Allergy treatment: remember the standbys, consider the newer agents

With nearly 20 prescription therapies for ocular allergy approved by the Food and Drug Administration (FDA), it is becoming more and more challenging for practitioners to choose appropriate medications for their patients. In the United States, approximately 20% of the population suffers from allergies, and about 50% of these patients will need treatment.

Practitioners can choose from mast-cell inhibitors that block allergic reactions or antihistamines, which work well in patients with more severe allergies. Combination drops are newly available, as are more traditional treatments for severe cases, such as steroids and immunosuppressants.

Alamast

Santen Inc., in Napa, Calif., manufacturers Alamast (pemirolast potassium ophthalmic solution 0.1%), an FDA-approved mast-cell stabilizer for the temporary prevention of itching due to allergic conjunctivitis.

Mast-cell stabilizers work by blocking allergic reactions. Studies both in vivo and in vitro have confirmed that Alamast stops the release of inflammatory mediators in response to antigens. Researchers said that the drug may also inhibit chemotaxis of eosinophils into ocular tissues and also block the release of the mediators from eosinophils.

“Mast-cell stabilizers work very well. When these drugs work to stabilize the mast cell, there is no degranulation of the mast cell, and, therefore, the allergic cascade of mediators is eliminated,” Gregg J. Berdy, MD, a cornea/external disease specialist, told Ocular Surgery News in a special report on ocular allergy.

He added that while the solution is indicated for one to two drops in each eye four times daily, its potential for twice-daily dosing may improve compliance. Dr. Berdy said that he has found the drop to be comfortable.

Data presented at the 12^th Congress of the European Society of Ophthalmology showed that patients treated with Alamast experienced significantly less ocular itching than placebo-treated patients. Patients in this study were treated during ragweed allergy season; they began taking the solution prophylactically, four times daily, for 1 to 2 weeks prior to the usual onset of the ragweed allergy season.

Researchers found that statistically significant differences in allergy symptoms were seen as early as the first week of allergy season. Using a post-season conjunctival allergen challenge model, researchers confirmed that mean itching at 3 minutes and worst itching during the first 10 minutes after the challenge were both lower in Alamast patients vs. placebo patients. This difference was statistically significant.

Alamast’s prescribing information notes that while decreased itching may be obvious within a few days following treatment, some patients may need treatment for up to 4 weeks. Adverse events in clinical trials were generally mild and similar to those found in placebo patients.

Alrex

Alrex (lodeprednol etabonate ophthalmic suspension 0.2%, Bausch & Lomb) is indicated for the temporary relief of signs and symptoms of seasonal allergic conjunctivitis. It falls under the steroidal anti-inflammatory category.

Bruce E. Onofrey, OD, RPh, who is responsible for primary eye care services at Lovelace Medical Center in Albuquerque, uses Alrex as a second-line treatment for patients who are not responding to other medications. “Some patients with allergic conjunctivitis have some degree of inflammation and resistance to ‘front-line’ medications. I’ll reserve Alrex for those people who are resistant to treatment with drugs such as Patanol (olopatadine HCl 0.1% ophthalmic solution, Alcon), Alocril (nedocromil sodium ophthalmic solution 2%, Allergan) and Optivar (azelastine HCl ophthalmic solution, 0.05%, Bausch & Lomb). It has an excellent anti-inflammatory effect. Once we control it with Alrex, I’ll step down to another drug for long-term use,” Dr. Onofrey told Primary Care Optometry News.

In addition to its current indication for allergic eye disease, Alrex has applications for various superficial ocular inflammatory diseases, added Dr. Onofrey.

Alocril

Alocril is also approved as a topical treatment for itch associated with allergic conjunctivitis. Cornea/external disease specialist Stefan D. Trocme, MD, told Primary Care Optometry News that the trend for allergy treatment is using drugs with dual or multiple action.

“Alocril stabilizes and prevents actions from eosinophils and neutrophils, and it prevents neuronal actions,” Dr. Trocme said. It also prevents other surface cells from secreting inflammatory mediators and decreases chemotaxis. He added that it is the first ocular allergy drug to have more than three actions.

Unlike traditional mast-cell stabilizers, Alocril acts quickly. It should be used twice daily, and no stinging is associated with it. The recommended dosage is one or two drops in each eye during pollen season or until exposure to the offending allergen stops. The most common adverse event associated with the drop is headache, occurring about as often in both treatment and placebo patients.

A study comparing nedocromil drops to oral terfenadine and placebo found that nedocromil was most useful in treating seasonal allergic conjunctivitis. The report, in Clinical Therapeutics, found that 36.7% of nedocromil-treated patients experienced symptom relief in 2 minutes or less vs. 24.7% of terfenadine-treated patients and 29.1% of placebo patients.

The study found that 77.2% of the nedocromil patients reported symptom relief in 15 minutes or less vs. 58.8% of the terfenadine group and 55.8% of the placebo patients. The difference for nedocromil was statistically significant.

Zaditor

“Zaditor is unique because of its mechanism of action,” Michael Raizman, MD, cornea/external disease specialist from New England Eye Center and Ophthalmic Consultants of Boston told Ocular Surgery News. “It is a powerful antihistamine and also stabilizes mast cells and inhibits eosinophils.”

Zaditor (ketotifen fumarate ophthalmic solution, 0.025%, Novartis Ophthalmics) is approved for seasonal and nonseasonal allergic conjunctivitis, along with other classic allergy symptoms. According to Novartis, the drops work quickly and provide relief from symptoms for up to 12 hours.

“It doesn’t work for every patient, but it’s by far the best allergy drug that we’ve seen come along in this category,” Walter S. Ramsey, OD, FAAO, told Primary Care Optometry News. Dr. Ramsey is in private practice in Charleston, W.Va. He said he uses it mainly as first-line treatment for inflammation caused by allergy.

In clinical trials of Zaditor, it was shown to inhibit the release of chemical mediators such as histamine and leukotrienes from sensitized mast cells and to inhibit the binding of histamine to the H₁ receptor. This drug also decreases eosinophil chemotaxis and activation.

Dr. Raizman explained that Zaditor is a selective, noncompetitive histamine receptor antagonist, so it inhibits the activity of a major chemical mediator involved in type 1 hypersensitivity reactions. As a mast-cell stabilizer, the drug calms the major cellular component of the allergic cascade, thus preventing the mast cell from releasing mediators that cause allergic reactions. Trials of Zaditor showed that it was effective in preventing itching, ranging from 15 minutes after dosing to 12 hours.

Patanol

Patanol, one of the most widely prescribed ocular allergy medications, is often regarded as the “gold standard” in ocular allergy medication. It recently received an expanded indication approval from the FDA.

Clinical trials conducted by Mark B. Abelson, MD, of the Schepens Eye Research Institute in Boston, demonstrated that olopatadine, in addition to reducing itching associated with allergic conjunctivitis, also reduces redness associated with allergic conjunctivitis. Olopatadine combines mast-cell stabilization with antihistaminic activity. Based on the results of the study, the FDA expanded the indication for olopatadine from “temporary prevention of ocular itching due to allergic conjunctivitis” to “treatment of the signs and symptoms of allergic conjunctivitis.”

Optivar

Optivar received FDA approval in May 2000. Azelastine HCl is a relatively selective histamine H₁ antagonist/mast-cell stabilizer, and it inhibits the release of histamine and other mediators from cells involved in the allergic response. Decreased chemotaxis and activation of eosinophils has also been demonstrated. According to company literature, Optivar has a rapid onset of action (within 3 minutes) and a long duration of effect (approximately 8 hours) with twice-daily dosing. Optivar has been proven to be safe in patients 3 years of age and older.

“Optivar falls into the same category of drugs as Patanol and Zaditor,” said Dr. Onofrey. “They are all antihistamine/mast-cell inhibitors. The good thing about Optivar is that it’s safe and effective, and it is approved for twice-daily dosing.”

One of the shortcomings at the moment, according to Dr. Onofrey, is that there is not enough research available yet to show its benefit over an established drug such as Patanol. Dr. Onofrey said that he will be involved in future studies that are being planned to compare the efficacy of Optivar and Patanol.

Using mast-cell stabilizers

Clinicians said that using a mast-cell stabilizer only in patients with mild to moderate symptoms should be sufficient. Joseph P. Shovlin, OD, in private practice in Scranton, Pa., told Primary Care Optometry News that the mast-cell stabilizers alone are fine when the patient’s symptoms are under control, and you can use it as maintenance or prophylactic treatment. He cited Crolom (cromolyn sodium 4%, Bausch & Lomb) and Alomide (lodoxamide tromethamine, Alcon) as good maintenance therapies for keratoconus patients to get through seasonal allergies.

Bobby Christensen, OD, FAAO, in private practice in Midwest City, Okla., suggested Alomide for long-term therapy for juvenile vernal conjunctivitis, with a secondary use for the adult form of a vernal-like condition. He added that Crolom is good for patients suffering from a low-grade giant papillary conjunctivitis from contact lenses.

Dr. Shovlin said that mast-cell stabilizers are safe and easy to use, making them a good choice for practitioners. “They all have relative spectrums of efficacy and relative safety profiles that are high, so they’re very simple and safe to use.”

Antihistamines and other therapies

Dr. Christensen prescribes an antihistamine drop alone to patients who experience moderate to severe itching but have little tarsal conjunctival matter. He added that cold compresses often help.

If the condition worsens to include redness, inflammation and matter, Dr. Shovlin said he would use a combination of a mast-cell stabilizer and an antihistamine. Dr. Christensen’s choice in this patient would be Patanol. Dr. Shovlin said he makes the jump to Patanol when the eye is more inflamed and the patient has more tarsal conjunctiva reaction.

One alternative to Patanol, however, is to use two separate drugs, Livostin (levocabastine HCl 0.05%, Novartis Ophthalmics) and Crolom. It may not be as convenient, Dr. Christensen said, but if patients are on a managed care plan that has a formulary, you can still prescribe a mast-cell stabilizer and an antihistamine.

Be cautious of steroids

Steroids may enter the picture in patients suffering from severe allergies with a lot of symptoms. Charles Slonim, MD, clinical associate professor of ophthalmology at the University of South Florida College of Medicine in Tampa, urged caution due to potential side effects. He said that clinicians should have a healthy fear of steroids, but when antihistamines, mast-cell stabilizers and the combination drugs relieve symptoms only partially, steroids will eliminate virtually all signs and symptoms of allergy.

Dr. Slonim will prescribe steroids such as Alrex and Lotemax (loteprednol 0.5%, Bausch & Lomb).

Another choice for severe allergies is cylcosporine. Dr. Raizman said he has been using a 0.05% cyclosporine drop for more than a decade in patients with severe conditions. He added that it is preferable to a steroid because it is safer long-term.

For Your Information:

• Gregg J. Berdy, MD, can be reached at 456 N. New Ballas Rd., Ste. 386, Creve Coeur, MO 63141; (314) 993-5000; fax: (314) 993-5558.
• Bruce E. Onofrey, OD, RPh, can be reached at Lovelace Medical Center, Montgomery Eye Clinic, 9101 Montgomery Blvd. NE, Albuquerque, NM 87111; (505) 275-4226; fax: (505) 275-4203. Neither Dr. Berdy nor Dr. Onofrey has a direct financial interest in the products mentioned in this article, nor is either a paid consultant for any companies mentioned.
• Stefan D. Trocme, MD, can be reached at department of ophthalmology UTMB, Clinical Sciences Building, Room 340, Galveston, TX 77550-0787; (409) 772-8104; fax: (409) 772-8106. Dr. Trocme has received research grants from Allergan.
• Michael Raizman, MD, can be reached at 750 Washington St., Boston, MA 02111; (617) 636-7625; fax: (617) 636-4866. Primary Care Optometry News could not confirm whether or not Dr. Raizman has a direct financial interest in the products mentioned in this article, or if he is a paid consultant for any companies mentioned.
• Walter S. Ramsey, OD, FAAO, can be reached at Ste. 726, Huntington Square, Charleston, WV 25301; (304) 343-3363; fax: (304) 342-3311. Dr. Ramsey has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.
• Joseph P. Shovlin, OD, can be reached at the Northeastern Eye Institute, 200 Mifflin Ave., Scranton, PA 18503; (570) 342- 3145; fax: (570) 344-1309. Dr. Shovlin has no direct financial interest in the products mentioned in this article. He is a paid consultant for Alcon.
• Bobby Christensen, OD, FAAO, can be reached at Heritage Park Vision Source, 6912 E. Reno, Ste. 101, Midwest City, OK 73110; (405) 732-2277; fax: (405) 737-4776. Dr. Christensen has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.
• Charles Slonim, MD, can be reached at 4444 East Fletcher Ave., Ste. D, Tampa, FL 33613; (813) 971-3846; fax: (813) 977-2611. Dr. Slonim has no direct financial interest in the products mentioned in this article. He is a paid consultant for Bausch & Lomb Pharmaceuticals.