[Federal Register: December 6, 2002 (Volume 67, Number 235)]
[Rules and Regulations]
[Page 72555-72559]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr06de02-3]
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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
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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
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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