Recommended Statement for Over-the-Counter Aspirin-Containing Drug Products Labeled With Cardiovascular Related Imagery Guidance for Industry

Administrative guidance, not enacted legislation. This captured publisher edition preserves the listed document and attachments; later developments are not independently consolidated.

Recommended Statement for Over-
the-Counter Aspirin-Containing
Drug Products Labeled With
Cardiovascular Related Imagery
Guidance for Industry
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
November 2017
Compliance

Recommended Statement for Over-
the-Counter Aspirin-Containing
Drug Products Labeled With
Cardiovascular Related Imagery
Guidance for Industry
Additional copies are available from:
Office of Communications, Division of Drug Information
Center for Drug Evaluation and Research
Food and Drug Administration
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor
Silver Spring, MD 20993-0002
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353
Email: druginfo@fda.hhs.gov
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
November 2017
Compliance

Contains Nonbinding Recommendations
i
TABLE OF CONTENTS
I. INTRODUCTIONAND SCOPE...................................................................................... 1
II. BACKGROUND ............................................................................................................... 1
III. DISCUSSION AND POLICY .......................................................................................... 2

Contains Nonbinding Recommendations
Recommended Statement for Over-the-Counter Aspirin-
Containing Drug Products Labeled With Cardiovascular
Related Imagery
Guidance for Industry1
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on
this topic. 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.
To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the
title page.
I. INTRODUCTION AND SCOPE
This guidance applies to single-ingredient aspirin, buffered aspirin, and aspirin in combination
with an antacid, labeled with cardiovascular related imagery marketed under the Tentative Final
Monograph (TFM) for Internal Analgesic, Antipyretic, and Antirheumatic (IAAA) Drug
Products for OTC Human Use (53 FR 46204, November 16, 1988).2 FDA is aware that some
over-the-counter (OTC) aspirin drug products are marketed with cardiovascular related images,
such as heart symbols, which suggest or imply that the products are intended for use in the
prevention of cardiovascular events. Secondary prevention of cardiovascular events is permitted
as an indication for aspirin in professional labeling (21 CFR 343.80). This guidance is intended
to promote the safe use of OTC aspirin drug products by encouraging drug manufacturers,
packagers, and labelers marketing aspirin drug products with cardiovascular related imagery to
include a statement that reminds consumers to talk to their doctor or other healthcare provider
before using aspirin for the professional indication of secondary prevention of cardiovascular
events.
In general, FDA’s guidance documents do not establish legally enforceable responsibilities.
Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only
as recommendations, unless specific regulatory or statutory requirements are cited. The use of
the word should in Agency guidances means that something is suggested or recommended, but
not required.
II. BACKGROUND
Aspirin is a common active ingredient in many prescription and OTC drug products. Most OTC
aspirin drug products are currently marketed pursuant to the TFM for IAAA Drug Products (53
1 This guidance has been prepared by the Office of Unapproved Drugs and Labeling Compliance in the Center for
Drug Evaluation and Research (CDER) at the Food and Drug Administration.
2 See https://www.gpo.gov/fdsys/pkg/FR-1988-11-16/pdf/FR-1988-11-16.pdf.

Contains Nonbinding Recommendations
2
FR 46206, November 16, 1988) for the temporary relief of minor aches and pains associated
with a cold, headache, backache, toothache, premenstrual and menstrual cramps; minor pain of
arthritis; and reduction in fever.2
In addition to the OTC conditions of use in the IAAA TFM, FDA regulations at § 343.80 also
contain professional labeling about cardiovascular uses of aspirin directed at healthcare
practitioners (63 FR 56802, October 23, 1998). The cardiovascular indications for aspirin under
professional labeling include reducing the risk of a second heart attack or stroke in patients who
have already experienced a cardiovascular or cerebrovascular event or for patients with existing
coronary artery disease such as angina or a history of a coronary bypass or coronary angioplasty.
However, such long-term aspirin therapy has a number of side effects, such as stomach bleeding,
bleeding in the brain, kidney failure, and other kinds of strokes.
In the IAAA TFM, FDA proposed a labeling statement recommending that consumers consult a
physician about the professional indications of aspirin, because of the potential side effects of
long-term aspirin therapy (53 FR 46204, November 16, 1988).2
In addition, FDA published a proposed rule on October 20, 1993, that would require OTC drug
products that contain aspirin, buffered aspirin, or aspirin in combination with an antacid to bear a
statement advising consumers to consult a physician before taking these products for
cardiovascular uses (58 FR 54224, October 20, 1993).3 However, this proposed rule has not
been finalized.
III. DISCUSSION AND POLICY
After publication of the professional labeling regulation for aspirin, some OTC aspirin labels4
were modified to include cardiovascular related imagery (e.g., heart image, electrocardiography
graphic, stethoscope around a heart image). However, the final rule for IAAA products at §
343.80 authorizes labeling for cardiovascular events only in professional labeling directed to
healthcare professionals.
Because of the potential side effects associated with long-term aspirin therapy, FDA
recommends that any cardiovascular related imagery on OTC aspirin labels be accompanied by a
statement that reminds consumers to talk to their doctor or other healthcare provider before using
aspirin for the professional indication of secondary prevention of cardiovascular events. More
specifically, FDA does not intend to take action against manufacturers of single-ingredient
aspirin, buffered aspirin, and aspirin in combination with an antacid, marketed pursuant to the
TFM for IAAA Drug Products because the product label includes cardiovascular related imagery
such as the heart image, if the label also includes the following statement:
Talk to your doctor or other healthcare provider before using this product for your heart.
3 See https://cdn.loc.gov/service/ll/fedreg/fr058/fr058201/fr058201.pdf.
4 In this guidance, the term “label” means the written, printed, and graphic matter upon the immediate container and
upon the outside container or wrapper of the retail package of an OTC aspirin drug product. See section 201(k) of
the Federal Food, Drug, and Cosmetic Act.

Contains Nonbinding Recommendations
3
This recommended statement should appear in reasonable proximity to the cardiovascular related
imagery and with similar prominence in at least 6-point type size font on the principal display
panel (PDP).
This guidance does not address alternative language, other health imagery, or other
cardiovascular claims included on consumer directed label or labeling which may otherwise
misbrand the product.