Wyeth Says NSAID Risk Label May Confuse Consumers

Available evidence may not support a new FDA-requested NSAID cardiovascular risk warning for ibuprofen in an over-the-counter use context, according to Wyeth.

The statement "When using this product...taking longer than 10 days or more than the recommended dose may increase the risk of heart attack or stroke" is not consistent with much of the available medical literature, the Advil marketer said June 16.

FDA issued templates for a number of requested revisions to Drug Facts panels for OTC ibuprofen, naproxen and ketoprofen products in June 15 letters (see ¹ (Also see "Requested OTC NSAID Labeling Includes Cardiac Risk, Front Panel Changes" - Pink Sheet, 20 Jun, 2005.)). The agency announced in April it would seek more specific labeling language about cardiac and gastrointestinal risks for all NSAIDs (² (Also see "FDA Determines A “Class Effect” Is In Play For All NSAIDs" - Pink Sheet, 11 Apr, 2005.), p. 3).

Wyeth said that of 15 relevant ibuprofen studies, seven demonstrated no effect on CV risk, five suggested a benefit and three showed a possible increased risk.

Wyeth identified the six-month timeframe laid out by FDA for implementing revisions as the "biggest issue" raised by the agency's request, but also cited several points in the labeling language as areas of concern.

FDA asks firms to submit revisions within 30 days. Companies should enact the changes within six months; those unable to meet the deadline should discuss the timing with the agency, FDA notes.

Wyeth expects to submit revisions on deadline, but the implementation timing poses "a challenge, which we hope to mitigate following discussions with the FDA."

The firm currently is in the process of reviewing the revisions. However, upon initial consideration, Wyeth said some aspects of the label may create confusion for consumers.

"From a medical perspective, some clarifications of wording may be required, because some of the language may be problematic for consumer understanding," Wyeth maintained.

For example, the language needs to clarify differences in dosing and duration between OTC and Rx NSAIDs, the firm said.

In addition to cardiovascular risk language, the NSAID marketer also pointed to the use of the phrase "feel faint" among "signs of stomach bleeding" as potentially problematic because faintness can be a symptom of unrelated conditions.

One challenge to implementation is the requested addition of "(NSAID)" following the active ingredient name on the principal display panel (PDP), Wyeth said.

The firm said it is "struggling to find room" for additional information, given existing PDP requirements.

Furthermore, ingredient information should remain on the Drug Facts panel, Wyeth contended.

"Conceptually, Drug Facts labeling was designed to provide a consistent and clearly defined location for product ingredient information," the firm stated, adding that there is no evidence the format is "deficient in conveying ingredient information."

The OTC industry has traditionally opposed FDA attempts to impose changes to the PDP.

However, even on the Drug Facts panel, the use of the term "NSAID" may confuse consumers, said Wyeth. Many consumers may have trouble identifying which prescription and OTC drugs are part of the class, the firm asserted.

The company does not yet have an estimate of the potential cost of the new label changes.

The revisions apply to all OTC adult and pediatric ibuprofen, ketoprofen and naproxen products. Any package inserts should reflect the changes, FDA noted.

Other brands containing ibuprofen include McNeil's Motrin line and Sine-Aid IB , Ohm Labs' Ibuprohm , and Alterna's Elixsure . Also affected by the new label are Bayer's Aleve (naproxen) and Actron (ketoprofen) and Wyeth's Orudis KT (ketoprofen).

McNeil, Bayer and Wyeth all stressed the safety of their products under approved OTC usage regimens and cited their intentions to comply with FDA requirements. McNeil and Bayer also are reviewing the revisions.