Notice to Industry: Draft Guidance for Over-the-Counter Products that Contain Acetaminophen

The U.S. Food and Drug Administration (FDA) today issued draft guidance¹ to manufacturers of over-the-counter (OTC) acetaminophen products, providing alternative language to the liver warning section of the product’s labeling.

In certain instances, FDA now will allow manufacturers to state the maximum daily dosage as 4,000 mg in a 24-hour period for the liver warning. This language can be used instead of specifying the maximum number of tablets or dosage units for the product, as has been required.

The alternative language states:

“Liver warning: This product contains acetaminophen. Severe liver damage may occur if you take • more than 4,000 mg of acetaminophen in 24 hours • with other drugs containing acetaminophen • 3 or more alcoholic drinks every day while using this product.”

In 2009, FDA published a final rule to require specific language on the labeling of all OTC drugs containing acetaminophen to warn of the risk of liver damage. This regulation, effective April 29, 2010, is listed in the Code of Federal Regulations at 21 CFR 201.326².

The regulation requires that acetaminophen-containing OTC products include a warning on the labeling stating that exceeding the maximum daily amount of acetaminophen (currently 4,000 mg) is associated with severe liver damage.

Currently, manufacturers must use specific language referring to the product’s maximum dosage in terms of dosage units, or total number of tablets that should not be exceeded in a 24-hour period. For example, for 500 mg tablets, the label has to read, “Severe liver damage may occur if you take more than 8 tablets in 24 hours, which is the maximum daily amount for this product.”

However, some OTC products that contain acetaminophen have directions for use that result in a maximum daily dose of acetaminophen that is less than 4,000 mg. As a result, stating the product’s maximum amount in tablets or dosage units instead of milligrams could be misinterpreted to suggest that consumers might suffer severe liver damage at a dosage much lower than the 4,000 mg maximum daily amount.

In certain instances, the alternate language will give manufacturers another option to properly characterize the risk of the liver warning requirement, and ensure the appropriate dosing of OTC acetaminophen-containing products.