FDA Proposes Skin Reaction Label Warning for Tylenol, Other Drugs Containing Acetaminophen

Federal drug regulators are calling for Tylenol and other acetaminophen-based drugs to carry warnings about the risk of dangerous skin reactions, following years of reports and scientific data linking the popular pain killer to the development of Stevens-Johnson Syndrome.

The U.S. Food and Drug Administration (FDA) issued a proposed administrative order (PDF) on June 14, which would affect the over-the-counter labels on drugs containing acetaminophen. The proposed order would alert consumers to the risks of allergic skin reactions that could result in skin reddening, blisters, and rash.

The warning comes after a long history of data linking acetaminophen to a devastating skin condition known as Stevens-Johnson Syndrome (SJS), which can result in painful blisters, severe rash and can cause the skin to separate from the body. When the skin lesions affect more than 30% of the body, the condition is typically referred to as toxic epidermal necrolysis (TEN), which often results in the need for treatment in a hospital Intensive Care Unit (ICU) or Burn Unit.

Prior studies have linked the development of Stevens-Johnson syndrome to anticonvulsants, antibiotics and non-steroidal anti-inflammatory drugs (NSAIDS), but acetaminophen has always been one of the most widely cited causes.

In 2014, the FDA issued a draft guidance calling for new label warnings for Tylenol and other acetaminophen drugs due to the risks of SJS and TEN. This proposed order would make that guidance a requirement.

“Today’s actions represent important milestones in FDA’s implementation of new authorities provided by Congress as part of OTC Monograph Reform,” Dr. Theresa Michele, M.D., director of the Office of Nonprescription Drugs in FDA’s Center for Drug Evaluation and Research, said in a press release. “Today’s proposed order helps to ensure the safety and effectiveness of OTC drugs in our marketplace.”

The warning would appear in the monograph of all over-the-counter drug products containing acetaminophen, including Tylenol.

The FDA also released an acetaminophen scientific review (PDF), which lays out the agency’s reasoning for requiring the new label warnings.

An updated review of reports submitted to the FDA identified 25 cases of SJS/TEN linked to acetaminophen use between February 2012 and June 2021. In addition, there were three reported cases of acute generalized exanthematous pustulosis (AGEP), which is a rare form of skin hypersensitivity adverse reaction, which can cause an outbreak of pustules on the skin, as well as fever. However, it is usually not life-threatening.

The FDA is accepting public comment on the proposed acetaminophen label warning changes until July 29, 2024. Comments must be submitted electronically to https://dps.fda.gov/omuf with the proposed order ID number: OTC000035.