Help patients avoid adverse effects of both OTC, prescription anti-allergy agents

Issue: April 1998

With an increasing number of antihistamines available, it seems there is no allergy your patients cannot conquer once you have made the proper diagnosis. Many of the newer, second-generation antihistamines offer patients the benefits of allergy relief without the side effects of their first-generation predecessors, namely, drowsiness and dry mouth.

But when considering which new anti-allergy medicine is right for your patient, you may also want to quiz patients on which over-the-counter ophthalmic decongestants or decongestant/antihistamine they might be using. Inexpensive and accessible, patients often misuse and overuse these products because they do not consider them medication. And in some cases, patients can actually cause chronic conjunctivitis before you see them in the office.

Don't forget dry eye

Another caveat with allergy treatment is that many patients who suffer from ocular allergies also have dry eyes; therefore, treating the dry eye component should be part of any therapy, said Randall Thomas, OD, FAAO, who is in practice in Concord, N.C.

"In many patients, if you treat the dry eye problem, the secondary opportunistic allergy expression just goes away because, in fact, they're dry," he said. "Artificial tears, which are 100% safe, can cure a whole bunch of pseudo or secondary allergy problems."

Dr. Thomas agreed there is a wide choice of allergy medicines today and that, in his practice, Livostin (levocabastine HCl, Ciba Vision) is the drop prescribed most often. "Livostin is the one we're most comfortable with," he said, "and after that it's a toss-up between Patanol (olopatadine, Alcon) and Acular (ketorolac tromethamine, Allergan), which are two fine additional eye drops."

Dr. Thomas said none of his patients has experienced any adverse effects with these prescription-only anti-allergy medicines. "They are all so safe," he said. "However, the exception to this can be found in those former prescription drugs that are now over-the-counter."

Beware of OTC agents

These combination ophthalmic decongestants contain one of the following vasoconstrictors - naphazoline, tetrahydrozoline or phenylephrine - and can be misused by patients, Dr. Thomas said, which in turn can lead to chronic conjunctivitis. He noted a study published last year in Archives of Ophthalmology to underscore this point.

"That study documented cases of chronic conjunctivitis because of patient chronic use and abuse of these readily available, over-the-counter medicines," Dr. Thomas said. "The vasoconstrictive effects of those medicines, when used over and over, can cause a chronic inflammation or dilation of the conjunctival blood vessels."

This effect has not gone unnoticed by the Food and Drug Administration, which has received more than 400 adverse drug experience reports of pupil dilation since approving the over-the-counter use of three topical antihistamine-vasoconstrictor products in the past 3 years. A proposed rule published in the Feb. 23 Federal Register seeks to include a new warning statement for over-the-counter ophthalmic drug products containing ephedrine, naphazoline, phenylephrine and tetrahydrozaline. The proposed new warning label language would include the phrase, "Pupils may become dilated."

The warning could also include a statement to the effect that the dilation is temporary and not harmful. The proposed warning would also specify that patients with narrow angle glaucoma should not take the product except under the supervision of a physician. The previous warning label did not specify narrow angle glaucoma.

Patterns of conjunctivitis

In the study published in Archives of Ophthalmology in January 1997, Soparkar and colleagues set out to describe patterns of conjunctivitis caused by over-the-counter ophthalmic decongestants.

Using medical records from patients examined during the past 12 years by two external disease specialists and from patients examined during the past 4 and 6 months at two general ophthalmology clinics, researchers were interested only in patients with a primary diagnosis of conjunctivitis.

Cases were excluded if other ocular surface disease was present, if nondecongestant eye drop use occurred within 2 weeks of presentation or if follow-up failed to note a reduction in conjunctival inflammation once the drops were discontinued. Based on these criteria, researchers identified 70 patients (137 eyes) with ophthalmic decongestant-related conjunctivitis. Patients ranged in age from 18 to 82 years. Forty-three patients were women; 27 were men.

The frequency of daily eye drop application in these patients ranged from one to 12 times, and ocular symptoms on presentation included eyelid swelling, epiphora, irritation, itching, burning, pain, foreign-body sensation or redness.

Twelve ophthalmic decongestants were implicated. All are available over-the-counter and contain one of the following adrenergic agonist agents - naphazoline (found in seven drops), tetrahydrozoline (found in four drops) or phenylephrine (found in one drop).

Three patterns identified

Researchers identified three clinical patterns of conjunctivitis: conjunctival hyperemia in 50 cases (71%); follicular conjunctivitis in 17 cases (24%); and blepharoconjunctivitis in three cases (4%).

Patients were first treated by discontinuing the topical medication. Only 24 patients were then prescribed a corticosteroid drop. The time to resolution of signs and symptoms for all cases of conjunctivitis ranged from 1 to 24 weeks. Three patients who were rechallenged with new preparations of their vasoconstrictors had a relapse of their signs and symptoms.

In their discussion, researchers noted, "The incidence of adverse reactions to ophthalmic decongestants is unknown. Even if the incidence is low, the number of patients suffering reactions may be substantial because more than 15 million bottles of these eye drops are sold each year in the United States."

This diagnosis, they noted, relies on excluding other ocular surface conditions and by asking patients specifically about their use of over-the-counter products they do not consider to be medications. And, "the longer the duration of eye drop use prior to presentation, the longer the time to recovery," the researchers said.

This study was supported in part by a grant from the Heed Ophthalmic Foundation (Cleveland), an unrestricted grant from Research to Prevent Blindness Inc. (New York) and a grant from the National Eye Institute.

Educate patients about OTC

Dr. Thomas said he now tries agents to steer patients away from these over-the-counter antihistamines and to explain their potential role in perpetuating chronic conjunctivitis.

"It takes months for this condition to completely resolve by stopping those vasoconstrictors once you figure out the problem," he said. "It's not a quick fix by any means."

Dr. Thomas, who lectures with Ron Melton, OD, on the use of ophthalmic medications, said they now encourage their audiences to caution patients against using over-the-counter ophthalmic decongestants to treat itching, burning, red eyes.

Siret D. Jaanus, PhD, echoed the same clinical concerns. "Patients can get into trouble if they use over-the-counter oral antihistamines or antihistamine-decongestant combinations," she said, "because they may not realize their ability to drive or work is impaired, or they can mask symptoms that should be looked at by their doctor."

In addition, a patient may develop tolerance to an over-the-counter product. "Make patients aware of this possible effect," said Dr. Jaanus, "and encourage them to try the noncombination drugs first, either the antihistamine or the decongestant, to solve their problem."

First-generation side effects

Dr. Jaanus is chair of biological science at the State University of New York College of Optometry. While she feels the first-generation oral allergy medications - also called sedating antihistamines - do have a place in therapy, it is a smaller role than many patients realize.

"The problem with the first-generation drugs is that patients can get central nervous system side effects," Dr. Jaanus said. These include drowsiness, dizziness, incoordination and blurred vision. The degree to which a patient notices these effects depends on which medication they take, but patients can also heighten these effects in two ways, she said, by drinking alcohol or by taking another central nervous system medication.

The first-generation antihistamine Dr. Jaanus feels most comfortable recommending is chlorpheniramine (Chlor-Trimeton, Schering). "This seems to be the least sedating and has been around a long time," she said.

Patients might also be advised to avoid possible side effects by taking an over-the-counter medication at night, she said, but also noted that some patients could wake up with a "drug hangover" and still feel drowsy.

Clinicians should be aware of the appropriate doses of first-generation antihistamines and for all medications in general, especially for children and the elderly. "In both populations, a lower dose may be appropriate to avoid side effects," Dr. Jaanus said.

Nonsedating options

Patients who need a nonsedating antihistamine can turn to second-generation medications. "These drugs are slightly more expensive and available by prescription only, but are helpful in that they are nonsedating and have very few side effects," Dr. Jaanus said.

There are currently four antihistamines available in this second-generation category - Allegra (fexofenadine, Hoechst Marion Roussel), Claritin (loratadine, Schering), Hismanal (astemizole, Janssen) and Zyrtec (cetirizine, Pfizer).

A fifth drug, Seldane (terfenadine, Marion Merrell Dow), was pulled from the market because of its potential drug-drug interaction and effect on cardiac function, Dr. Jaanus said. "With Seldane, drug levels were hard to control, and, at higher blood drug levels or if the patient took certain drugs concurrently, cardiac abnormalities were observed," she said.

With fexofenadine, Dr. Jaanus said, patients can generally receive the same benefits as terfenadine but not encounter the same risks. "Allegra is the first metabolite of Seldane, and it does not have to pass through the liver," she said.

Astemizole is less frequently prescribed, she said, because it has a long half-life, is eliminated slowly from the body and, patients run the risk of overdosing because its onset of action is delayed. Astemizole also carries the same warning regarding potential cardiac adverse effects as did terfenadine. "Patients who do not feel the benefit of the drug within a few hours may take more, which could lead to side effects," she said.

Fewer side effects

The second-generation antihistamine that seems to exhibit fewest side effects, according to Dr. Jaanus, is loratadine. "I feel comfortable with Claritin," she said. "The onset is about the same as Allegra - less than 4 hours for the patient to get the effect - and it is taken once a day with no risk of cardiac problems."

The newest drug in this category to become available, cetirizine, also offers patients a relatively fast onset of action, Dr. Jaanus said, with once-daily dosing. "It can also be administered twice daily, although it is recommend to start out once a day," she said. "Cetirizine and Claritin have been tested at higher doses and blood levels of the drug were checked. It was found that even at higher levels, they do not seem to affect the heart."

The one drawback to cetirizine, she noted, is that it can cause some sedation in patients, usually in adults more than children. "If you exceed the recommended dose of 10 mg per day, between 6% and 10% of test subjects said they experienced some drowsiness," Dr. Jaanus said.

For Your Information:

Randall Thomas, OD, FAAO, may be contacted at 6017 Havencrest Drive, Concord, NC 28027. Dr. Thomas has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any company mentioned. Siret D. Jaanus, PhD, may be contacted at 100 East 24th St., New York, NY 10010; (212) 780-4900; fax: (212) 780-5174; e-mail: sjaanus@SUNYopt.edu. Dr. Jaanus has no direct financial interest in any of the products mentioned in this article, nor is she a paid consultant for any company mentioned.

Additional Reading

Soparkar CNS, Wilhelmus KR, Koch DD, Wallace GW, Jones DB. Acute and chronic conjunctivitis due to over-the-counter ophthalmic decongestants. Arch Ophthalmol. 1997;115:34-38.