FDA proposes an alternative statement for OTC drug makers to use in a required label warning for acetaminophen-containing products to explain when the ingredient can cause severe liver damage.

In a July 3 draft guidance, the agency says it will allow some acetaminophen products to warn that “severe liver damage may occur if you take more than 4,000 mg of acetaminophen in 24 hours.” FDA previously required firms to warn on product labels that severe liver damage may occur if a consumer exceeds the maximum daily dose of a product in 24 hours.

The proposed change seeks to clarify potential confusion for consumers about the level of acetaminophen that can pose a threat, FDA says in the guidance. The alternative warning language aims to link hepatotoxicity to the maximum amount of acetaminophen, not the overall product.

Liver Warning Language

Labels for all OTC acetaminophen-containing products must state, “Severe liver damage may occur if you take,” followed by one of these statements:

(Original proposed language that remains appropriate for some acetaminophen products) “More than [insert maximum number of daily dosage units] in 24 hours, which is the maximum daily amount [optional: “for this product”]”
(Proposed alternative language for the warning on some acetaminophen products) “More than 4,000 mg of acetaminophen in 24 hours”

All product labels also must include these warnings about potential liver damage:

“With other drugs containing acetaminophen
3 or more alcoholic drinks every day while using this product”

The agency says the original warning language could mislead consumers to believe that hepatotoxicity is associated with less than 4 grams of acetaminophen a day if the maximum daily dose for an acetaminophen product contained less than the maximum daily dose for the ingredient.

“Directions for use can result in a maximum daily dose of acetaminophen that is less than 4,000 mg for a variety of reasons,” the draft guidance says.

For example, the maximum daily dose for Johnson & Johnson business McNeil Consumer Healthcare’s Extra Strength Tylenol is six pills, or 3 grams of acetaminophen, substantially lower than the maximum daily amount of the ingredient Also see "McNeil Lowers Recommended Maximum Dose For Extra Strength Tylenol" - Pink Sheet, 1 August, 2011..

In addition, the indication for combination products, such as an acetaminophen-diphenhydramine sleep aid and internal analgesic product, limits the amount of acetaminophen in the maximum 24-hour dose to less than 4 grams, FDA says.

With the guidance, “FDA has formally recognized that the maximum labeled doses of all [acetaminophen-containing] products will not cause liver injury,” said Barb Kochanowski, VP of regulatory and scientific affairs at the Consumer Healthcare Products Association.

Kochanowski added the draft guidance is good news for the industry because it allows manufacturers to better clarify under what dosing situations a consumer likely could experience an adverse event. She encouraged firms to reexamine their labeling in light of the draft guidance.

Alternative Warning Limited

However, not all products qualify for the alternative language, FDA says in the guidance.

Only products for adults that have a maximum daily dose of less than 4 grams of acetaminophen may use the alternative warning language, FDA says. Products labeled for children younger than 12 years or for adults and children 12 years and older must use the old warning language.

Specifically, products for children younger than 12 must warn that severe liver damage may occur if a child takes more than five doses in 24 hours, rather than more than the maximum number of daily doses for a particular product. Likewise, products for older children and adults must specify hepatotoxicity risks based on the different maximum daily dose for each age group, FDA says.

In addition to warning about the risk of liver damage due to overdose, products must warn consumers that severe liver damage may occur if they take more than one product containing acetaminophen simultaneously or if they consume three or more alcoholic drinks daily while taking acetaminophen, according to a final rule issued in 2009 that took effect April 29, 2010 Also see "FDA Expands Acetaminophen, NSAID Labeling Beyond Tentative Final Rule" - Pink Sheet, 4 May, 2009..

Firms also must clearly highlight the presence of acetaminophen in products and label products as non-steroidal anti-inflammatory drugs, which include aspirin, ibuprofen, naproxen and ketoprofen, and print liver and stomach bleeding warnings on the outer carton and immediate container of all NSAIDs or acetaminophen-containing products, according to FDA guidelines.

The agency expanded these requirements to acetaminophen products sold in stick packs and sachets in a technical amendment to the final rule published later in 2009 Also see "FDA Requires Liver Injury Warning On Acetaminophen Stick Packs, Sachets" - Pink Sheet, 30 November, 2009..

FDA Clarifies Label Warning For Acetaminophen Liver Damage

More from United States

More from North America