Acetaminophen products sold in stick packs and sachets must carry warnings about the risk of liver injury by April 29, 2010, a technical amendment to the final rule for internal analgesics says.

FDA is requiring manufacturers to use the warning despite limited space and industry protests, and it will affect products such as some of Novartis' Theraflu Warming Relief line, some Bayer Healthcare Alka-Seltzer Plus products and individually wrapped servings of two-tablet doses of Tylenol from McNeil Consumer Healthcare.

The sachet/stick pack warning is one of several issues FDA clarifies in a technical amendment to the final rule for organ-specific warnings on internal analgesics in the OTC monograph. The agency published the amendment in the Nov. 25 Federal Register.

FDA posted the final rule April 29, 2009, changing the required warnings for acetaminophen and non-steroidal anti-inflammatory drugs (¹ Also see "FDA Expands Acetaminophen, NSAID Labeling Beyond Tentative Final Rule" - Pink Sheet, 4 May, 2009.).

Warnings on immediate containers such as sachets and stick packs are important because "consumers may routinely remove these packages from the outer carton and, therefore, fail to see the liver injury and stomach bleeding warning if they are only printed on the carton," FDA says in the technical amendment.

By requiring the stick pack/sachet warning, FDA refuses a request from manufacturers.

FDA acknowledged requests that the agency should exempt certain immediate containers from the labeling requirement because of limited space, but disagrees, saying stick packs and sachets have "adequate space to accommodate the required warnings."

The agency makes some concessions to manufacturers, as requested by the Consumer Healthcare Products Association (² "The Tan Sheet" Sept. 7, 2009).

FDA acknowledged liver injury and stomach bleeding warnings for acetaminophen-containing products do not need to appear on individual blister pack cells because of limited space, as CHPA requested.

The agency clarifies manufacturers can place the warning on the blister card in a single location, "as long as the warning stays intact and readable when the drug product is removed from the blister card."

FDA also agrees with CHPA's recommendation to provide optional warning language for combination drugs that include acetaminophen.

Originally, FDA said all acetaminophen-containing products must include a warning that severe liver damage may occur if consumers take more than the maximum number of daily dosage units in 24 hours because they would exceed the daily amount of acetaminophen.

However, CHPA noted that some combination drugs limit doses because of ingredients other than acetaminophen. As a result, if consumers take the maximum daily dose of a combination product they may consume significantly less than the daily maximum for acetaminophen.

In those cases, FDA says the warning can say, "Severe liver damage may occur if you take more than the [insert maximum number of daily dosage units] in 24 hours, which is the maximum daily amount for this product."

Finally, FDA clarifies products with acetaminophen introduced within a year before the final rule's effective date - April 29, 2010 - must include a "see new warnings" flag for at least one year from the launch date.

Products launched after the effective date do not need the new warnings flag.

FDA maintains the rule will not have a "significant economic impact on a substantial number" of businesses.

Acetaminophen marketers could face more burdensome restrictions down the road, including removing certain doses from the market, if FDA follows the advice of an advisory panel convened in April to discuss ways to reduce the risk of hepatotoxicity related to the ingredient (³ Also see "Lower Acetaminophen Doses Recommended Despite Cost Impact, Lack Of Data" - Pink Sheet, 6 July, 2009.).

- Elizabeth Crawford ( ⁴ e.crawford@elsevier.com )

FDA Requires Liver Injury Warning On Acetaminophen Stick Packs, Sachets

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