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Since the 2009 approval of bepotastine besilate ophthalmic solution 1.5% for ophthalmic use in the United States, further analysis of clinical trial data and new information from additional studies have revealed more about the drug's clinical utility.
New evidence is emerging on duration of action, ocular comfort, and efficacy against ocular itching and redness, said Richard L. Lindstrom, MD, Minnesota Eye Consultants, Bloomington, MN. Dr. Lindstrom was the author of a paper on the expanded results reported from various studies of bepotastine, published in U.S. Ophthalmic Review (2011;4:101-103).
"The primary symptom of allergic conjunctivitis is bad itching, so you want a drug that has a rapid onset of action and is effective at reducing itch," Dr. Lindstrom said.
Following that initial improvement, patients also want long-lasting relief from their symptoms. New data from a single-site trial used to support FDA approval shows that bepotastine not only achieved statistically and clinically significant reductions in subject-assessed ocular itching at 3, 5, and 7 minutes after a single dose, but also at 16 hours, he said.
Compared with placebo, a significantly higher number of patients in both the bepotastine per-protocol population (p < 0.001) and the baseline severe itching subpopulation (p = 0.005) achieved complete or near-complete elimination of itch at 16 hours.
Those findings are also relevant to another important characteristic of an anti-allergy medication-the dosing schedule, Dr. Lindstrom said.
Bepotastine is indicated for twice-daily dosing in the treatment of itching associated with allergic conjunctivitis, whereas other antihis-tamine-mast cell stabilizers, such as olopata-dine hydrochloride ophthalmic solution 0.2% (Pataday, Alcon Laboratories) and alcaftadine ophthalmic solution 0.25% (Lastacaft, Aller-gan) are indicated for once-daily dosing.
Nevertheless, since bepotastine appears to have good efficacy to at least 16 hours, it could be used once a day in maintenance and prophylactic situations, Dr. Lindstrom said. In a subset of patients, a single daily dose may provide satisfactory symptomatic relief during an acute allergic reaction.
An environmental exposure study, the results of which were first reported in early 2011, also supports prior data showing that bepotastine is superior to placebo in reducing ocular itching and conjunctival redness. The randomized, double-masked, placebo-controlled, parallel-group, natural exposure clinical trial, conducted at 12 sites, included 123 patients who were randomly assigned to receive bepotastine and 122 to placebo. Patients were treated for 14 days and asked to record signs and symptoms, including instantaneous grades for itching and redness just before each dose.
At the end of the treatment period, the patients who received bepotastine showed statistically significant improvement in the reduction from baseline in mean instantaneous grades of both ocular itching (p = 0.007) and conjunctival redness (p = 0.001) That type of environmental exposure study supplements findings from the CAC studies conducted during the approval process, Dr. Lindstrom said. In that instance, the patients suffered active rhinoconjunctivitis and used the study medication for 2 weeks, which provided information about bepotastine from a more natural setting. Researchers also were able to evaluate the drug's efficacy against a wide range of signs and symptoms.
The additional data that are accumulating support those conclusions that bepotastine is a very effective drug, Dr Lindstrom noted.
Side effects and comfort are also important considerations when prescribing medication for ocular allergies, particularly since those factors can affect patient compliance to therapy, Dr. Lindstrom said. One of the most common complaints is exacerbation of dry eye. A significant number of patients with seasonal or allergic conjunctivitis also have either aqueous-deficient or evaporative dry eye with associated meibomian gland dysfunction.
"Some forms of systemic or topical anti-histamines will make the dry eye worse, but bepotastine in particular does not seem to do this," Dr. Lindstrom said. "In addition, the bepotastine seems to have some benefit in reducing the symptoms of the associated rhinitis as it passes through the lacrimal system into the nose."
Some topical or oral antihistamines also can induce drowsiness in highly sensitive patients, which could be a concern when they are driving, at work, or in other situations where they need to stay alert. In the studies that were the basis for approval of bepotastine, patients in the active treatment groups did not report any drowsiness, dry eye, or dry mouth.
Since the drug's approval, additional smaller comparative studies in the clinical setting have begun. The first to be reported showed that bepotastine and olopatadine were significantly more comfortable than either of two over-the-counter ketotifen fumarate ophthalmic solution 0.025% antihistamine eye drops, (Zaditor, No-vartis/Alcon; Alaway, Bausch + Lomb). The 36 patients in the study were asked to rate the four drugs and compare them with a preservative-free artificial tear.
Richard L. Lindstrom, MD
Dr. Lindstrom is a consultant for Alcon Laboratories, Bausch + Lomb, and ISTA Pharmaceuticals.