Pharma Corner
Options for allergy patients

Mildy injected and edematous conjunctiva in a patient with allergic conjunctivitis
Source: C. Steven Foster, M.D.

Patients looking for an answer to their ocular itching in the upcoming allergy season have a new option—thoroughly vetted in Japan—that some ophthalmologists say is highly selective for certain inflammatory enzymes without causing problematic side effects.
Bepreve (bepotastine besilate ophthalmic solution 1.5%, Ista Pharmaceuticals, Irvine, Calif.) was approved by the Food and Drug Administration in September 2009 for the treatment of ocular itching associated with allergic conjunctivitis.
But bepotastine has been approved in Japan for systemic use in the treatment of allergic rhinitis since 2000. “It has a fairly longstanding history of use and a good formula for success,” said John D. Sheppard, M.D., professor of ophthalmology, microbiology, and immunology, Eastern Virginia Medical School, Norfolk, Va. “The specificity of the molecules is there and potency is improved as well.”
Francis S. Mah, M.D., co-medical director, Charles T. Campbell Ophthalmic Microbiology Laboratory, University of Pittsburgh School of Medicine, calls Bepreve a unique product that is highly selective. For example, Bepreve is highly specific to H1 receptor antagonists. It also inhibits IL-5 and LTB4, he said.
“These are other cytokines that produce the inflammatory response,” Dr. Sheppard noted. “The biochemistry of this is well documented in cellular and animal models.” Dr. Sheppard explained that although it’s difficult to link certain molecules to a human allergic symptom, IL-5 can be used as a marker of allergic disease. “So Bepreve is the medication with the best documentation for multiple mechanisms of action beyond traditional redness and itching,” Dr. Sheppard said.

Comparing drops

Dr. Mah suggested Bepreve is more selective than competitor drops such as Patanol (olopatadine hydrochloride ophthalmic solution 0.1%, Alcon, Fort Worth, Texas) and Elestat (epinastine HCl ophthalmic solution 0.05%, Allergan, Irvine, Calif.).
Although competitor drops are selective antihistimines, they do bind to and block other enzymes, he said. “Bepreve may be good in terms of not having untoward side effects,” Dr. Mah said. “But it may not do a whole lot of extra anti-inflammatory activities.”
Similar to competitor drops, Bepreve also contains mast cell stabilizing properties as well.
And although Bepreve manufacturers claim it has multiple mechanisms of action—again, related to certain cytokine inhibition and other features—Dr. Mah is waiting to observe the clinical significance. “Is that really going to impact my patients, and if so, how?” Dr. Mah wondered. “And what, if any, abilities do the conventional drops have against those [cytokines]?”
Bepreve is approved as a twice-a-day drop. Pataday (olopatadine hydrochloride ophthalmic solution 0.2%, Alcon) is only needed once-a-day.
But practically speaking, Dr. Mah said, some patients just use prescription allergy drops once-a-day, regardless of the prescribed dose. They will put a drop in during the morning, and only if symptoms persist, they will use another drop later in the day.
Interestingly, Bepreve has a “mild taste perversion” according to some research, Dr. Mah said. “It seems to be mild, not severe,” Dr. Mah said. That might affect compliance issues, but Dr. Mah doesn’t think it will. “Patients said they had a little change in taste,” he said.
For now, Dr. Mah is confident that Bepreve will be another piece of the allergy treatment puzzle to be used to help patients. “One of the unique properties of Bepreve is that it also treats non-ocular symptoms,” he said. “So one of the potential advantages is to use fewer systemic medications. You could use less nasal spray and use Bepreve to get some relief of rhinitis or systemic allergic symptoms.”
Dr. Mah also is hopeful about Bepreve simply because it’s different. Sometimes with regards to allergy medications, even though products may be treating the same class of allergy, only one will work for a certain patient. “We have excellent medications out there already, but this will enhance our ability to treat patients,” he said.

A seasonal test

As winter gives way to spring, patients will indeed be looking for something to conquer their ocular itching. Ophthalmologists said Brepreve will fall into treatment recommendations, but it is not a silver bullet.
Allergen avoidance has been preached from the mountains of ophthalmic care, and it continues to be emphasized. “If patients are familiar with their allergies—they have been to an allergist and know what triggers their reactions, like cat dander—they could avoid allergic situations,” said Stephen C. Pflugfelder, M.D., professor of ophthalmology, Baylor College of Medicine, Houston
However, if they live in an area where they know they are going to be exposed to an allergic trigger, there may be little more they can do than take allergy medication.
Hence, Dr. Pflugfelder has traditionally reached for a mast cell stabilizer and antihistamine combination for his patients. Using a medication with mast cell stabilizing properties make it more potent, and it lasts longer, he said.
There also aren’t any serious contraindications for these drugs, Dr. Pflugfelder said. There’s no toxicity. And even though such medications have not been studied in very young children, Dr. Pflugfelder said, “I would have no problems in using them in younger children.”
If the antihistamine/mast cell stabilizer combination drugs still aren’t effective in a certain patient, Dr. Pflugfelder said he would opt for a weak corticosteroid, and then finally, if that still wasn’t helping to quell symptoms, a stronger steroid—perhaps orally taken—or an immunosuppressant, such as cyclosporine. Dr. Pflugfelder was not familiar enough yet with Bepreve to comment on it.
Meanwhile, Dr. Mah said that systemic medications for allergies are improving. “In general, we’re heading toward steroid usage for allergy treatment,” he said. “But with steroids, even ‘soft steroids,’ there are potential dangers of infection, cataract, and glaucoma.”
Even with nasal medications, there are still some side effects to the eyes, Dr. Mah said. “A big worry for us is that with a systemic antihistamine, it’s going to dry the eyes out,” Dr. Mah said.
But Bepreve won’t dry eyes out, Dr. Sheppard said. “It might even be a good drop to use for concomitant ocular surface disease, like dry eye and allergy,” Dr. Sheppard said.

Editors’ note: Dr. Sheppard has financial interests with Alcon (Fort Worth, Texas) and Allergan (Irvine, Calif.). Dr. Mah has financial interests with Alcon, Allergan and Ista Pharmaceuticals (Irvine, Calif.). Dr. Pflugfelder has no financial interests related to his comments.

Contact information

Mah: 412-647-2211, mahfs@upmc.edu
Pflugfelder: 713-798-4732, stevenp@bcm.tmc.edu
Sheppard: 757-622-2203, jsheppard@vec2020.com