[Federal Register Volume 61, Number 31 (Wednesday, February 14, 1996)]
[Proposed Rules]
[Pages 5912-5916]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-3323]




[[Page 5911]]

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Part VIII





Department of Health and Human Services





_______________________________________________________________________



Food and Drug Administration



_______________________________________________________________________



21 CFR Parts 201 and 369



Over-the-Counter Drug Products Containing Phenylpropanolamine; Required 
Labeling; Proposed Rule

  Federal Register / Vol. 61, No. 31 / Wednesday, February 14, 1996 / 
Proposed Rules   

[[Page 5912]]


DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 201 and 369

[Docket No. 95N-0060]


Over-the-Counter Drug Products Containing Phenylpropanolamine; 
Required Labeling

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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

SUMMARY: The Food and Drug Administration (FDA) is proposing new 
warning labeling for all over-the-counter (OTC) drug products 
containing phenylpropanolamine preparations (phenylpropanolamine 
bitartrate, phenylpropanolamine hydrochloride, and phenylpropanolamine 
maleate). Phenylpropanolamine is a sympathomimetic drug that is used in 
OTC weight control, cough-cold, nasal decongestant, and allergy drug 
products. The warnings will advise consumers not to take more than the 
recommended dose of phenylpropanolamine, not to take 
phenylpropanolamine with certain prescription drugs, and not to take 
phenylpropanolamine under certain conditions. The warnings will also 
advise consumers that they should not take a phenylpropanolamine drug 
product with any other drug product containing the ingredients 
phenylpropanolamine, phenylephrine, pseudoephedrine, or ephedrine, 
which are sympathomimetic drugs commonly found in allergy, asthma, 
cough-cold, nasal decongestant, and weight control drug products. These 
drugs could be harmful if taken together.

DATES: Submit comments on the proposed regulation by May 14, 1996. 
Written comments on the agency's economic impact determination by May 
14, 1996. FDA is proposing that any final rule based on this proposal 
be effective 6 months after the date of its publication in the Federal 
Register.

ADDRESSES: Written comments to the Dockets Management Branch (HFA-305), 
Food and Drug Administration, rm. 1-23, 12420 Parklawn Dr., Rockville, 
MD 20857.

FOR FURTHER INFORMATION CONTACT: William E. Gilbertson, Center for Drug 
Evaluation and Research (HFD-105), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-2304.

SUPPLEMENTARY INFORMATION:

I. Background

    In the Federal Register of September 9, 1976 (41 FR 38312), the 
Advisory Review Panel on OTC Cold, Cough, Allergy, Bronchodilator, and 
Antiasthmatic Drug Products (Cough-Cold Panel) recommended that 
phenylpropanolamine be classified in Category I (generally recognized 
as safe and effective, and not misbranded) for nasal decongestant use 
at adult oral dosages equivalent to the following phenylpropanolamine 
hydrochloride dosages: 25 milligrams (mg) every 4 hours (h) or 50 mg 
every 8 h, not to exceed 150 mg in 24 h (41 FR 38312 at 38420). The 
agency has allowed these dosages for phenylpropanolamine hydrochloride 
for OTC cough-cold use and is including these dosages in this proposal. 
The Federal Register of February 26, 1982 (47 FR 8466), the Advisory 
Review Panel on OTC Miscellaneous Internal Drug Products (Miscellaneous 
Internal Panel) recommended that phenylpropanolamine hydrochloride be 
classified as Category I for weight control use in adult oral dosages 
of 25 to 50 mg, not to exceed 150 mg daily. As discussed below, the 
agency has limited OTC phenylpropanolamine hydrochloride dosages for 
weight control to 75 mg daily and, based on its indication for use, is 
including that dosage in this proposal.
    After the Miscellaneous Internal Panel completed its report, the 
agency became award of studies indicating that certain dosages of 
phenylpropanolamine cause blood pressure elevation. These studies were 
discussed in the preamble to the advance notice of proposed rulemaking 
for OTC weight control drug products (47 FR 8466 through 8468). At that 
time, the agency specifically requested comments and information on the 
extent to which phenylpropanolamine induces or aggravates hypertension. 
The agency also stated that it would not allow any increase in OTC 
weight control dosages above those currently permitted: An immediate-
release dose of up to 37.5 mg and a time-release dose of up to 75 mg 
phenylpropanolamine, with the total daily dose not to exceed 75 mg in 
either case.
    Many comments were submitted in response to the agency's request 
for information concerning the safety of phenylpropanolamine. Some 
comments requested that phenylpropanolamine be removed from the OTC 
drug market because of its association with increased blood pressure 
and other adverse effects. Other comments contended that 
phenylpropanolamine is safe for OTC use.
    After preliminary evaluation of the information submitted by these 
comments, FDA determined that phenylpropanolamine produces hemodynamic 
effects (raises blood pressure), but that the data were inadequate to 
respond to the agency's safety concerns. Subsequently, in meetings with 
industry on December 2, 1983, and April 11, 1984, the agency discussed 
its requirements for adequate studies to address this concern about 
phenylpropanolamine (Refs. 1 and 2). The agency concluded that data 
were required to: (1) Determine if phenylpropanolamine plays any role 
in adverse events such as stroke or seizure and other serious adverse 
reactions that have been reported in association with this drug, and 
(2) provide information on other possible risk factors (e.g., age, 
hypertension, concomitant drug use, or disease conditions) associated 
with phenylpropanolamine use.
    In response to the agency's request for data and information, drug 
manufacturers submitted new dose-response studies designed to 
investigate the blood pressure effects of phenylpropanolamine. After 
reviewing all available information, FDA remains concerned about the 
possibility that phenylpropanolamine used in OTC drug products might 
increase the risk of hemorrhagic stroke (Ref. 3). The possible risk of 
stroke is suggested by a relatively small number of spontaneous reports 
(published and unpublished) of intracranial bleeding, typically in 
young, female users of phenylpropanolamine weight control drug 
products, and by the known ability of phenylpropanolamine to 
transiently increase blood pressure (Ref. 4). A possible mechanism of 
these reported events, if indeed they are caused by 
phenylpropanolamine, is an exaggerated hypertensive response, although 
in most cases no large elevation in blood pressure was detected in 
association with the hemorrhage. Based on the available data, the 
agency cannot rule out the possibility that phenylpropanolamine may 
increase the risk of stroke. This possible risk could be further 
increased if the recommended dose of phenylpropanolamine was 
inadvertently exceeded, e.g., taken from two products labeled for 
different uses.
    Because of these concerns, in 1994 the OTC drug industry initiated 
a large-scale, population-based epidemiologic study of the relationship 
between OTC phenylpropanolamine drug products and the incidence of 
hemorrhagic stroke (Ref. 5). However, the study is not expected to be 
completed until 1998. 

[[Page 5913]]
The agency believes this study will provide a sufficiently large data 
base to help determine whether the incidence of stroke associated with 
ingestion of phenylpropanolamine is greater than the spontaneous rate 
of stroke, i.e., the rate that would be expected to occur in a similar 
population not using the drug. The agency does not believe, however, 
based on information currently available, that phenylpropanolamine used 
in OTC weight control drug products represents a substantial public 
health risk. The agency, therefore, does not believe that it is 
necessary to remove phenylpropanolamine weight control drug products 
from the OTC market while additional data are being obtained.
    While this study is being conducted, the OTC drug industry has 
proposed additional labeling for OTC phenylpropanolamine weight control 
drug products to help ensure that their use is confined to adults and 
that the recommended dose is not exceeded (Ref. 6). Industry's proposal 
includes a new warning that states: ``If nervousness, dizziness, 
sleeplessness, palpitations, or headache occur, stop using this 
medication and consult your physician.'' The proposal also includes a 
new, separate drug interaction precaution that states:
    DRUG INTERACTION PRECAUTION: If you are taking a cough-cold or 
allergy medication containing any form of phenylpropanolamine, or 
any type of nasal decongestant, do not take this product. Do not 
take this product if you are taking any prescription drug, except 
under the advice and supervision of a physician. Do not use this 
product if you are presently taking a prescription monoamine oxidase 
inhibitor (MAOI) for depression or for two weeks after stopping use 
of an MAOI without first consulting a physician.

    In addition, the OTC drug industry's proposal includes a warning 
that states ``Persons between 12 and 18 are advised to consult their 
physician before using this product.'' The agency believes that people 
under 18 years of age should not use an OTC weight control drug product 
unless specifically directed by a doctor and is modifying that 
statement in Sec. 201.321(c)(1) of this proposal.
    In considering these proposals, the agency notes that the 
Miscellaneous Internal Panel stated that ingestion of 
phenylpropanolamine can be expected to cause vasoconstriction, 
bronchodilation, and tachycardia, because of its alpha and beta 
adrenergic effects. Large doses would be expected to cause anxiety, 
excitement, insomnia, headache, cardiac arrhythmias, convulsions, and 
circulatory collapse (47 FR 8466 at 8474). The Miscellaneous Internal 
Panel was concerned that a person might ingest a dose of 
phenylpropanolamine to reduce nasal congestion and another dose from a 
different product for weight control, and that the combined doses might 
have adverse effects. Accordingly, the Miscellaneous Internal Panel 
recommended a warning statement concerning this possibility on all drug 
products containing phenylpropanolamine, and included the following 
language in its monograph for OTC weight control drug products (47 FR 
8475): ``If you are taking a cough-cold or allergy medication 
containing any form of phenylpropanolamine, do not take this product.''
    Many manufacturers of OTC phenylpropanolamine weight control drug 
products have voluntarily included this warning in product labeling 
following publication of the Miscellaneous Internal Panel's report. 
However, the rulemakings for OTC phenylpropanolamine nasal decongestant 
and weight control drug products will not be completed until after the 
phenylpropanolamine epidemiologic study is completed and the data 
assessed. The agency believes that implementation of these warnings 
should not await the completion of these monograph proceedings, but 
that a warning should be required on all OTC phenylpropanolamine drug 
products at this time.
    Similarly, because phenylpropanolamine is a sympathomimetic drug 
(affects the central nervous system, cardiovascular system, and basal 
metabolic rate), the agency believes that phenylpropanolamine should 
not be used simultaneously with other sympathomimetic drugs, e.g., 
pseudoephedrine, ephedrine, or phenylephrine, that would have similar 
effects on the body. The agency believes that labeling OTC 
phenylpropanolamine drug products should advise consumers to avoid use 
while they are using any other sympathomimetic drugs.
    FDA concurs with the industry's labeling proposals but has 
broadened the labeling to include other sympathomimetic drug 
ingredients and the kinds of products in which they are used. FDA has 
sufficient concern that adverse reactions could occur from taking 
phenylpropanolamine in different drug products or from combining 
sympathomimetic drugs; thus, this information should be included in the 
``Warnings'' statement.
    In the final rule for OTC nasal decongestant drug products, 
published in the Federal Register of August 23, 1994 (59 FR 43386), the 
agency included a drug interaction precaution statement regarding the 
use of sympathomimetic drugs in combination with MAOI drugs. That 
statement (in Sec. 341.80(c)(1)(i)(D)) (21 CFR 341.80(c)(1)(i)(D) 
includes certain conditions (i.e., depression, psychiatric or emotional 
conditions, Parkinson's disease) for which MAOI drugs are used. A 
similar statement (but not listing Parkinson's disease) appears in 
Sec. 341.80(c)(1)(ii)(D) for products labeled for children under 12 
years of age. Products labeled for both adults and children under 12 
years of age use the statement in paragraph (c)(1)(i)(D). In addition, 
the statement instructs consumers to consult a health professional if 
they are uncertain that they are using an MAOI drug. The agency is 
proposing a shortened version of this precaution statement in the 
labeling approach used in this current proposal. The agency is asking 
for comments on how to further shorten or improve this precaution 
statement. If a shortened version is eventually incorporated in a final 
rule, the agency will revise Sec. 341.80 accordingly at that time.

II. References

    The following information has been placed on display in the Dockets 
Management Branch (address above) and may be seen by interested persons 
between 9 a.m. and 4 p.m., Monday through Friday.

    (1) Memorandum of meeting between Industry and FDA Personnel, 
December 2, 1983, coded MM0002, Docket No. 81N-0022, Dockets 
Management Branch.
    (2) Memorandum of meeting between Industry and FDA Personnel, 
April 11, 1984, coded MM0003, Docket No. 81N-0022, Dockets 
Management Branch.
    (3) Comment No. LET86, Docket No. 81N-0022, Dockets Management 
Branch.
    (4) Blackburn, G.L. et al., ``Determinants of the Pressor Effect 
of Phenylpropanolamine in Healthy Subjects,'' Journal of the 
American Medical Association, 261:3267-3271, 1989, in Comment No. 
C94, Vol. 6, Docket No. 81N-0022, Dockets Management Branch.
    (5) Comment No. MM11, Docket No. 81N-0022, Dockets Management 
Branch.
    (6) Comment No. C107, Docket No. 81N-0022, Dockets Management 
Branch.

III. The Agency Proposal

    The agency is proposing to amend part 201 (21 CFR part 201) by 
adding new Sec. 201.321 entitled: ``Over-the-counter drugs containing 
phenylpropanolamine as an active ingredient; required warnings.'' This 
section would require new warnings for all OTC drug products containing 
phenylpropanolamine. The agency has made an effort to shorten and 
simplify the labeling by combining the warnings and drug interaction 
precautions under 

[[Page 5914]]
four new headings in the ``Warnings'' section. Manufacturers can use 
bullets or other identifying marks to emphasize the warnings. The 
format of the ``Warnings'' section of the product's labeling might look 
something like the following:

    DO NOT TAKE MORE THAN (these words in bold print and capital 
letters) 75 milligrams per day (24 hours). Taking more can be 
harmful. DO NOT TAKE IF (these words in bold print and capital 
letters) you have

 Heart or thyroid disease
 High blood pressure
 An enlarged prostrate gland
Unless directed by a doctor.

    STOP USING IF (these words in bold print and capital letters) 
you develop

 Nervousness
 Dizziness
     Sleeplessness
     Headache
     Palpitations.
    If symptoms continue, ask a doctor. DO NOT USE WITH (these words 
in bold print and capital letters)
     A monoamine oxidase inhibitor (MAOI) (certain drugs for 
depression, psychiatric or emotional conditions, or Parkinson's 
disease), or for 2 weeks after stopping the MAOI drug. If unsure, 
ask a health professional.
     Any allergy, asthma, cough-cold, nasal decongestant, or 
weight control product (containing phenylpropanolamine, 
phenylephrine, pseudoephedrine, or ephedrine), or any prescription 
drug, unless directed by a doctor.

    The agency is proposing this format as an example of how this 
warning information might be presented in a clearer and more readable 
way. The agency is currently considering a new standardized format for 
the labeling of all OTC drug products. (See the Federal Register of 
August 16, 1995, 60 FR 42578). Thus, the format proposed in this 
document may change in the future as a format is developed to label all 
classes of OTC drug products. At this time, the agency is primarily 
seeking specific comment on the wording of the proposed warnings for 
phenylpropanolamine. Comments on the labeling format will also be 
considered. As discussed below, the agency is encouraging manufacturers 
to implement this proposed labeling for their phenylpropanolamine drug 
products as soon as possible. The agency's proposed labeling format or 
any similar format would be acceptable to use at this time.
    The agency is aware that the labeling proposed by the OTC drug 
industry is currently being used by some manufacturers of OTC 
phenylpropanolamine weight control drug products. FDA encourages 
manufacturers of all OTC drug products containing phenylpropanolamine 
to implement the agency's proposed labeling statements voluntarily as 
soon as possible, subject to the possibility that FDA may change the 
wording of the statements, or not require the statements, as a result 
of comments filed in response to this proposal. Because FDA is 
encouraging that the proposed labeling statements be used on a 
voluntary basis at this time, the agency advises that manufacturers 
will be given ample time after publication of a final rule based on 
this proposal to use up any labeling implemented in conformance with 
this proposal. The agency considers these warnings to be important to 
the safe use of OTC drug products containing phenylpropanolamine. 
Therefore, the agency proposes that this new labeling become effective 
6 months after the date of publication of the final rule in the Federal 
Register. The agency proposes to revoke the existing warning statements 
in Sec. 369.20 (21 CFR 369.20) for ``NASAL PREPARATIONS: 
VASOCONSTRICTORS,'' and ``PHENYLPROPANOLAMINE HYDROCHLORIDE 
PREPARATIONS, ORAL'' at the time that any final rule based on this 
proposal becomes effective.

IV. Analysis of Impacts

    FDA has examined the impacts of the proposed rule under Executive 
Order 12866 and the Regulatory Flexibility Act (Pub. L. 96-354). 
Executive Order 12866 directs agencies to assess all costs and benefits 
of available regulatory alternatives and, when regulation is necessary, 
to select regulatory approaches that maximize net benefits (including 
potential economic, environmental, public health and safety, and other 
advantages; distributive impacts; and equity). The agency believes that 
this proposed rule is consistent with the regulatory philosophy and 
principles identified in the Executive Order. In addition, the proposed 
rule is not a significant regulatory action as defined by the Executive 
Order and, thus, is not subject to review under the Executive Order.
    The Regulatory Flexibility Act requires agencies to analyze 
regulatory options that would minimize any significant impact of a rule 
on small entities. This proposed rule will require some relabeling for 
products containing phenylpropanolamine. This relabeling will impose 
direct one-time costs that are expected to be minimal. Accordingly, the 
agency certifies that the proposed rule will not have a significant 
economic impact on a substantial number of small entities. Therefore, 
under the Regulatory Flexibility Act, no further analysis is required.
    The agency invites public comment regarding any substantial or 
significant economic impact that this rulemaking would have on 
manufacturers of drug products containing phenylpropanolamine. Comments 
regarding the impact of this rulemaking on OTC phenylpropanolamine drug 
products should be accompanied by appropriate documentation. A period 
of 90 days from the date of publication of this proposed rulemaking in 
the Federal Register will be provided for comments on this subject to 
be developed and submitted. The agency will evaluate any comments and 
supporting data that are received and will reassess the economic impact 
of this rulemaking in the preamble to the final rule.

Paperwork Reduction Act of 1995

    FDA tentatively concludes that the labeling requirements proposed 
in this document are not subject to review by the Office of Management 
and Budget because they do not constitute a ``collection of 
information'' under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501 
et seq.). Rather, the proposed warning statements are a ``public 
disclosure of information originally supplied by the Federal government 
to the recipient for the purpose of disclosure to the public'' (5 CFR 
1320.3(c)(2)).

VI. Environmental Impact

    The agency has determined under 21 CFR 25.24(c)(6) that this action 
is of a type that does not individually or cumulatively have a 
significant effect on the human environment. Therefore, neither an 
environmental assessment not an environmental impact statement is 
required.

VII. Request for Comments

    Interested persons may, on or before May 14, 1996, submit written 
comments on the proposed regulation to the Dockets Management Branch 
(address above). Written comments on the agency's economic impact 
determination may be submitted on or before May 14, 1996. Three copies 
of all comments are to be submitted, except that individuals may submit 
one copy. Comments are to be identified with the docket number found in 
brackets in the heading of this document and may be accompanied by a 
supporting memorandum or brief. Received comments may be seen in the 
office above between 9 a.m. and 4 p.m., Monday through Friday. 

[[Page 5915]]


List of Subjects

21 CFR Part 201

    Drugs, Labeling, Reporting and recordkeeping requirements.

21 CFR Part 369

    Labeling, Medical devices, Over-the-counter drugs.

    Therefore, under the Federal Food, Drug, and Cosmetic Act, and 
under authority delegated to the Commissioner of Food and Drugs, it is 
proposed that 21 CFR parts 201 and 369 be amended as follows:

PART 201--LABELING

    1. The authority citation for 21 CFR Part 201 continues to read as 
follows:

    Authority: Secs. 201, 301, 501, 502, 503, 505, 506, 507, 508, 
510, 512, 530-542, 701, 704, 721 of the Federal Food, Drug, and 
Cosmetic Act (21 U.S.C. 321, 331, 351, 352, 353, 355, 356, 357, 358, 
360, 360b, 360gg-360ss, 371, 374, 379e); secs. 215, 301, 351, 361 of 
the Public Health Service Act (42 U.S.C. 216, 241, 262, 264).

    2. New Sec. 201.321 is added to subpart G to read as follows:


Sec. 201.321  Over-the-counter drugs containing phenylpropanolamine as 
an active ingredient; required labeling.

    (a) Phenylpropanolamine is a sympathomimetic drug used in both 
over-the-counter (OTC) weight control and nasal decongestant (cough-
cold) drug products. The Food and Drug Administration is concerned that 
adverse reactions could occur if a consumer inadvertently ingests 
excessive amounts of phenylpropanolamine by taking a weight control and 
a cough-cold drug product containing phenylpropanolamine concurrently, 
or by taking products containing phenylpropanolamine and another 
sympathomimetic drug (nasal decongestant or bronchodilator) 
concurrently. In addition, because phenylpropanolamine is a 
sympathomimetic ingredient that interacts with monoamine oxidase 
inhibitor drugs and can cause serious adverse effects, the two types of 
drugs should not be taken concurrently. Further, phenylpropanolamine 
should not be used by persons with high blood pressure, heart or 
thyroid disease, or diabetes.
    (b) Any allergy, cough-cold, or nasal decongestant drug product 
containing phenylpropanolamine bitartrate, phenylpropanolamine 
hydrochloride, or phenylpropanolamine maleate as an active ingredient 
in an oral dosage form for OTC use as described in paragraph (a) of 
this section is misbranded within the meaning of section 502 of the 
Federal Food, Drug, and Cosmetic Act (the act) unless its labeling 
bears the following statements under the heading ``WARNINGS:''
    (1) For oral nasal decongestants labeled for adults only or for 
both adults and children under 12 years of age.
    (i) ``DO NOT TAKE MORE THAN'' (these five words in bold print and 
capital letters) (insert maximum 150 mg daily adult dose in a 24-hour 
period or maximum children's doses broken down by age groups, expressed 
in units such as capsules or teaspoonfuls) ``per day (24 hours). Taking 
more can be harmful.''
    (ii) ``DO NOT TAKE IF'' (these four words in bold print and capital 
letters) ``you have heart or thyroid disease, high blood pressure, or 
an enlarged prostate gland, unless directed by a doctor.'' (Information 
may be indented and/or preceded by a bullet or other identifying mark.)
    (iii) ``STOP USING IF'' (these three words in bold print and 
capital letters) ``you develop nervousness, dizziness, sleeplessness, 
headache, or palpitations. If symptoms continue, ask a doctor.'' 
(Information may be indented and/or preceded by a bullet or other 
identifying mark.)
    (iv) ``DO NOT USE WITH'' (these four words in bold print and 
capital letters) (a) ``a monoamine oxidase inhibitor (MAOI) (certain 
drugs for depression, psychiatric or emotional conditions, or 
Parkinson's disease), or for 2 weeks after stopping the MAOI drug. If 
unsure, ask a health professional.'' (b) ``any allergy, asthma, cough-
cold, nasal decongestant, or weight control product (containing 
phenylpropanolamine, phenylephrine, pseudoephedrine, or ephedrine), or 
any prescription drug, unless directed by a doctor.'' (Statements (a) 
and (b) under this heading may be indented and/or preceded by a bullet 
or other identifying mark.)
    (2) For oral nasal decongestants labeled only for children under 12 
years of age. The same labeling of the product contains the same 
warnings identified in paragraph (b)(i) of this section except that the 
words ``or Parkinson's disease'' under ``DO NOT USE WITH'' may be 
deleted.
    (c) Any weight control drug product containing phenylpropanolamine 
bitartrate, phenylpropanolamine hydrochloride, or phenylpropanolamine 
maleate as an active ingredient in an oral dosage form for OTC use as 
described in paragraph (a) of this section is misbranded within the 
meaning of section 502 of the act unless its labeling bears the 
following statements under the heading ``WARNINGS:''
    (1) ``For use by people 18 years of age and older.''
    (2) ``DO NOT TAKE MORE THAN'' (these five words in bold print and 
capital letters) (insert maximum 75 mg daily dose in a 24-hour period, 
expressed in units such as capsules or tablets) ``per day (24 hours). 
Taking more WILL NOT (these two words in bold print and capital 
letters) increase weight loss and can be harmful.''
    (3) ``DO NOT TAKE IF'' (these four words in bold print and capital 
letters) ``you have heart or thyroid disease, high blood pressure, or 
an enlarged prostate gland, unless directed by a doctor.'' (Information 
may be indented and/or preceded by a bullet or other identifying mark.)
    (4) ``STOP USING IF'' (these three words in bold print and capital 
letters) ``you develop nervousness, dizziness, sleeplessness, headache, 
or palpitations. If symptoms continue, ask a doctor.'' (Information may 
be indented and/or preceded by a bullet or other identifying mark.)
    (5) ``DO NOT USE WITH'' (these four words in bold print and capital 
letters) (a) ``a monoamine oxidase inhibitor (MAOI) (certain drugs for 
depression, psychiatric or emotional conditions, or Parkinson's 
disease), or for 2 weeks after stopping the MAOI drug. If unsure, ask a 
health professional.'' (b) ``any allergy, asthma, cough-cold, nasal 
decongestant, or weight control product (containing 
phenylpropanolamine, phenylephrine, pseudoephedrine, or ephedrine), or 
any prescription drug, unless directed by a doctor.'' (Statements (a) 
and (b) under this heading may be indented and/or preceded by a bullet 
or other identifying mark.)
    (d) After (date 6 months after date of publication of the final 
rule in the Federal Register), any such OTC drug product initially 
introduced or initially delivered for introduction into interstate 
commerce, or any such drug product that is repackaged or relabeled 
after this date regardless of the date the product was manufactured, 
initially introduced, or initially delivered for introduction into 
interstate commerce, that is not in compliance with this section is 
subject to regulatory action.

PART 369--INTERPRETATIVE STATEMENTS RE WARNINGS ON DRUGS AND 
DEVICES FOR OVER-THE-COUNTER SALE

    3. The authority citation for 21 CFR part 369 continues to read as 
follows:

    Authority: Secs. 201, 301, 501, 502, 503, 505, 506, 507, 701 of 
the Federal Food, Drug, 

[[Page 5916]]
and Cosmetic Act (21 U.S.C. 321, 331, 351, 352, 353, 355, 356, 357, 
371).


Sec. 369.20  [Amended]

    4. Section 369.20 Drugs; recommended warning and caution statements 
is amended by removing the entries for ``NASAL PREPARATIONS: 
VASOCONSTRICTORS,'' and ``PHENYLPROPANOLAMINE HYDROCHLORIDE 
PREPARATIONS, ORAL.''

    Dated: February 6, 1996.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 96-3323 Filed 2-13-96; 8:45 am]
BILLING CODE 4160-01-P