[Federal Register Volume 67, Number 235 (Friday, December 6, 2002)]
[Rules and Regulations]
[Pages 72555-72559]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-30641]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 336, 338, and 341

[Docket No. 97N-0128]
RIN 0910-AA01


Labeling of Diphenhydramine-Containing Drug Products for Over-
the-Counter Human Use

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is issuing a final rule 
amending the final monographs for over-the-counter (OTC) antiemetic, 
antihistamine, antitussive, and nighttime sleep-aid drug products to 
add a warning statement for oral products containing diphenhydramine 
citrate or diphenhydramine hydrochloride. The warning advises consumers 
not to use oral OTC diphenhydramine products with any other product 
containing diphenhydramine, including products used topically. This 
final rule also includes the agency's conclusions on additional warning 
statements and a direction statement for OTC external analgesic drug 
products containing diphenhydramine hydrochloride. These conclusions 
will be incorporated into the final monograph for OTC external 
analgesic drug products in a future issue of the Federal Register. FDA 
is issuing this final rule after considering public comments on the 
agency's proposed regulation and all new data and information on drug 
products containing diphenhydramine that have come to the agency's 
attention.

DATES: 
    Effective Date: This regulation is effective December 8, 2003.
    Compliance Dates: The compliance date for oral products with annual 
sales less than $25,000 is December 6, 2004. The compliance date for 
all other oral products is December 8, 2003.

FOR FURTHER INFORMATION CONTACT: Michael T. Benson, Center for Drug 
Evaluation and Research (HFD-560), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-2222.

SUPPLEMENTARY INFORMATION:

I. Background

    In the Federal Register of August 29, 1997 (62 FR 45767), FDA 
published a notice of proposed rulemaking to amend the tentative final 
monograph (TFM) for OTC external analgesic drug products (proposed 21 
CFR 348.50(c)(10)) to add the following warning statement for 
diphenhydramine hydrochloride: ``Do Not Use:'' (these three words in 
bold print) ``on chicken pox, poison ivy, sunburn, large areas of the 
body, broken, blistered, or oozing skin, more often than directed, or 
with any other product containing diphenhydramine, even one taken by 
mouth.'' The agency also proposed to amend the final monographs for OTC 
antiemetic (proposed 21 CFR 336.50(c)(8)), antihistamine (proposed 21 
CFR 341.72(c)(6)(iv) and (c)(7)) and antitussive (proposed 21 CFR 
341.74(c)(4)(viii)(C) and (c)(4)(ix)(C)), and nighttime sleep-aid 
(proposed 21 CFR 338.50(c)(5)) drug products to add the following 
warning statement for diphenhydramine ingredients: ``Do Not Use'' 
(these three words in bold print) ``with any other product containing 
diphenhydramine, including one applied topically.'' The agency proposed 
these warnings based on reports of adverse events when oral and topical 
diphenhydramine products were used concurrently. In response to that 
proposal, two manufacturers and a marketing association submitted 
comments. The agency is responding to those comments and publishing a 
final rule that applies to oral diphenhydramine products now and to 
topical diphenhydramine products at a future date.
    Twenty-four months after the date of publication in the Federal 
Register, for oral diphenhydramine-containing products with sales less 
than $25,000, and 12 months after the after the date of publication in 
the Federal Register, for all other such oral products, no OTC drug 
product that is subject to this final rule and that contains a 
nonmonograph condition may be initially introduced or initially 
delivered for introduction into interstate commerce unless it is the 
subject of an approved new drug application or abbreviated new drug 
application. Further, any OTC drug product subject to this final rule 
that is repackaged or relabeled after the compliance dates of the final 
rule must be in compliance with the applicable monograph regardless of 
the date the product was initially introduced or initially delivered 
for introduction into interstate commerce. Manufacturers are encouraged 
to comply voluntarily as soon as possible.

II. The Agency's Conclusion on the Comments

    (Comment 1) One comment contended that the proposed label changes 
for diphenhydramine products are not necessary and would have no 
significant impact. The comment stated that the 23 reported cases of 
toxicity between 1979 and 1989 discussed in the proposal (62 FR 45767 
at 45768) are minute compared to the millions of applications of these 
topical products. Further, in all cases, the toxicity was due to 
consumer noncompliance with directions and indications. In the majority 
of cases, no treatment was required except for discontinuance of the 
drug, with affected consumers released from medical care in 24 hours. 
The comment concluded that additional warnings would have no effect on 
consumers who have obviously ignored the existing warnings.
    The agency disagrees. The agency recognizes that the number of 
reports is small compared to the total doses used. However, there is 
particular concern because of the reports of toxic psychosis, 
especially in children, discussed in the proposed rule. There is also 
concern of underreporting because there is no current reporting

[[Page 72556]]

requirement for topical diphenhydramine products marketed under the 
proposed OTC drug monograph. As pointed out in the proposal (62 FR 
45767 at 45769), a major manufacturer voluntarily revised the warnings 
for its topical diphenhydramine products after receiving adverse 
reaction reports. The agency concludes that additional labeling 
information should help reduce possible misuse of these products and 
reduce the possibility of serious adverse reactions.
    As noted, our decision to require the warning set forth in this 
final rule is based on other comments made in response to the proposed 
rule and our analysis of numerous adverse event reports that document 
the potential health risks associated with the concurrent use of OTC 
drug products that contain diphenhydramine. Mandating a warning does 
not require a finding that any or all of the OTC drug products that 
contain diphenhydramine actually caused an adverse event, and FDA does 
not so find. Nor does FDA's mandate of a warning repudiate the OTC drug 
monographs under which the affected drug products have been lawfully 
marketed. Rather, as a consumer protection agency, FDA has determined 
that this additional warning is necessary to ensure that these OTC drug 
products continue to be safe and effective for their labeled 
indications under ordinary conditions of use as those terms are defined 
in the Federal Food, Drug, and Cosmetic Act. This judgment balances the 
benefits of these drug products against their potential risks, and 
reflects our conclusion that even a potential link between the overuse 
of diphenhydramine and serious adverse health consequences warrants 
this action (see 21 CFR 330.10(a)).
    FDA's decision to act in an instance such as this one need not meet 
the standard of proof required to prevail in a private tort action 
(Glastetter v. Novartis Pharmaceuticals, Corp., 252 F. 3d 986, 991 (8th 
Cir. 2001)). To mandate a warning, or take similar regulatory action, 
FDA need not show, nor do we allege, actual causation.
    The distinction between avoidance of risk through regulation and 
compensation for injuries after the fact is a fundamental one. In 
the former, risk assessments may lead to control of a toxic 
substance even though the probability of harm to any individual is 
small and the studies necessary to assess the risk are incomplete; 
society as a whole is willing to pay the price as a matter of 
policy. In the latter, a far higher probability (greater than 50%) 
is required since the law believes it is unfair to require an 
individual to pay for another's tragedy unless it is shown that it 
is more likely than not that he caused it * * * .
In re ``Agent Orange'' Product Liability Litigation, 597 F. Supp. 740, 
781 (E.D.N.Y. 1984), aff'd., 818 F. 2d 145 (2d Cir. 1987) at 781. In 
making its decision, the agency follows ``the preventive perspective 
that [ ] agencies adopt in order to reduce public exposure to harmful 
substances.'' Glastetter, 252 F.3d at 991, quoting Hollander v. Sandoz 
Pharmaceuticals, Corp., 95 F. Supp.2d 1230, 1234 n. 9 (W.D. Okla. 
2000). This is what we have done here.
    (Comment 2) Two comments contended that OTC topical diphenhydramine 
products indicated for ``pain and itch of sunburn and poison ivy'' 
should not be contraindicated for the same uses and that the agency's 
proposed warning could confuse consumers. The comments added that the 
proposed labeling could be interpreted to mean that usage on large 
areas of the body is permitted as long as the product is not used more 
than three to four times daily. One comment stated that the proposal 
only cited two reports of toxicity when the drug was applied topically 
to a widespread area of intact sunburned skin and to a severe case of 
poison ivy. There were no reported cases when the drug was applied on 
limited areas of skin compromised with poison ivy or sunburn. The 
comment recommended that the labeling state ``do not use more often 
than directed,'' and that this part of the warning be moved to 
``Directions'' because the statement relates to dosing.
    Another comment agreed that topical diphenhydramine products should 
not be used on large areas of skin either intact or with open lesions. 
However, it objected to warning against use on damaged skin conditions, 
specifically broken, blistered, or oozing skin, contending that such 
labeling may confuse consumers seeking use for skin conditions such as 
minor cuts, minor burns, or insect bites that are characterized by 
broken, blistered, or oozing skin. Further, the comment was unable to 
find any adverse event cases reported when the product was applied 
according to the labeled directions on limited areas of damaged skin. A 
second comment also was unable to find any adverse reports associated 
with use on limited areas of damaged skin. It noted the cited cases in 
the proposal concerned application on compromised skin over a large 
skin surface. The comment suggested that this problem is best addressed 
by the warning against use ``on large areas of the body.''
    The agency agrees that topical diphenhydramine products should be 
indicated for use on limited areas of skin with poison ivy or sunburn 
and that the warning is intended to alert consumers not to use these 
products over large areas of the body or more often than directed for 
any condition. Because sunburn, poison ivy, and other conditions for 
which topical diphenhydramine is used (e.g., minor cuts and burns, and 
insect bites) could be characterized by ``broken, blistered, or oozing 
skin,'' the agency is removing these conditions from the proposed 
warning.
    Since the proposal was published, the agency has established a new 
labeling format for all OTC drug products (see section III in this 
document). That labeling format conveys information in a segmented 
manner. Based on the new labeling format and the revisions described in 
the previous paragraph, the information in the final warning for 
topical products would now appear as follows: ``Do not use [bullet] on 
large areas of the body [bullet] with any other product containing 
diphenhydramine, even one taken by mouth,'' ``Ask a doctor before use 
[bullet] on chicken pox [bullet] on measles,'' and under ``Directions 
[bullet] do not use more often than directed.'' The proposed monograph 
directions for external analgesic drug products containing 
diphenhydramine are ``Apply to affected area not more than 3 to 4 times 
daily.'' The agency concludes that the revised warnings and directions 
should be clearer and more understandable to consumers.
    (Comment 3) One comment recommended changing ``Do not use on 
chicken pox'' to ``Do not use on chicken pox, except as directed by a 
physician.'' The comment cited additional toxicity reports not included 
in the proposed rule in which diphenhydramine was applied liberally on 
children with large areas of chicken pox. However, the comment stated 
that since physicians may find use appropriate in select cases, 
consumers should be advised to consult their physicians. Another 
comment agreed because a doctor may advise use on a few itchy spots to 
help prevent scratching and the scarring that could result.
    One comment from a manufacturer proposed that ``measles'' be 
included because a case of diphenhydramine toxicity after treatment 
with diphenhydramine for measles had been reported to the company. The 
comment noted that the adverse event was similar to the chicken pox 
cases discussed in the proposed rule, and that both chicken pox and 
measles may appear as a widespread rash. Another comment concurred and 
proposed the following:

[[Page 72557]]

 ``Ask a doctor before use on chicken pox or measles.''
    The agency agrees. In the proposal, the agency stated that because 
none of the case reports was associated with measles, that condition 
was not specifically listed in the warning (62 FR 45767 at 45771). The 
agency invited comments related to any adverse events associated with 
the topical application of diphenhydramine to measles. As there has 
been at least one measles case report and since chicken pox and measles 
may appear similar to consumers, the agency is including both 
conditions in product labeling. The agency did not receive any comments 
opposed to including measles in labeling. When the monograph for OTC 
external analgesic drug products becomes final, it will contain the 
following warning for topical diphenhydramine products: ``Ask a doctor 
before use [bullet] on chicken pox [bullet] on measles.''
    (Comment 4) Two comments agreed that it was reasonable to add a 
warning to the labeling of OTC oral diphenhydramine products. The 
comments recommended revising the last part of the agency's proposed 
warning from ``including one applied topically'' to ``even one used on 
skin'' for two reasons. First, the revised language comprises six 
syllables in five words instead of nine syllables in four words, making 
it easier to read. Second, consumers who do not understand the meaning 
of the word ``topically'' are more likely to know what is meant by ``on 
skin.''
    The agency agrees and has revised the labeling for OTC 
diphenhydramine oral products to read: ``Do not use: [bullet] with any 
other product containing diphenhydramine, even one used on skin.''
    (Comment 5) One comment expressed concern over the cost of 
implementing the new labeling for a small manufacturer of topical 
products and contended: (1) The proposed labeling is an example of the 
type of regulation that Executive Order 12866 and the Regulatory 
Flexibility Act were intended to eliminate; (2) the cost to relabel 
would be substantially more than the $2,000 to $3,000 the agency 
mentioned in the proposal because of ordering requirements for tubes 
and boxes and a low dollar volume of annual sales; (3) existing 
inventory would have to be destroyed because it would not be used prior 
to the effective date for new labeling; and (4) there would be 
excessive costs associated with producing new graphics for labeling all 
products. The comment did not provide any specific data or figures to 
support its cost speculation.
    The agency disagrees that the proposed labeling is an example of 
the type of regulation that Executive Order 12866 and the Regulatory 
Flexibility Act were intended to eliminate. The agency has determined 
that the additional warning statement is necessary for the safe and 
effective use of OTC drug products that contain diphenhydramine. The 
proposed rule (62 FR 45767 at 45772 to 45773) and this final rule 
(section V of this document) examine the impacts of the rule under 
Executive Order 12866 and the Regulatory Flexibility Act.
    The $2,000 to $3,000 relabeling cost stated by the agency in the 
proposal (62 FR 45767 at 45772) was based on information that the 
agency obtained from various drug manufacturers, both small and large. 
That relabeling cost included the cost associated with producing new 
graphics for labeling products and the cost of tubes and boxes on which 
the labeling would be printed.
    The agency does not anticipate that significant existing inventory 
would have to be destroyed because it would not be used prior to the 
effective date for new labeling. It has been almost 5 years since the 
proposed rule was published, and existing inventory should have been 
reduced during this time. In addition, manufacturers still have 
adequate time to deplete existing stocks of inventory. This final rule 
has a compliance date of 24 months after its publication in the Federal 
Register for oral products containing diphenhydramine citrate or 
diphenhydramine hydrochloride with annual sales less than $25,000, and 
a compliance date of 12 months after its publication in the Federal 
Register for all other oral products. The monograph for topical 
(external analgesic) drug products containing diphenhydramine [products 
in tubes] is not yet final and, when issued, will specify the time by 
which relabeling is required. Manufacturers of topically applied 
diphenhydramine products are encouraged to implement the new labeling 
at an earlier date should they need to order additional labeling for 
their products before the agency issues the final monograph for OTC 
external analgesic drug products.
    Since the proposal was published in 1997, the agency issued a final 
rule on March 17, 1999 (64 FR 13254) establishing a new standardized 
labeling format and content for all OTC drug products (the 1999 final 
rule). That final rule contained an extensive discussion of the costs 
of relabeling OTC drug products, including the impact on small 
businesses (64 FR 13254 at 13284 to 13285). In an effort to reduce the 
economic impact on small businesses, the agency generally provides an 
additional 12 months of compliance time for relabeling of OTC drug 
products with annual sales less than $25,000 which is being provided 
for oral diphenhydramine drug products in this final rule.

III. New Labeling Format

    In the 1999 final rule, the agency established standardized format 
and standardized content requirements for the labeling of OTC drug 
products set forth in Sec.  201.66 (21 CFR 201.66). The requirements 
relate to the labeling for diphenhydramine-containing OTC drug products 
by including bullets prior to certain words under the ``Warnings'' 
subheadings ``Do not use'' and ``Ask a doctor before use'' and prior to 
the direction ``do not use more often than directed.'' The subheadings 
are highlighted in bold type in accordance with Sec.  201.66(c)(5). 
Pertinent parts of the new labeling are in tables 1 and 2 of this 
document.

 Table 1.--Warning for Oral Antiemetic, Antihistamine, Antitussive, and
Nighttime Sleep-Aid Drug Products Containing Diphenhydramine Ingredients
------------------------------------------------------------------------
                Warnings
----------------------------------------
Do not use
[sbull] with any other product containing diphenhydramine, even one used
 on skin
------------------------------------------------------------------------


  Table 2.--Warnings and Direction for External Analgesic Drug Products
                 Containing Diphenhydramine Ingredients
------------------------------------------------------------------------
                Warnings
----------------------------------------
[sbull] For external use only
----------------------------------------
Do not use
[sbull] on large areas of the body
[sbull] with any other product containing diphenhydramine, even one
 taken by mouth
----------------------------------------
Ask a doctor before use
[sbull] on chicken pox [sbull] on measles
----------------------------------------
Directions
[sbull] do not use more often than
 directed
------------------------------------------------------------------------

IV. The Agency's Final Conclusions

    Based on the available evidence, the agency is issuing a final rule 
amending the final monographs for orally administered OTC antiemetic,

[[Page 72558]]

antihistamine, antitussive, and nighttime sleep-aid drug products 
containing diphenhydramine to include the new warning in table 1 of 
this document. This final rule also discusses new warnings and a 
direction in table 2 of this document that will be incorporated into 
the final monograph for OTC external analgesic drug products in a 
future issue of the Federal Register, when the complete monograph for 
those products is published.

V. Analysis of Impacts

    FDA has examined the impacts of the final rule under Executive 
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612), and 
the Unfunded Mandates Reform Act of 1995 (Public Law 104-4). 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). Under the Regulatory 
Flexibility Act, if a rule has a significant economic impact on a 
substantial number of small entities, an agency must analyze regulatory 
options that would minimize any significant impact of the rule on small 
entities. Section 202(a) of the Unfunded Mandates Reform Act requires 
that agencies prepare a written statement and economic analysis before 
proposing any rule that may result in an expenditure in any one year by 
State, local, and tribal governments, in the aggregate, or by the 
private sector, of $100 million (adjusted annually for inflation).
    The agency concludes that this final rule is consistent with the 
principles set out in the Executive order and in these two statutes. 
The final rule is not a significant regulatory action as defined by the 
Executive order and so is not subject to review under the Executive 
order. As discussed in this section, FDA has determined that this final 
rule will not have a significant economic impact on a substantial 
number of small entities. The Unfunded Mandates Reform Act does not 
require FDA to prepare a statement of costs and benefits for this final 
rule because the final rule is not expected to result in any 1-year 
expenditure that would exceed $100 million adjusted for inflation. The 
current inflation adjusted statutory threshold is about $110 million.
    The purpose of this final rule is to add the same warning statement 
for four categories of OTC drugs in three different OTC drug monographs 
that include products containing diphenhydramine taken orally. Based on 
information in the agency's drug listing system (DLS), there are 
approximately 95 manufacturers, 59 repackers, and 247 distributors of 
about 800 to 1,000 oral diphenhydramine products. The agency does not 
believe these companies would need to increase the package size to add 
this warning and, thus, they should incur only minor costs to relabel 
their products. The agency believes that relabeling costs of the type 
required by this final rule generally average about $2,000 to $3,000 
per stock keeping unit (SKU) (individual products, packages, and 
sizes). Assuming that there are about 800 to 1,000 affected SKUs in the 
marketplace, total one-time costs of relabeling would be $1.6 million 
($2,000 per SKU x 800 SKUs) to $3 million ($3,000 per SKU x 1,000 
SKUs). The agency believes the actual cost would be lower because most 
of the labeling changes will be made by private label manufacturers 
that tend to use simpler and less expensive labeling.
    Manufacturers of oral diphenhydramine-containing products will 
incur most of the costs associated with this final rule. The impact on 
any one firm will vary based on the number and types of products that 
need relabeling. About 85 percent of the manufacturers meet the Small 
Business Administration's definition of a small entity (fewer than 750 
employees). In the proposal (62 FR 45767 at 45772 to 45773), the agency 
estimated that the proposed rule may have a significant impact on some 
small entities. On further analysis, the agency now believes that the 
final rule will not have a significant impact on a substantial number 
of small entities because about one-half of the firms have listed only 
one diphenhydramine-containing product with the agency, another 30 
percent have listed two or three products, and all of the manufacturers 
produce a number of other OTC drug products not affected by this rule. 
The agency does not believe the cost to any one firm to relabel its 
products subject to this final rule will approach 1 percent of the 
entity's income.
    The DLS also identifies approximately 30 manufacturers, 4 
repackers, and 53 distributors of about 100 topical diphenhydramine 
products. The cost for these companies to relabel their products will 
be discussed in the final monograph for OTC external analgesic drug 
products.
    The agency considered but rejected several alternatives: (1) A 
shorter or longer implementation period, and (2) an exemption from 
coverage for small entities. While the agency believes that consumers 
would benefit from having this new labeling in place as soon as 
possible, the agency also acknowledges that a shorter implementation 
period could significantly increase the compliance costs and these 
costs could be passed through to consumers. A longer time period would 
unnecessarily delay the benefit of new labeling to consumers who self-
medicate with these OTC antiemetic, antihistamine, antitussive, and 
nighttime sleep-aid drug products. The agency rejected an exemption for 
small entities because the new labeling is also needed by consumers who 
purchase products marketed by those entities. However, a longer 
compliance date until 24 months after date of publication in the 
Federal Register is being provided for products with annual sales less 
than $25,000.
    For the reasons in this section and under the Regulatory 
Flexibility Act (5 U.S.C. 605(b)), the agency certifies that this final 
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.

VI. Paperwork Reduction Act of 1995

    FDA concludes that the labeling requirements 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 
labeling 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)).

VII. Environmental Impact

    The agency has determined under 21 CFR 25.31(a) 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 nor an environmental impact statement is required.

VIII. Federalism

    FDA has analyzed this final rule in accordance with the principles 
set forth in Executive Order 13132. FDA has determined that the rule 
does not contain policies that have substantial direct effects on the 
States, on the relationship between the National Government and the 
States, or on the distribution of power and responsibilities among the 
various levels of government. Accordingly, the agency has concluded 
that the rule does

[[Page 72559]]

not contain policies that have federalism implications as defined in 
the Executive order and, consequently, a federalism summary impact 
statement is not required.

List of Subjects in 21 CFR Parts 336, 338, and 341

    Labeling, Over-the-counter drugs.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR parts 
336, 338, and 341 are amended as follows:

PART 336--ANTIEMETIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE

    1. The authority citation for 21 CFR part 336 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.
    2. Section 336.50 is amended by adding paragraph (c)(8) to read as 
follows:


Sec.  336.50  Labeling of antiemetic drug products.

* * * * *
    (c) * * *
    (8) For products containing diphenhydramine hydrochloride 
identified in Sec.  336.10(c). ``Do not use [bullet]\1\ with any other 
product containing diphenhydramine, including one used on skin''.
---------------------------------------------------------------------------

    \1\ See Sec.  201.66(b)(4) of this chapter for definition of 
bullet symbol.
---------------------------------------------------------------------------

* * * * *

PART 338--NIGHTTIME SLEEP-AID DRUG PRODUCTS FOR OVER-THE-COUNTER 
HUMAN USE

    3. The authority citation for 21 CFR part 338 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.
    4. Section 338.50 is amended by adding paragraph (c)(5) to read as 
follows:


Sec.  338.50  Labeling of nighttime sleep-aid drug products.

* * * * *
    (c) * * *
    (5) ``Do not use [bullet]\1\ with any other product containing 
diphenhydramine, even one used on skin''.
---------------------------------------------------------------------------

    \1\ See Sec.  201.66(b)(4) of this chapter for definition of 
bullet symbol.
---------------------------------------------------------------------------

* * * * *

PART 341--COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC 
DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE

    5. The authority citation for 21 CFR part 341 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.
    6. Section 341.72 is amended by adding paragraphs (c)(6)(iv) and 
(c)(7) as follows:


Sec.  341.72  Labeling of antihistamine drug products.

* * * * *
    (c) * * *
    (6) * * *
    (iv) For products containing diphenhydramine citrate or 
diphenhydramine hydrochloride identified in Sec.  341.12(f) and (g). 
``Do not use [bullet]\1\ with any other product containing 
diphenhydramine, even one used on skin''.
---------------------------------------------------------------------------

    \1\ See Sec.  201.66(b)(4) of this chapter for definition of 
bullet symbol.
---------------------------------------------------------------------------

    (7) For products containing diphenhydramine citrate or 
diphenhydramine hydrochloride identified in Sec.  341.12(f) and (g). 
``Do not use [bullet] with any other product containing 
diphenhydramine, even one used on skin''.
* * * * *
    7. Section 341.74 is amended by adding paragraphs (c)(4)(viii)(C) 
and (c)(4)(ix)(C) to read as follows:


Sec.  341.74  Labeling of antitussive drug products.

* * * * *
    (c) * * *
    (4) * * *
    (viii) * * *
    (C) ``Do not use [bullet]\1\ with any other product containing 
diphenhydramine, even one used on skin''.
---------------------------------------------------------------------------

    \1\ See Sec.  201.66(b)(4) of this chapter for definition of 
bullet symbol.
---------------------------------------------------------------------------

* * * * *
    (ix) * * *
    (C) ``Do not use [bullet] with any other product containing 
diphenhydramine, even one used on skin''.
* * * * *

    Dated: November 25, 2002.
Margaret M. Dotzel,
Assistant Commissioner for Policy.
[FR Doc. 02-30641 Filed 12-5-02; 8:45 am]
BILLING CODE 4160-01-S