NSAID Label Changes Revised By FDA; Compliance Date Extended

FDA updates to OTC labeling requirements respond to industry requests. July 18 letter from the agency revises heart risk warnings.

FDA has deleted the part of its recommended heart risk warning for NSAIDs that discourages use for "longer than 10 days or more than the recommended dose."

The agency has edited the new labeling it is seeking for OTC ibuprofen, naproxen and ketoprofen in response to requests by industry.

Heart risk warnings initially specified in FDA's June 15 supplemental labeling request have been superseded by a July 18 request. The changes relate to both the "Drug Facts" section and principal display panel of labels.

The new language states, "long term continuous use" may increase the risk of heart attack or stroke.

The 10-day cardiovascular risk warning was one of the primary issues Advil marketer Wyeth cited among its concerns with the earlier labeling request.

Industry stakeholders, including Wyeth, have expressed the position that the language did not accurately reflect existing trial data.

The agency issued the original supplemental request letters and new drug facts panel templates in response to NSAID class concerns that surfaced following the withdrawal of Merck's Vioxx .

The July 18 request includes other departures from the agency's ¹ June 15 templates.

FDA has also modified the language cautioning against the products' concomitant use with other NSAIDs.

The earlier templates warned, "Do not use... with any other drug containing an NSAID (prescription or nonprescription). Ask a doctor or pharmacist before using with other drugs if you are not sure."

The new version moves the warning from the "Do not use" section, instead directing consumers to "Ask a doctor or pharmacist…before use with any other drug containing an NSAID (prescription or nonprescription)."

Pediatric labeling now includes the bolded statement: "This product does not contain directions or complete warnings for adult use" under the "Directions" heading.

Consequently, adult-oriented warnings about possible stomach bleeding in users ages 60 or older and in those consuming three or more alcoholic drinks daily no longer appear on the pediatric labeling.

Also dropped from the pediatric template is a pregnancy/breast-feeding warning. In addition, the word "user" in the standard headings of the pediatric labeling has been changed to "child."

FDA previously included the adult warnings on children's products out of concern for older consumers who may take pediatric liquid products because they have difficulty swallowing solid oral dosage forms.

The updated labeling continues to request use of the term "NSAID" in parentheses on the principal display panel (PDP). However, the agency has added some flexibility about print size and location.

FDA's preceding request stated that "(NSAID)" should appear after the name of the active ingredient on the PDP.

The new labeling allows "(NSAID)" to follow either the name of the NSAID ingredient or "the terms that describe its general pharmacological category(ies) or principal intended actions(s)."

The font size should be "equal to or larger than that in the currently approved labeling for these statements." Previously FDA asked that the term be at least one-half the size of the largest print on the PDP.

The agency continues to request that "the word '(NSAID)' should appear highlighted in either fluorescent or color contrast or in bold type."

In the letter, FDA reminds NSAID marketers that the revisions should be reflected in any package inserts as well.

Prior approval supplements must be submitted for any deviations from the amended templates, FDA asserts.

The agency requests firms to submit the latest revisions through a "changes being effected" supplement within 30 days. The changes should be implemented within six months.

- Jessica Lake