Document ID: FDA-2014-D-1862-0007
Agency: fda
Document Type: Notice
Title: Recommended Warning for Over-the-Counter Acetaminophen-Containing Drug Products and Labeling Statements Regarding Serious Skin Reactions; Guidance for Industry; Availability
Posted Date: 2017-01-11T05:00Z

[Federal Register Volume 82, Number 7 (Wednesday, January 11, 2017)]
[Notices]
[Pages 3332-3333]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-00375]

-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2014-D-1862]

Recommended Warning for Over-the-Counter Acetaminophen-Containing 
Drug Products and Labeling Statements Regarding Serious Skin Reactions; 
Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a guidance for industry entitled ``Recommended Warning 
for Over-the-Counter Acetaminophen-Containing Drug Products and 
Labeling Statements Regarding Serious Skin Reactions.'' This guidance 
is intended to inform manufacturers, members of the medical and 
scientific community, and other interested persons that at this time 
FDA does not intend to take action against the marketing of single- and 
combination-ingredient, acetaminophen-containing, nonprescription 
(commonly referred to as over-the-counter (OTC)) drug products bearing 
a warning as described in the guidance alerting consumers that the use 
of acetaminophen may cause severe skin reactions.

DATES: Submit either electronic or written comments on Agency guidances 
at any time.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on http://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2014-D-1862 for ``Recommended Warning for Over-the-Counter 
Acetaminophen-Containing Drug Products and Labeling Statements 
Regarding Serious Skin Reactions; Guidance for Industry.'' Received 
comments will be placed in the docket and, except for those submitted 
as ``Confidential Submissions,'' publicly viewable at http://www.regulations.gov or at the Division of Dockets Management between 9 
a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on http://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. If you do not 
wish your name and contact information to be made publicly available, 
you can provide this information on the cover sheet and not in the body 
of your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other

[[Page 3333]]

applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.
    Submit written requests for single copies of this guidance to the 
Division of Drug Information, Center for Drug Evaluation and Research, 
Food and Drug Administration, 10001 New Hampshire Ave., Hillandale 
Building, 4th Floor, Silver Spring, MD 20993-0002. Send one self-
addressed adhesive label to assist that office in processing your 
requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Emily Baker, Office of Unapproved 
Drugs and Labeling Compliance, Center for Drug Evaluation and Research, 
Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, 
MD 20993-0002, 301-796-7524, Emily.Baker@fda.hhs.gov.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Recommended Warning for Over-the-Counter Acetaminophen-
Containing Drug Products and Labeling Statements Regarding Serious Skin 
Reactions.'' Acetaminophen, included in many prescription and OTC 
products, is a common active ingredient indicated to treat pain and 
reduce fever. On August 1, 2013, FDA issued a Drug Safety Communication 
(DSC) informing the public that use of acetaminophen has been 
associated with a risk of rare but serious skin reactions.\1\ These 
skin reactions, including Stevens-Johnson Syndrome, toxic epidermal 
necrolysis, and acute generalized exanthematous pustulosis, can be 
fatal.
---------------------------------------------------------------------------

    \1\ FDA Drug Safety Communication: FDA warns of rare but serious 
skin reactions with the pain reliever/fever reducer acetaminophen. 
http://www.fda.gov/Drugs/DrugSafety/ucm363041.htm.
---------------------------------------------------------------------------

    The DSC explained that reddening of the skin, rash, blisters, and 
detachment of the upper surface of the skin can occur with the use of 
drug products that contain acetaminophen. These skin reactions can 
occur with the first-time use of acetaminophen or even if acetaminophen 
has been used in the past without any problems. 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 
also advised that anyone who develops a skin rash or reaction while 
using acetaminophen or any other pain reliever/fever reducer should 
stop taking the drug and seek medical attention right away. 
Furthermore, the announcement advised that anyone who has experienced a 
serious skin reaction when taking acetaminophen in the past should not 
take the drug again and should contact their health care professional 
to discuss alternative pain relievers/fever reducers.
    In response to FDA's letters to manufacturers holding new drug 
applications and abbreviated new drug applications, most manufacturers 
of acetaminophen-containing prescription and OTC drug products marketed 
under an approved application now include a warning statement on their 
product labels to address the risk of serious skin reactions. FDA 
recommends that manufacturers of all acetaminophen-containing OTC drug 
products (both single- and combination-ingredient acetaminophen 
products) marketed under the Tentative Final Monograph (TFM) for 
Internal Analgesic, Antipyretic, and Antirheumatic Drug Products 
include in labeling the language recommended in this guidance to warn 
consumers that acetaminophen may cause severe skin reactions. At this 
time, FDA does not intend to take action against the marketing of 
single- and combination-ingredient, acetaminophen-containing, OTC drug 
products bearing the recommended allergy warning that are otherwise 
marketed in compliance with the TFM and applicable regulations.
    In the Federal Registerof November 28, 2014 (79 FR 70879), FDA 
published a draft guidance entitled ``Recommended Warning for Over-the-
Counter Acetaminophen-Containing Drug Products and Labeling Statements 
Regarding Serious Skin Reactions.'' See: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm424898.pdf. 
The November 2014 draft guidance gave interested persons an opportunity 
to submit comments through January 27, 2015. We have made changes to 
the guidance in response to comments received and have added labeling 
information about products that contain both acetaminophen and aspirin.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
current thinking of FDA on the recommended warning for OTC 
acetaminophen-containing drug products and labeling statements 
regarding serious skin reactions. It does not establish any rights for 
any person and is not binding on FDA or the public. You can use an 
alternative approach if it satisfies the requirements of the applicable 
statutes and regulations.

II. Paperwork Reduction Act of 1995

    Under the guidance, manufacturers may add to their drug product 
labeling a warning statement supplied by FDA that pertains to 
acetaminophen to address the risk of serious skin reactions. Inclusion 
of the warning statement on the labels for these drug products would be 
exempt from review by the Office of Management and Budget under the 
Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520) because the 
public disclosure of information originally supplied by the Federal 
government to the recipient for the purpose of disclosure to the public 
is not included within the definition of ``collection of information'' 
(see 5 CFR 1320.3(c)(2)).

III. Electronic Access

    Persons with access to the Internet may obtain the document at 
either http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or http://www.regulations.gov.

    Dated: January 5, 2017.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2017-00375 Filed 1-10-17; 8:45 am]
 BILLING CODE 4164-01-P