Special Section Sponsored By Ista Pharmaceuticals

When Treating Ocular Itch Associated With Allergic Conjunctivitis, Be Selective

The mechanism of action of BEPREVE selectively targets the key mediator of ocular itch, interrupting the allergic cascade and bringing fast, effective relief.

By John R. Favetta, MD, PharmD
North Arlington, NJ

If I had to use just one word to describe allergy season in the northeastern United States, that word would be “intense,” especially this year. A snowy winter combined with record rainfall over the summer means that lush greenery and the associated pollen abound. In my comprehensive ophthalmology practice, we have what I suspect is the usual mix of patients with allergic conjunctivitis: those who know they are allergic and come in to the office as soon as they sense their symptoms flaring and those who tend to wait until their symptoms are severe before seeking help. My first-line therapy for ocular itching associated with allergic conjunctivitis in both these groups is BEPREVE® (bepotastine besilate ophthalmic solution) 1.5% (ISTA Pharmaceuticals, Inc.).

Mechanism of action

BEPREVE is a highly selective histamine H1 receptor antagonist.¹ Its selectivity for H1, the primary mediator of ocular itching associated with allergic conjunctivitis, contributes to its efficacy, durability and safety. In clinical trials, BEPREVE rapidly controlled the symptoms of ocular itching.² At onset of action (3, 5 and 7 minutes), 95% of eyes dosed with BEPREVE in clinical trials experienced a statistically and clinically significant improvement in ocular itching, compared to 47% dosed with placebo. Eight hours after this single dose, 90% of eyes retained this level of improvement. For patients with severe itching, the effect of BEPREVE was even more impressive. Fully 68% of eyes with severe itching experienced complete relief at 3 minutes following a single drop, compared to 3% of those who received a placebo drop.³

BEPREVE also has very low binding affinity for muscarinic, H3, alpha-adrenergic and beta-adrenergic receptor sites, all of which have been associated with side effects, such as sedation and dryness.¹ BEPREVE's very low binding affinity for off-target receptors is reflected in its safety profile. In a large safety study, slightly fewer patients dosed with BEPREVE reported dry eye than those given placebo drops (BEPREVE: 1.0% and placebo: 1.7%), and neither drowsiness nor dry mouth was reported.⁴ In addition, BEPREVE was as comfortable as the placebo drop on instillation and 5 minutes later.⁵ The most common reported adverse reaction occurring in approximately 25% of subjects was a mild taste following instillation. Other adverse reactions occurring in 2% to 5% of subjects were eye irritation, headache and nasopharyngitis.

BEPREVE is also a potent mast cell stabilizer, which is an important mechanism in the early phase of the allergic cascade and to prevent the late phase.⁶ When an individual becomes sensitized to an antigen, the immune system produces immunoglobulin E (IgE) antibodies. Re-exposure to the allergen causes a “lock-and-key” attachment of the antigen to the surface of the mast cell that has been sensitized, inducing mast cell degranulation which releases histamine and other secondary mediators. BEPREVE stabilizes the mast cell, preventing it from breaking down and releasing inflammatory mediators.

Cornerstone treatment

BEPREVE has favorable pharmacokinetic and pharmacodynamic properties and an excellent safety profile. It offers fast, long-lasting relief, which makes it the cornerstone of my approach to treating itching associated with allergic conjunctivitis.

Bepotastine is Highly Selective For H1 And Has Very low Binding Affinity For Receptors That Cause Side Effects ¹

References

1. Kato M, Nishida A, Aga Y, et al. Pharmacokinetic and pharmacodynamic evaluation of central effect of the novel antiallergic agent bepotastine besilate. Arzneimittelforschung. 1997;47:1116-1124.
2. Williams JI, Schooley GL, Gow JA, McNamara TR. BEPREVE™ 1.5% provides clinically meaningful reduction in allergen-induced ocular itching for subjects in an analysis of two phase 3 conjunctival allergen challenge (CAC) clinical trials. J Allergy Clin Immunol. 2010;125(suppl. 1):AB38.
3. Clark JC, Williams JI, Gow JA, Abelson MB, McNamara TR; Bepotastine Besilate Ophthalmic Solutions Clinical Study Group. Bepotastine besilate ophthalmic solution 1.5% rapidly eliminates ocular itching in more severely allergic subjects in the conjunctival allergen challenge model of allergic conjunctivitis. Poster presented at: Eastern Allergy Conference; May 6-9, 2010; Palm Beach, FL.
4. Data on file. ISTA Pharmaceuticals®, Inc.
5. Williams JI, Ackerman SL, Dao JT, Reddy TA, McNamara TR, Gow JA. The ocular comfort of bepotastine besilate ophthalmic solution 1.5% in a safety clinical trial. Poster presented at: 88th Annual Meeting of the American Society of Optometry; November 17-20, 2010; San Francisco, CA.
6. Yato N, Murata T, Saito N, Sakai A, Kikuchi M, Tsuzurahara K, et al. Anti-allergic activity of bepotastine besilate (TAU-284), a new anti-allergic drug. Folia Pharmacol Jpn. 1997;110:19-29.