, double-masked, randomized, vehicle-controlled, conjunctival antigen challenge study, two initial antigen challenges were administered to determine the level of symptoms that could be provoked in the absence of any treatment. This was followed by a further challenge 2 weeks later, when ELESTAT® ophthalmic solution was compared to vehicle in paired eyes; in order to evaluate the onset of action (ocular itch reduction), prior to the antigen challenge, patients received 1 drop of vehicle in one eye and 1 drop of ELESTAT® in the other eye (day 21). Ocular itching was graded on a 0 to 4 scale (0 = none, 1 = intermittent tickle, 2 = mild continuous, 3 = severe, 4 = incapacitating). ELESTAT® ophthalmic solution was significantly better than vehicle at reducing the severity of ocular itching — ELESTAT® achieved up to an 81% reduction compared to 18% with vehicle. The effect of ELESTAT® ophthalmic solution was fast, with relief of ocular itching within 3 minutes. ELESTAT® was very well tolerated by patients. The frequency of ocular adverse events was low and compared favorably to vehicle. ELESTAT® delivers fast relief from ocular itching, but does it last? Yes. ELESTAT® ophthalmic solution provides significant, sustained ocular itch control for up to 12 hours. In fact, at the 12-hour time end point, study patients sustained a 62% improvement in ocular itching compared to a 23% improvement with vehicle. SAFETY/COMFORT What are the side effects of ELESTAT® ophthalmic solution? ELESTAT® is very well-tolerated. The frequencies of ocular adverse events were low and compared favorably to vehicle. The most frequently reported adverse events were burning sensation in the eye (8%), folliculosis (3%), hyperemia (1%), and pruritus (1%). The most frequently reported nonocular adverse events were infection (cold symptoms and upper respiratory infections) seen in approximately 10% of patients, and headache, rhinitis, sinusitis, increased cough, and pharyngitis seen in approximately 1% to 3% of patients. Some of these events were similar to the underlying disease being studied. What is the pharmacological basis for the safety of ELESTAT® ophthalmic solution? The safety of ELESTAT® in allergic conjunctivitis is largely a factor of its pharmacokinetics. Very little of the active ingredient, epinastine, penetrates the eye; there is low systemic absorption; its pharmacokinetics are linear; less than 10% is metabolized; and its clearance is rapid. Epinastine does not penetrate the blood/brain barrier and, therefore, is not expected to induce side effects of the central nervous system. Is ELESTAT® comfortable to use? ELESTAT® ophthalmic solution has a pH range of 7 — similar to natural   tears — so your patients will find it soothing to the eye upon instillation. Are there any precautions about prescribing ELESTAT® for pregnant women? There have been no adequate and well-controlled studies in pregnant women. In an embryofetal developmental study in pregnant rats, maternal toxicity with no embryofetal effects was observed at an oral dose that was approximately 150,000 times the maximum recommended ocular human dose (MROHD). Because animal reproduction studies are not always predictive of human response, ELESTAT® ophthalmic solution should be used during pregnancy only if the potential benefit justifies the possible risk to the fetus. FREQUENTLY ASKED QUESTIONS BIBLIOGRAPHY Abelson MB, Gomes P, Crampton HJ, Schiffman RM, Bradford RR, Whitcup, SM. Efficacy and tolerability of ophthalmic epinastine assessed using the conjunctival antigen challenge model in patients with a history of allergic conjunctivitis. Clin Ther. 2004:26(1):35-47. Bielory L. Ocular allergy treatments. Clin Rev Allergy Immunol. 2001;20(2):201-213. Data on file, Allergan, Inc.; Adult Ocular Allergy Attitudes Evaluation, December 2003. Data on file, Inspire Pharmaceuticals, Inc. Friedlaender M, Scharf L, Brashears D. Control of ocular allergy symptoms by epinastine HCl 0.05% in a conjunctival antigen challenge evaluation. Poster presented at: 8th Winter Refractive Surgery Meeting of the European Society of Cataract and Refractive Surgeons; January 23-25, 2004; Barcelona, Spain. Kamei C, Akagi M, Mio M, et al. Antiallergic effect of epinastine (WAL 801 CL) on immediate hypersensitivity reactions: (I). Elucidation of the mechanism for histamine release inhibition. Immunopharmacol Immunotoxicol. 1992;14(1-2):191-205. Kohyama T, Takizawa H, Akiyama N, Sato M, Kawasaki S, Ito K. A novel antiallergic drug epinastine inhibits IL-8 release from human eosinophils. Biochem Biophys Res Commun. 1997;230(1):125-128. Matsushita N, Aritake K, Takada A, et al. Pharmacological studies on the novel antiallergic drug HQL-79: II. Elucidation of mechanisms for antiallergic and antiasthmatic effects. Jpn J Pharmacol. 1998;78(1):11-22.

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