Manufacturers of over-the-counter non-steroidal anti-inflammatory drugs should prominently identify their products as NSAIDs on packaging, according to an FDA request.

In a supplemental labeling request letter posted June 15, the agency asks that OTCs containing ibuprofen, ketoprofen or naproxen display the word "NSAID" in parentheses following the name of the ingredient on the principal display panel.

"The word '(NSAID)' should appear highlighted in either fluorescent or color contrast or in bold type," FDA requests in the letter. "The size should be at least one-half as large as the size of the most prominent printed matter on the PDP."

Furthermore, for 12 months after introduction, the PDP should also carry the statement "See new warnings information" in contrasting type at least one-third the size of the most prominent printed matter, FDA says.

A number of requested labeling revisions are intended to provide "more specific" information about potential cardiovascular and gastrointestinal risks of OTC NSAIDs and remind consumers of the limited dose and short-term use of such products.

Separate same-day letters requesting black box warnings about CV and GI risks were sent to marketers of prescription NSAIDs, such as Pfizer's COX-2 inhibitor Celebrex (celecoxib).

The actions follow an April agency announcement and public health notice on the NSAID class, and reflect the findings of a February advisory committee meeting that pointed toward a "class effect" of increased cardiovascular risk. (¹ Also see "FDA Determines A “Class Effect” Is In Play For All NSAIDs" - Pink Sheet, 11 April, 2005., p. 3 and ² Also see "OTC NSAID Labeling Could Be In For Changes Following Advisory Panel Vote" - Pink Sheet, 28 February, 2005., p. 4).

FDA's letter to OTC firms includes a template for changes to the Drug Facts panel (see chart: " ³ FDA-Requested Adult Drug Facts Label ").

Revisions to the Drug Facts panel, along with the PDP change, suggest an attempt by the agency to raise consumer awareness of NSAIDs as a class.

The Drug Facts panel template identifies the active ingredient as an NSAID or "nonsteroidal anti-inflammatory drug" and instructs consumers: "Do not use...with any other drug containing an NSAID (prescription or nonprescription)."

The use of the term NSAID has raised an issue of potential consumer confusion for Advil marketer Wyeth (see ⁴ Also see "Wyeth Says NSAID Risk Label May Confuse Consumers" - Pink Sheet, 20 June, 2005.).

The new cardiovascular risk warning language includes a statement that use for more than 10 days or beyond the recommended dose "may increase the risk of heart attack or stroke."

Current labeling for Bayer's Aleve (naproxen sodium) simply warns consumers not to use the product for more than 10 days for pain. The ulcer warning now on Wyeth's Advil (ibuprofen) reads "ask a doctor before use" if the consumer has heart disease.

The requested labeling change also expands on ulcer warning language. Existing Aleve labeling refers to stomach bleeding as part of an alcohol warning, while ibuprofen products carry a statement that "taking more than recommended may cause stomach bleeding."

"This product contains a nonsteroidal anti-inflammatory drug (NSAID) which may cause stomach bleeding," the requested warning states.

The section lays out bulleted factors that increase the chances of a bleed, including age, preexisting ulcers and use of blood thinning agents, steroids or other NSAIDs (identified by ingredient names). Other factors include drinking three or more alcoholic beverages or taking the NSAID product beyond directed duration or dose.

Allergy warnings are revised under the request to add language specifying that people allergic to aspirin may have a reaction to the product. Early symptoms of Stevens-Johnson Syndrome such as skin reddening, rash and blisters are added to the current reaction list that includes hives and asthma.

FDA's new pediatric label template includes the revised adult warnings as well as pediatric-specific warnings "because such products are sometimes used by adults who cannot take solid oral dosage forms," the agency says.

Firms have 30 days to submit revisions and a six-month deadline to implement the changes, according to FDA.

Requested OTC NSAID Labeling Includes Cardiac Risk, Front Panel Changes

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