FDA’s Suggested Acetaminophen Allergy Warning Tracks Industry Change
This article was originally published in The Tan Sheet
Executive Summary
The recommendation in a draft guidance covering single- and combination-ingredient acetaminophen products marketed under the tentative final monograph for internal analgesics mirrors a warning that some OTC manufacturers already are using on their products.
FDA suggests manufacturers add allergy warnings to labels of acetaminophen-containing OTC monograph products due to a risk of rare but serious and potentially fatal skin reactions, including Stevens-Johnson Syndrome.
The recommendation in a draft guidance published Nov. 28 in the Federal Register, covering single- and combination-ingredient acetaminophen products marketed under the tentative final monograph for internal analgesic, antipyretic, and antirheumatic drug products, mirrors a warning that some OTC manufacturers already are using.
Recommended Allergy Warning
In the draft guidance, FDA suggests adding this warning to product labels:
“Allergy alert: acetaminophen may cause severe skin reactions. Symptoms may include:
- skin reddening
- blisters
- rash
If a skin reaction occurs, stop use and seek medical help right away.”
The draft – “Recommended Warning for Over-the-Counter Acetaminophen-Containing Drug Products and Labeling Statements Regarding Serious Skin Reactions” – says the language should appear in the “Warnings” section of a product’s Drug Facts label, under an “Allergy Alert” subhead to be added directly following the existing “Liver Warning.”
Because the language is not part of required labeling on the TFM, FDA describes its regulatory approach by saying it “does not intend to object” to adding the warning to product labels. The agency also notes that “alternative warning language … may otherwise misbrand the product.”
The draft follows FDA’s August 2013 Drug Safety Communication stating that use of acetaminophen has been associated with a risk of skin reactions including toxic epidermal necrolysis and acute generalized exanthematous pustulosis as well as SJS. The DSC said FDA would work with manufacturers of acetaminophen OTCs to add the warning (Also see "Industry News Roundup" - Pink Sheet, 25 Nov, 2014.).
The warning language is identical to an alert the Consumer Healthcare Products Association suggested following FDA’s announcement about the skin reaction risks.
Jay Sirois, CHPA’s director of regulatory and scientific affairs, said the trade group made the recommendation in a February 2014 letter to advise FDA of its members’ efforts to warn consumers of the risks.
“We let [FDA] know that although the monograph doesn't include the warning language about these skin reactions, a number of our members have already added a warning, or planned to provide information,” Sirois said in an interview.
According to product labels available on FDA’s website, the allergy alert is included on labels for some single-ingredient acetaminophen OTCs that include changes approved this year.
CHPA has not determined the number of its members already using the skin allergy warning. The organization plans to meet with members before the end of the year and submit comments to FDA on the draft guidance.
NDA OTCs Already Adding Warning
FDA’s Center for Drug Evaluation and Research notes in the draft that a review of medical literature and the agency's adverse event reporting system revealed 107 cases of those serious reactions from 1969 to 2012, citing acetaminophen as a “probable” or “possible” cause of the conditions, which included 67 hospitalizations and 12 deaths.
“These skin reactions can occur with the first-time use of acetaminophen or at any time while it is being taken,” FDA notes. “FDA advised health care professionals to be aware of this rare risk and consider acetaminophen, along with other drugs already known to have such an association, when assessing patients with potentially drug-induced skin reactions.”
FDA says following the 2013 DSC, to firms marketing acetaminophen-containing Rx drugs and OTCs marketed under new drug applications it submitted letters “requiring in some cases and requesting in others that the [allergy alert] language … be included on the labeling for all products.”
The agency adds that “most of the requested labeling changes have been made by the relevant manufacturers.”
Potential adverse effects from acetaminophen use in children, particularly overdosing, also have been of concern.
In October, the agency released draft guidance on pediatric acetaminophen products, recommending OTC drug firms include appropriate dosage devices with liquid acetaminophen pediatric products and add flow restrictors to prevent overdosing (Also see "Draft Guidance Drills Down With Details To Cut Pediatric Acetaminophen Overdose Risk" - Pink Sheet, 8 Oct, 2014.).
However, even then FDA noted many manufacturers already had standardized the concentration of infants' and children's acetaminophen liquids to prevent dosing errors, following a 2011 FDA Nonprescription Drugs Advisory committee recommendation.
The deadline for comments on the acetaminophen labeling draft guidance is Jan. 27.