Proposed Ruling Affects OTC Ophthalmic Drug Manufacturers

Complaints prompt FDA to consider requiring new warnings on product labeling.


Pupil dilation when using over-the-counter (OTC) eye drops to relieve itching and redness is not usually considered a harmful side effect. Yet some consumers discontinue use of the products as a result. Because of that, as well as the number of complaints received about the effect, FDA may amend the final monograph on the labels for OTC ophthalmic drug products.

The proposed rule appeared in the February 23, 1998, edition of the Federal Register (63FR: 8888—8890).

The current monograph, covering the ophthalmic vasoconstrictor active ingredients ephedrine hydrochloride, naphazoline hydrochloride, phenyl-ephrine hydrochloride, and tetrahy-drozoline hydrochloride, requires the warning, "If you have glaucoma, do not use this product except under the advice and supervision of a doctor."

However, in the past three years, FDA has approved three new ophthalmic drug products. These are not covered under the monograph because one of their active ingredients, phenir-amine maleate, is not covered.

FDA has received over 400 adverse drug experience (ADE) reports complaining about dilated pupils after use of those three new products. Dilation is a known side effect of vasoconstrictors—even in the low concentrations used in OTC products—especially for people who wear contact lenses, have an abraded cornea, or have lightly colored irises. But in 1980, the Advisory Review Panel on OTC Ophthalmic Drug Products did not recommend a labeling warning because pupil enlargement is not clinically significant and does not affect pupil reactivity.

FDA now proposes to change its position because of the complaints. It hopes the number of ADE reports will be reduced and that consumers will not stop using the products because of unexpected dilation.

So the agency proposes to add the following wording to OTC vasoconstrictor drugs: "Pupils may become dilated (enlarged)." It is seeking comment on whether to further add a phrase such as "This is temporary and not serious," and whether it should be required or optional.

The current glaucoma warning exists because pupil dilation caused by an ophthalmic vasoconstrictor drug can trigger an attack of narrow-angle glaucoma in a susceptible patient. In the three newest products, the warning has been phrased as "Do not use this product if you have narrow-angle glaucoma unless directed by a physician." Because that is the only type of glaucoma applicable and many patients are told by their doctor what kind of glaucoma they have, the agency proposes to amend the original monograph warning to "If you have narrow-angle glaucoma, do not use this product except under the advice and supervision of a doctor."

FDA says it recognizes that space on OTC ophthalmic drug product labels is limited, but considers the new words necessary because of the number of complaints. It proposes that the new rule become effective 12 months after publication of the final rule, but is seeking comment on whether to extend that to 18 months. Existing products have been labeled under the current monograph for nine years, and a longer effective date should enable manufacturers to exhaust existing labels and implement the new labels in the normal course of reordering labeling. Also, an extended date might allow for the new rule to be implemented at the same time as a new OTC drug labeling format under consideration.

The agency estimates that relabeling costs will average $2000 to $3000 per stock-keeping unit, for a nationwide total of $200,000 to $300,000, and says that amount may even be lower because most of the modifications will be made by private label manufacturers who tend to use simpler and less-expensive labeling.

The comment period was scheduled to end May 26. For more information, contact FDA's Center for Drug Evaluation and Research at 301/827-2307.

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