[Federal Register Volume 79, Number 229 (Friday, November 28, 2014)]
[Notices]
[Pages 70879-70880]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-28086]


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

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; 
Draft Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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

SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a draft guidance for industry entitled ``Recommended 
Warning for Over-the-Counter Acetaminophen-Containing Drug Products and 
Labeling Statements Regarding Serious Skin Reactions.'' The draft 
guidance is intended to inform manufacturers, members of the medical 
and scientific community, and other interested persons that at this 
time we do not intend to object to 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a warning as described in the draft guidance alerting consumers that 
the use of acetaminophen may cause severe skin reactions.

DATES: Although you can comment on any guidance at any time (see 21 CFR 
10.115(g)(5)), to ensure that the Agency considers your comment on this 
draft guidance before it begins work on the final guidance, submit 
either electronic or written comments on the draft guidance by January 
27, 2015.

ADDRESSES: 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, 10903 New Hampshire Ave., Bldg. 
51, Rm. 2201, 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.
    Submit electronic comments on the guidance to http://www.regulations.gov. Submit written comments to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Sudha Shukla, 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, 301-796-3110, [email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a draft 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 at any time while it 
is being taken. 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 the announcement, FDA stated that it planned to require 
manufacturers of acetaminophen-containing prescription

[[Page 70880]]

drug products to include a warning statement on the product labels to 
address the risk of serious skin reactions and that it would request 
the same warning be added by manufacturers of OTC acetaminophen-
containing drug products marketed under an approved application. In the 
fall of 2013, FDA sent letters to manufacturers holding new drug 
applications (NDA) and abbreviated new drug applications (ANDA) 
requiring in some cases and requesting in others that the language 
recommended below be included on the labeling for all products (both 
prescription and OTC) containing acetaminophen marketed under NDAs and 
ANDAs. At this time, most of the requested labeling changes have been 
made by the relevant manufacturers.
    FDA also indicated that it planned to encourage manufacturers of 
acetaminophen-containing drug products marketed under the Tentative 
Final Monograph for Internal Analgesic, Antipyretic, and Antirheumatic 
Drug Products for Over-the-Counter Human Use, published in the Federal 
Register (53 FR 46204, November 16, 1988) to similarly add a warning 
about serious skin reactions to the product labels. As noted above, 
this draft guidance informs manufacturers, members of the medical and 
scientific community, and other interested persons that at this time we 
do not intend to object to the marketing of single- and combination-
ingredient, acetaminophen-containing, nonprescription (commonly 
referred to as OTC) drug products bearing a warning as described in the 
draft guidance alerting consumers that the use of acetaminophen may 
cause severe skin reactions.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the Agency's current thinking on the 
recommended warning for OTC acetaminophen-containing drug products and 
labeling statements regarding serious skin reactions. It does not 
create or confer any rights for or on any person and does not operate 
to bind FDA or the public. An alternative approach may be used if such 
approach satisfies the requirements of the applicable statutes and 
regulations.

II. Comments

    Interested persons may submit either electronic comments regarding 
this document to http://www.regulations.gov or written comments to the 
Division of Dockets Management (see ADDRESSES). It is only necessary to 
send one set of comments. Identify comments with the docket number 
found in brackets in the heading of this document. Received comments 
may be seen in the Division of Dockets Management between 9 a.m. and 4 
p.m., Monday through Friday, and will be posted to the docket at http://www.regulations.gov.

III. Paperwork Reduction Act of 1995

    Under the draft 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)).

IV. 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: November 21, 2014.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2014-28086 Filed 11-26-14; 8:45 am]
BILLING CODE 4164-01-P