Pharmacology Update

Emedastine Difumarate Ophthalmic Solution

By William T. Elliott, MD, and James Chan, PharmD, PhD

The fda has approved emedastine (emadine), Alcon Pharmaceuticals' new ophthalmic solution for allergic conjunctivitis. The drug is a potent new benzimidazole topical antihistamine that has a rapid onset of action. The drug joins this suddenly crowded market with products such as levocarbastine (Livostin), olopatadine (Patanol), and ketorolac (Acular).

Emedastine is a relatively selective histamine H1 antagonist that is reported to be 100 times more potent than levocarbastine.1-3 Emedastine inhibits histamine-induced secretions of cytokines such as interleukin 6, interleukin 8, and granulocyte macrophage colony stimulating factors from human conjunctival epithelial cell cultures in a dose-related manner4 and inhibits vascular permeability both in vitro and in vivo.1 The drug does not appear to have any effects on alpha adrenergic, dopamine, muscarinic, or serotonin receptors.1

Indication

Emedastine is indicated for the temporary relief of the signs and symptoms of allergic conjunctivitis.

Potential Advantages

In an unpublished environmental study reported by the manufacturer, physicians rated emedastine statistically better than levocarbastine (Livostin) over the course of 42 days.1 In this study, 202 patients with moderate to severe allergic conjunctivitis received ether emedastine or levocarbastine twice daily for six weeks. The study was conducted in several geographic areas with patients known to be allergic to pollen indigenous to their areas. Patients made follow-up visits on days three, seven, 14, 30, and 42 and off-therapy on day 50. Physicians assessed the patients' clinical condition using a 0-5 scale at each visit.

Emedastine, as with olopatadine, is approved by the FDA for use in patients age 3 years and older. Levocarbastine is approved for use in patients 12 years of age and older.

Potential Disadvantages

Some patients experience ocular discomfort such as burning/stinging (2.8%), pruritus (1.8%), dryness (1.3%), and blurred vision (1.0%). Dosing up to four times a day may be needed to provide adequate around-the-clock relief of symptoms.

Emedastine contains benzalkonium chloride, which may be absorbed by soft contact lenses. Patients should be instructed to wait at least 10 minutes after instilling Emedastine before inserting their contact lenses.1

Dosing Information

Emedastine is supplied as a 0.05% solution in 5-mL bottles. The recommended dose is one drop in the affected eye up to four times daily.

Comments

Allergic conjunctivitis is a type-1 hypersensitivity reaction involving IgE antibodies. Airborne allergens react with IgE immunoglobulins bound to mast cells and basal cells. This triggers the release of inflammatory mediators and the degranulation of mast cells and histamine release.5 Histamine is believed to be a principal chemical mediator of the allergic response. Emedastine is a potent histamine-1 receptor antagonist with a rapid onset of action (within minutes) and a duration of action of at least four hours.1 Clinical studies showed that it is well tolerated in terms of ocular comfort and relieves signs and symptoms of allergic conjunctivitis such as itching, redness, chemosis, and swelling. In terms of efficacy, ocular comfort, and dosing, emedastine is most similar to levocarbastine (Livostin) although an unpublished, Alcon-sponsored study suggests a statistical superiority over levocarbastine.1

Clinical Implications

Allergic conjunctivitis is a common form of ocular allergy. The estimated prevalence is about 20%. Current pharmacologic treatment includes nonsteroidal anti-inflammatory agents (ketorolac, Acular), mast cell stabilizers (cromolyn, Crolom; lodoxamide, Alomide), antihistamines (levocarbastine, Livostin), antihistamine/ decongestant combinations (i.e., naphazoline/pheniramine), and antihistamine/mast cell stabilizer (olopatadine, Patanol). NSAIDs and antihistamine-based products offer relief in the acute phase, while mast cell stabilizers are used for prophylaxis. Emedastine is most similar to levocarbastine in terms of action, efficacy, ocular comfort, and dosing. These differ from olopatadine, which is an antihistamine with mast cell stabilizing action and is dosed on a twice-daily basis.

The wholesale cost for 5 mL of emedastine is approximately $33 compared to $32 for levocarbastine and $48 for olopatadine. While the cost per bottle between emedastine and levocarbastine are the same, Alcon is claiming a price advantage due to a smaller drop size-thus a greater number of drops per bottle. If patients required more than twice daily administration with emedastine or levocarbastine, olopatadine may be less expensive, as it is dosed twice daily only.

References

    1. Emadine Product Monograph. Alcon Laboratories; 1998.

    2. Sharif NA, et al. Drug Devel Res 1994;33:448-453.

    3. Yanni JM, et al. J Ocular Pharmacol 1994;10:665-675.

    4. Weimer LK, et al. Int Arch Allergy Immunol 1998; 115:288-293.

    5. Newell FW. Ophthalmology: Principle and Concepts, 8th ed. St. Louis, MO: Mosby-Year Book; 1996:233-253.