[Federal Register Volume 61, Number 78 (Monday, April 22, 1996)]
[Rules and Regulations]
[Pages 17798-17806]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-9735]




[[Page 17797]]


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Part IV





Department of Health and Human Services





_______________________________________________________________________



Food and Drug Administration



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21 CFR Parts 201 and 331



Sodium Labeling for Over-the-Counter Drugs and Labeling of Orally 
Ingested Over-the-Counter Drug Products Containing Calcium, Magnesium, 
and Potassium; Final and Proposed Rules

  Federal Register / Vol. 61, No. 78 / Monday, April 22, 1995 / Rules 
and Regulations  

[[Page 17798]]



DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 201 and 331

[Docket No. 90N-0309]
RIN 0910-AA63


Drug Labeling; Sodium Labeling for Over-the-Counter Drugs

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule with opportunity for comments.

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

SUMMARY: The Food and Drug Administration (FDA) is amending the general 
labeling provisions for over-the-counter (OTC) drug products to require 
that the sodium content of all OTC drug products intended for oral 
ingestion be included in labeling when the product contains 5 
milligrams (mg) or more sodium per a single dose; require that all OTC 
drug products intended for oral ingestion containing more than 140 mg 
sodium in the labeled maximum daily dose bear a general warning that 
persons who are on a sodium-restricted diet should not take the product 
unless directed by a doctor; and provide for the voluntary use of 
certain terms (``sodium free,'' ``very low sodium,'' and ``low 
sodium'') relating to an OTC drug product's sodium content per labeled 
maximum daily dose. FDA is issuing this final rule in order to provide 
uniform sodium content labeling for all OTC drug products intended for 
oral ingestion (whether marketed under an OTC drug monograph, an 
approved application, or no application), and to provide for the 
voluntary use in OTC drug labeling of the same terms used to describe 
sodium content in food labeling.

DATES: This final rule is effective April 22, 1997; written comments by 
July 22, 1996.

ADDRESSES: Written comments to the Dockets Management Branch (HFA-305), 
Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23, 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 April 25, 1991 (56 FR 19222), FDA 
proposed to amend the general labeling provisions for OTC drug products 
to: (1) Require that the sodium content of all orally administered OTC 
drug products be included in labeling when the product contains 5 mg or 
more sodium per a single recommended dose; (2) require that orally 
administered OTC drug products containing more than 140 mg sodium in 
the maximum recommended daily dose be labeled with a general warning 
that persons who are on a sodium-restricted diet should not take the 
product unless directed by a doctor; and (3) provide for the voluntary 
use of certain descriptive terms relating to the OTC drug product's 
sodium content. FDA issued the notice of proposed rulemaking in order 
to provide uniform sodium content labeling for all orally administered 
OTC drug products, and to provide for the voluntary use in OTC drug 
labeling of the same descriptive terms as those used to describe sodium 
content in food labeling. To promote uniformity, the agency also 
proposed to delete the existing sodium labeling requirements in the 
final monograph for OTC antacid drug products (21 CFR part 331).
    -Interested persons were invited to file written comments, 
objections, or requests for oral hearing on the proposed regulation 
before the Commissioner of Food and Drugs (the Commissioner) and to 
file comments on the agency's economic impact determination by June 24, 
1991. In the Federal Register of June 12, 1991 (56 FR 26946), FDA 
published a notice extending the comment period until July 24, 1991.
    -In response to the proposed rule, comments were received from five 
state governments, five manufacturers, two trade associations, one 
health professional association, one consumer organization, and FDA 
employees. No comments were received on the agency's economic impact 
determination.-
    -Based on comments received, the agency is seeking comments from 
interested individuals on whether this final rule should be amended to 
include sodium content labeling for OTC rectal laxative, vaginal, 
dentifrice, mouthwash, and mouth rinse drug products. (See section 
I.B., comment 6 of this document.) Comments should be sent to the 
Dockets Management Branch (address above) by July 22, 1996.

II. The Agency's Conclusions on the Comments

A. General Comments

    -1. Most comments generally supported the proposal to include 
sodium content in OTC drug product labeling. A number of the comments 
stated that this labeling would be especially helpful to those 
individuals who must restrict their sodium intake, specifically the 
elderly. Several comments were opposed to the warning statement (see 
section II.D., comment 12 of this document).
    -2. Several comments supported uniform sodium labeling for foods 
and OTC drug products. One comment favored use of the descriptive terms 
``sodium free,'' ``very low sodium,'' and ``low sodium'' for OTC drug 
products because food labeling has made these terms familiar to 
consumers on a low-sodium diet. However, the comment strongly opposed 
sodium warning labeling for OTC drug products, which it considered 
unnecessary and counterproductive (see also section II.D., comment 12 
of this document). Another comment noted that the proposed sodium 
warning requirement for those OTC drugs containing over 140 mg sodium 
per maximum recommended daily dose is consistent with the labeling of 
foods. The comment noted that consumers are familiar with food labeling 
where a serving containing 140 mg or less sodium is considered ``low 
sodium.''
    -Another comment acknowledged the value of the proposed terms, 
provided they are consistent with those used in food labeling. However, 
the comment contended that basing drug labeling on ``per maximum daily 
dosage'' is inconsistent with food labeling which is based on ``per 
serving.'' The comment indicated that ``per dose'' labeling for drugs 
would be more consistent with the food labeling. The comment also noted 
that sodium labeling for foods has no warning threshold, while the 
proposed sodium labeling for OTC drug products does have a warning 
threshold. Another comment stated that drugs are not produced, 
consumed, or regulated like foods and thus should not be treated like 
foods for warning purposes.
    -FDA does not consider sodium labeling for OTC drug products to be 
either unnecessary or counterproductive. The agency has determined that 
such labeling is important and, wherever possible, should be comparable 
to that used for foods because consumers are already familiar with that 
labeling. While consumption patterns for drugs are not the same as 
those for foods, a substantial portion of daily sodium intake can come 
from OTC drugs, especially those used frequently, such as antacids, 
internal analgesics, and laxatives. Thus, the agency concludes that 
consumers

[[Page 17799]]

should be informed about the sodium content of drugs as well as foods.
    -The agency believes that ``maximum daily dose'' is the most 
appropriate basis for sodium descriptor labeling of OTC drug products, 
even though this basis differs from that for food labeling. Consumers 
may use multiple doses per day of many OTC drug products, and OTC drug 
product labeling informs consumers how much of a drug can be safely 
consumed daily. On the other hand, in many cases only a single serving 
of many different foods containing sodium is likely to be consumed in 1 
day, although there is no upper limit on the number of servings that 
could be consumed. Thus, the consumption patterns vary for foods and 
for drugs. Because of food consumption patterns, nutritional labeling, 
including the descriptive terms used, is based on ``per serving,'' and 
the consumer must determine the total daily intake of each food. By 
contrast, OTC drugs have a safe consumption limit, and sodium labeling 
is more appropriately based on the labeled maximum daily dosage. The 
agency is using the term ``labeled maximum daily dosage'' in place of 
``maximum recommended daily dosage'' to indicate that this dosage 
appears in the product's labeling.
    -Although the use of descriptive terms for sodium in the labeling 
of foods is based on the sodium content ``per serving'' rather than on 
a ``maximum daily intake,'' physicians usually monitor a patient's 
total daily sodium intake, not how much is consumed at each meal. When 
physicians instruct people to maintain a low-sodium diet, the 
physicians and individuals determine what foods to avoid to keep the 
daily sodium intake at an acceptable level. If an antacid is needed, 
total daily sodium intake can be reduced by using a calcium antacid 
rather than a sodium antacid.
    -The agency acknowledges that the basis for the descriptive terms 
for sodium labeling of OTC drug products is not the same as for food 
labeling. Nonetheless, the agency considers the two to be consistent. 
In general, the amount of sodium derived from a given OTC drug in 1 day 
is limited to the amount contained in the labeled maximum daily dosage, 
while that derived from a given food is often the amount of sodium in a 
single daily serving. Therefore, in this final rule for OTC drug 
product labeling the agency is providing for the voluntary use of 
descriptive terms for sodium that are based on the labeled maximum 
daily dose. (See also section II.E., comment 15 of this document.)
    -3. One comment expressed concern that descriptive terms based on 
sodium content using rounded-off numbers could be different from 
descriptive terms based on sodium content using actual numbers. The 
comment stated that potential compliance problems could arise if an FDA 
inspector examined the label of an affected product, multiplied the 
rounded-off, approximated sodium content number by the maximum 
recommended daily dose, and arrived at a number that did not fall 
within the range that correlates to the descriptive term on the label. 
The comment contended that calculations for descriptive terms should be 
done using actual sodium content numbers. The comment suggested that if 
discrepancies between actual and rounded-off numbers occur, reasonable 
documentation showing the method of calculation using the actual sodium 
content numbers should be accepted as sufficient to resolve the matter.
    -Another comment supported the first comment's position on the 
rounding-off rules. The comment mentioned the sodium content labeling 
regulation for food in Sec. 101.9(g)(5) (21 CFR 101.9(g)(5)), which 
states: ``A food with a label declaration of calories, sugars, total 
fat, saturated fat, cholesterol, or sodium shall be deemed to be 
misbranded under section 403(a) of the act if the nutrient content of 
the composite is greater than 20 percent in excess of the value for 
that nutrient declared on the label.'' This regulation, referred to as 
the ``120 percent rule,'' provides an upper limit to the amount that 
sodium content may vary in food, above which a product would be deemed 
misbranded. The comment suggested that such a rule for the upper limit 
of variation for sodium labeling for OTC drugs, without an accompanying 
lower limit, would be reasonable because manufacturers will tend to 
declare as low a sodium content as is reasonable for the product. The 
comment contended that applying the ``120 percent rule'' to sodium 
labeling of OTC drugs would alleviate many of the compliance issues 
associated with providing a sodium content on the label that is 
different from the actual sodium content.
    -The agency has reconsidered the ``rounding-off'' provision and 
concludes that rounding-off could result in potential discrepancies 
between the actual and apparent sodium content, and may lead to 
consumer confusion. For instance, if the actual sodium content of a 
product is 8 mg per dosage unit and the product is to be taken four 
times daily, the labeled maximum daily dose is 32 mg. Because the 
sodium content is less than 35 mg (per labeled maximum daily dose), the 
term ``very low sodium'' could be used. However, if the actual dosage 
unit (8 mg) is rounded-off to 10 mg, the apparent labeled maximum daily 
dose for that product would be 40 mg and the descriptive term would be 
``low sodium.''
    -Food labeling regulations provide for rounding-off the sodium 
content to the nearest 5 or 10 mg sodium per serving. Because most food 
products contain naturally occurring sodium, at least in small amounts, 
some variation in sodium content is expected. On the other hand, most 
OTC drug products are manufactured and the amount of sodium in products 
can be strictly controlled. Thus, the sodium content of OTC drug 
products is expected to be less variable than that of foods. The agency 
concludes that the sodium content of OTC drug products can readily be 
disclosed in mg per dosage unit, without rounding-off. As a result, the 
agency considers the ``120 percent rule'' provided for in Sec. 101.9(g) 
of the food regulations unnecessary for OTC drug products. Therefore, 
the agency is revising proposed Sec. 201.64(b) in this final rule (21 
CFR 201.64(b)) to eliminate the 5 mg and 10 mg rounding-off provision. 
The final rule requires that the sodium content be rounded-off to the 
nearest whole number, whatever the content per dosage unit.

B. Comments on the Scope of Sodium Labeling

    -4. Three comments disagreed with the agency's ``across-the-board'' 
sodium warning requirement for OTC drugs, stating that this method 
ignores the OTC drug review's category-by-category mechanism for 
considering warnings. One comment added that if a warning statement is 
required, the agency should consider the product's pharmacologic class, 
its use patterns, and the currently required labeling of particular 
active ingredients. Another comment contended that sodium warnings 
should only be required where a need has been shown for a particular 
category of OTC drugs.
    -FDA disagrees with the comments, which provided no scientific 
basis for their concerns. Although the agency generally considers OTC 
drug labeling on a category-by-category basis, FDA has required certain 
``across-the-board'' labeling during the course of the OTC drug review, 
such as the pregnancy-nursing warning in Sec. 201.63 (21 CFR 201.63). 
Thus, an ``across the board'' approach is consistent with past agency 
regulatory actions. FDA has determined that a certain level (140 mg) of 
sodium

[[Page 17800]]

may present a potential safety problem, regardless of the source of the 
sodium. Therefore, the agency sees no reason to consider the warning on 
a category-by-category basis, which would result in a lack of 
uniformity in product labeling until the agency's evaluation of each 
drug category is completed. The agency's ``across-the-board'' approach 
to sodium labeling is not based on various drug categories; it is based 
on sodium being present in any OTC drug product.
    -5. Two comments agreed with the proposal to include both active 
and inactive ingredients when labeling/calculating total sodium content 
in an OTC drug product. One comment added that all recommended diluents 
should also be included in the sodium content labeling.
    -FDA appreciates the comments' concurrence. Including all sources 
of sodium in the total sodium content labeling enables consumers to 
determine the total amount of sodium consumed, regardless of the 
source. Diluents in OTC drug products are inactive ingredients and 
would be covered by this rulemaking. Under Sec. 201.64(b) of this final 
rule, the agency is requiring the sodium content labeling of OTC drug 
products to include both active and inactive ingredients, which would 
include any diluents used in these products.
    -6. Several comments contended that the scope of covered products 
should be limited to products intended for ingestion rather than orally 
administered products. The comments argued that ``orally administered'' 
OTC drug products include dentifrices and mouthwashes that are not 
ingested, but rather expectorated. The comments pointed out any 
absorption of sodium from these products is minuscule.
    -The agency agrees that certain OTC drug products, such as 
dentifrices and mouthwashes, although orally administered, need not be 
covered by this rulemaking. These products are not intended to be 
ingested by the user, and the agency does not have sufficient 
information on the absorption of sodium when these products are used to 
warrant a labeling requirement at this time. However, orally 
administered gum or lozenge forms of OTC drug products intended for 
either partial or complete ingestion are covered by this rule. 
Therefore, in this final rule the agency is changing the language in 
Sec. 201.64(a), (c), and (d) from ``orally administered OTC drug 
products'' to ``OTC drug products intended for oral ingestion,'' and is 
adding the following sentence to Sec. 201.64(a): ``OTC drug products 
intended for oral ingestion include gum and lozenge dosage forms, but 
do not include dentifrices, mouthwashes, or mouth rinses.''
    -The agency notes that some OTC laxative and vaginal drug products 
intended for rectal or vaginal administration can contain very high 
levels of sodium from both active and inactive ingredients. Significant 
amounts of some of these products may be absorbed. At this time, the 
agency does not have sufficient information on the absorption of sodium 
from these products to warrant a labeling requirement.
    -The agency is seeking comments from interested individuals on 
whether this final rule should be amended to include sodium content 
labeling for OTC rectal laxative, vaginal, dentifrice, mouthwash, and 
mouth rinse drug products. Comments should be sent to the Dockets 
Management Branch (address above) by July 22, 1996.
    -7. Two comments suggested requiring sodium content labeling for 
prescription drugs as well as OTC drug products. The comments stated 
that this information was important for the elderly and for patients 
receiving more than one drug product. One comment added that physicians 
treating patients on sodium restricted diets need to be aware of the 
amount of sodium in prescription products.
    -The agency agrees that sodium content labeling of prescription 
drugs would be beneficial. This information would be helpful to 
physicians, pharmacists, and consumers so they can make informed 
decisions. However, prescription drug labeling is outside the scope of 
this rulemaking for OTC drug products. Currently, the agency is 
actively considering the comments' recommendation for prescription drug 
labeling and is appraising whether the problem can best be dealt with 
via a regulation, guidance document, or another approach. At this time, 
the agency encourages sodium content labeling of prescription drugs on 
a voluntary basis.

C. Comments on Sodium Content Labeling

    -8. One comment recommended that any level of sodium in OTC drug 
products be listed on the label to enable consumers to make their own 
decision as to what is an insignificant amount of sodium in relation to 
their diet. Another comment suggested that the minimum level of sodium 
requiring labeling be increased from greater than 5 mg per maximum 
recommended dose to greater than 70 mg per maximum recommended daily 
dose. The comment mentioned that data generated by the Food and 
Nutrient Board indicate that 4,000 to 5,800 mg sodium are consumed per 
capita per day. Therefore, the sodium consumed in medications provides 
only a minimal amount and does not pose the same potential risk as 
food. The comment reasoned that 70 mg is only 5 percent of the Food and 
Nutrient Board's recommended daily intake of 1.4 grams (g) sodium for 
people on sodium restricted diets. The comment contended that this 
amount of sodium would not pose a risk to consumers on a low-sodium 
diet because 70 mg does not contribute a significant amount to their 
daily intake.
    -The agency has considered the comments' suggestions and has 
decided to use 5 mg of sodium per maximum recommended dose as the basis 
for including sodium content in the labeling of OTC drug products. As 
discussed in section II.E., comment 13 of this document, the agency 
considers a sodium level below 5 mg per dose to be physiologically 
insignificant. Thus, the agency is not requiring any labeling if the 
amount of sodium in the product is below 5 mg.
    -The agency considers a 5 mg maximum recommended dose standard a 
reasonable approach, based in part on experience with OTC antacid drug 
product labeling. Although the agency believes a 70 mg labeled maximum 
daily dose standard is not unreasonable, a 5 mg maximum labeled dose is 
consistent with the antacid monograph, which has been in effect since 
1974. As discussed in the proposed rule, the existing requirement for 
OTC antacid drug products in Sec. 331.30(f) (21 CFR 331.30(f)) provides 
that the labeling include sodium content per dosage unit if it contains 
5 mg or more. This labeling requirement for OTC antacids has been in 
effect for over 20 years, and consumers are familiar with that 
approach. The sodium labeling requirements in this final rule, based on 
sodium content per dose, are similar to those in the antacid monograph.
    -The 5 mg approach will also result in more informative labeling 
than the 70 mg approach, because more products will be labeled with 
sodium content. More than 14 doses per day of a product containing less 
than 5 mg sodium per dose would be required to exceed 70 mg sodium per 
labeled maximum daily dose. Almost all OTC drug products are not taken 
that often. Thus, more products will likely require sodium content 
labeling based on 5 mg per dose than would result using 70 mg per 
labeled maximum daily dose as the basis. (See also section I.E., 
comment 13. of this document)
    -9. Three comments endorsed the agency's proposal to express the 
sodium

[[Page 17801]]

content of an OTC drug product in mg per dosage unit. The first comment 
suggested that those monographs now stating sodium labeling in 
milliequivalents (mEq) could be amended to mg. The comment stated that 
sodium declaration is more useful when provided in terms of dosage 
units (such as a teaspoonful or a tablet) than in terms of the 
recommended dosage amount, because the recommended dosage amount can 
vary. The second comment considered the option of having the sodium 
content declaration based on the recommended daily dose, but rejected 
that option because studies have shown that consumers frequently take 
more than the recommended daily dosage for OTC drug products. The third 
comment stated that the sodium content declaration should include the 
total sodium in both mg and mEq per dosage unit, average daily intake, 
and maximum recommended daily intake, if applicable.
    -The agency appreciates the comments' endorsements of the 
requirement that sodium content be listed in mg per dosage unit. The 
agency does not believe that listing some or all of the options (e.g., 
in both mg and mEq per dosage unit, per average daily intake, and per 
maximum daily intake) would be useful, because these multiple numbers 
would tend to confuse consumers and would unnecessarily clutter the 
label. Further, the agency believes consumers are more familiar with 
the term ``mg'' as used in food labeling than the term ``mEq.'' 
Therefore, in this final rule the agency is using only mg per dosage 
unit for declaring the sodium content of OTC drug products.
    -As one comment noted, other OTC drug monographs address sodium 
labeling. These monographs will be amended to delete specific sodium 
labeling requirements so that the sodium labeling of all OTC drug 
products will appear in a single regulation. In the proposed rule for 
sodium labeling, the agency proposed to delete the existing 
requirements for OTC antacid drug products that appear in 
Sec. 331.30(c)(5) and (f) (56 FR 19224 to 19225). The agency is 
finalizing that in this final rule. The sodium labeling requirements 
proposed in Sec. 334.50(b)(5) and (b)(8) of the tentative final 
monograph for OTC laxative drug products (50 FR 2124 at 2153, January 
15, 1985) and proposed in Sec. 343.50(c)(1)(viii)(A) and 
(c)(1)(viii)(B) and Sec. 343.50(c)(2)(viii)(A) and (c)(2)(viii)(B) of 
the tentative final monograph for OTC internal analgesic, antipyretic, 
and antirheumatic drug products (53 FR 46204 at 46256 to 46257, 
November 16, 1988) will be deleted when the final monographs for those 
drug classes are issued in a future issue of the Federal Register.
    -10. One comment requested that the agency require sodium content 
information to be presented in a predetermined place on the OTC drug 
product label, such as the ingredients list. The comment gave an 
example of a product containing a level of sodium requiring a warning 
while, at the same time, its label prominently displayed ``75% less 
sodium than (a comparable product)'' under active ingredients. The 
actual sodium content was listed at the end of a long paragraph of 
warnings and would make the product off-limits to an individual on a 
sodium-restricted diet. The comment contended that such labeling could 
potentially mislead consumers.
    -FDA agrees that the sodium content of an OTC drug product should 
be expressed at a specific location on the product label. By 
designating a specific location, consumers can find the sodium content 
of the product more quickly and with less confusion because the 
information will appear in the same location in the labeling of all 
orally ingested OTC drug products. The agency believes the most logical 
place for the sodium content labeling is at the end of the ingredients 
section. Further, the sodium content should be listed on a separate 
line after the heading 'Sodium Content' so that it is easily recognized 
by the consumer. Accordingly, the agency is amending proposed 
Sec. 201.64(b) in this final rule to add a sentence that states: ``The 
sodium content per dosage unit shall be listed on a separate line after 
the heading 'Sodium Content' as the last statement in the ingredients 
section.''
    -11. One comment suggested that product labeling state a 
recommended safe range of sodium intake to provide consumers with a 
baseline for the control of sodium consumption.
    -The comment's request for labeling to advise consumers of a safe 
level of sodium is impractical because different medical and 
physiological problems require different levels of sodium restriction. 
Consumers should consult with physicians or other health professionals 
to determine the optimum levels of sodium consumption for their 
particular conditions. Thus, FDA is not requiring that the labeling 
state a recommended safe range of sodium intake at this time.

D. Comments on Sodium Warning Labeling

    -12. Two comments contended that the agency's proposal to include a 
sodium warning in the labeling of OTC drug products when the maximum 
recommended daily dose contains more than 140 mg of sodium is 
inconsistent with the labeling of foods, which does not require 
warnings at any level. The comments questioned the choice of 140 mg per 
maximum recommended daily dose as the level that triggers the sodium 
warning. The comments argued that the warning may unnecessarily confuse 
or alarm consumers. The first comment contended that the choice of 140 
mg is completely arbitrary and questioned its scientific relevance. The 
comment stated that there is no evidence that consumers derive a 
significant percentage of sodium intake from OTC drug products.
    -The second comment stated that 140 mg of sodium is markedly lower 
than the level required to effect an increase in blood pressure. 
Asserting that OTC drugs are intended for short term use, the comment 
said intermittent use of such products will not affect the long-term 
benefit of a low-sodium diet because the resulting increase in blood 
pressure is rapidly reversed upon discontinuation of the product. The 
comment contended that the sodium warning, if required, should be based 
on ``per dose'' or ``per dosage unit,'' rather than ``maximum 
recommended daily dose,'' because a single dose more closely resembles 
a single serving, the unit used for food labeling. The comment also 
contended that the readability of the label will be compromised as the 
label becomes more cluttered, and that additional warnings of 
questionable value will only reduce the impact of other warnings on the 
label.
    -Noting that the sodium warning represents a familiar cautionary 
signal for consumers, a third comment stated that sodium-containing 
drugs could contribute a significant percentage of the daily sodium 
intake for some individuals. The comment mentioned that 1,000 mg of 
sodium per day is common for sodium restricted diets and that 140 mg of 
sodium represents 14 percent of the daily allowance for such diets. 
Several comments argued that sodium warnings should be considered on a 
case-by-case basis. (See section II.B., comment 4 of this document.)
    -FDA is establishing, where possible, uniformity in labeling 
between foods and OTC drug products. FDA recognizes that OTC drug 
products containing greater than 140 mg of sodium require a warning, 
while foods do not require a warning at any level of sodium. The 
labeling requirements for drugs need to be somewhat different from 
those for foods because of the differences in

[[Page 17802]]

consumption patterns. (See section II.A., comment 2 of this document.) 
The agency considers the labeling approach in this final rule 
appropriate, even though it is not the same as that for foods in all 
respects.
    -The choice of 140 mg as the level of sodium above which a warning 
should be required is not, as one comment contended, completely 
arbitrary. In a survey conducted by the agency and discussed in the 
final rule for declaration of sodium content and label claims for foods 
on the basis of sodium content (49 FR 15510 at 15519, April 18, 1984), 
it was found that over 50 percent of the foods surveyed contained less 
than 140 mg of sodium per serving. Thus, the agency determined that a 
substantial portion of the food supply is eligible to bear the ``low 
sodium'' descriptive term. By establishing 140 mg as an upper limit for 
the term ``low sodium'' for OTC drug products and requiring a warning 
for products containing sodium above that level, consumers can more 
easily monitor their total daily sodium intake. Requiring a warning for 
products below the 140 mg level could be confusing to consumers because 
some products containing the term ``low-sodium'' could, at the same 
time, contain the warning. FDA believes that a warning requirement for 
OTC drug products that contain more than 140 mg sodium would not 
unnecessarily confuse or alarm consumers, as two comments suggested. As 
another comment stated, the sodium warning represents a familiar 
cautionary signal for consumers. The agency concludes that the warning 
requirement will be welcomed by those who want to monitor their sodium 
intake.-
    -The agency considers a numeric value that can be readily converted 
from mg to mEq useful for dietary planning, because physicians and 
dietitians sometimes calculate sodium in mEq rather than mg when 
prescribing sodium restrictions (49 FR 15510 at 15519). One mEq of 
sodium is equivalent to 23 mg. Thus, the 140 mg sodium level is 
approximately 6 mEq, allowing for easy calculation. The comments did 
not provide any evidence that warnings based on some other level of 
sodium would be more informative or useful to consumers than the 140 mg 
level proposed by the agency.
    -The agency agrees with one comment's contention that an OTC drug 
containing 140 mg of sodium is well below the level needed to affect 
blood pressure. However, it is the total amount of sodium consumed from 
all sources, both foods and drugs, that must be considered. As one 
comment pointed out, 140 mg represents 14 percent of a common (1,000 
mg) sodium-restricted diet. The agency considers the level of sodium 
found in some OTC drug products, such as antacids, to be significant 
for people on low- sodium diets, especially if the drug product is 
taken in multiple daily doses as most antacids are. While many 
consumers do not derive significant amounts of sodium from OTC drug 
products, many others do. The agency concludes that it is important to 
provide information to those consumers who can be adversely affected by 
the sodium content of OTC drug products.
    -The agency disagrees with one comment's suggestion that the 
warning, if required, should be based on ``per dose,'' rather than on 
``maximum recommended daily dose.'' Drug products are often taken in 
multiple doses in 1 day, while many different foods are more likely to 
be consumed only once a day. Thus, by equating one serving of food to 
one dose of drug, the intake per day for a drug would be a multiple of 
the amount in one dose, while the intake per day for a food may be only 
the amount found in a single serving of food. Because low-sodium diets 
are based on the total amount of sodium consumed in 1 day, the agency 
believes it is appropriate to base the sodium warning threshold on the 
labeled maximum daily dose.
    -The agency shares the comment's concern about readability of the 
label and avoiding unnecessary clutter. However, the agency considers a 
warning for OTC drug products containing appreciable amounts of sodium 
important to alert those consumers who wish or need to minimize their 
sodium intake. Therefore, in this final rule the agency is providing 
for a mandatory warning for all OTC drug products intended for oral 
ingestion containing more than 140 mg sodium per labeled maximum daily 
dose.

E. Comments on Use of Descriptive Terms in Sodium Labeling

    - 13. One comment supported the intent of the sodium labeling 
proposal, but asserted that the term ``sodium free'' should be 
prohibited on drugs containing any sodium. The comment stated that 
labeling should be reliable and not mislead consumers as to the sodium 
content of OTC drug products. The comment contended that most consumers 
expect products labeled as ``sodium free'' to contain no sodium, but 
this would not be true if ``sodium free'' products were allowed to 
contain up to less than 5 mg of sodium. The comment mentioned health 
concerns about high blood pressure related to sodium, and argued that 
inaccurate labeling adversely impacts consumer purchasing decisions. 
The comment acknowledged that agency regulations for food allow 
products with less than 5 mg of sodium per serving to be labeled as 
``sodium free.'' The comment requested that the existing food 
regulations and the proposed OTC drug regulations be modified to 
prohibit the use of the term ``sodium free'' on food and drug products 
containing any sodium.
    -The agency has considered the comment's request and concludes that 
the term ``sodium free'' should only be used for products containing 
``0 mg'' sodium, as defined in this final rule. Thus, the level of 
sodium in OTC drug products for which the term ``sodium free'' proposed 
in Sec. 201.64(d) may be used is being changed from ``less than 5 
milligrams per maximum recommended daily dose'' to ``0 milligrams per 
labeled maximum daily dose'' in this final rule. The agency's basis for 
the term ``sodium free'' in the proposed rule for sodium labeling of 
OTC drug products (56 FR 19222 at 19223) was based on the sodium 
labeling regulation for foods in Sec. 101.61(b)(1)(i) (21 CFR 
101.61(b)(1)(i)), which provides for the voluntary use of ``sodium 
free'' in the labeling of foods containing less than 5 mg sodium per 
serving. Most foods naturally contain at least trace amounts of sodium 
and the amount of sodium in a given food can vary. The agency concluded 
that the 5 mg sodium level for food is, practically speaking, a 
nonsignificant amount of dietary sodium.
    -However, in contrast to foods in which sodium may occur naturally, 
the amount of sodium in OTC drug products can be controlled during the 
manufacturing process. With today's analytical methodology, sodium can 
be accurately measured in parts per million. Thus, the agency believes 
consumers expect labels of drug products to accurately and reliably 
convey the level of ingredients in the product. While there may be no 
need to inform consumers of minute amounts of sodium (e.g., this final 
rule requires sodium content labeling only for those products 
containing 5 or more mg sodium per recommended dose), there is also no 
reason to label a product as ``sodium free'' when, in fact, it contains 
more than ``0 mg'' of sodium, as defined in this final rule.
    -In Sec. 201.64(b) of this final rule, sodium content labeling is 
rounded-off to the nearest whole number as mg per dosage unit. Thus, a 
product containing less than 0.5 mg sodium per dosage unit could be 
labeled as ``0 mg'' sodium and

[[Page 17803]]

a product containing more than 0.5 mg and less than 1.5 mg sodium could 
be labeled as ``1 mg'' sodium. The agency believes that the term 
``sodium free'' should not be used in the labeling of OTC drug products 
except for those products that contain ``0 mg'' sodium per labeled 
maximum daily dose. Thus, a product containing 0.4 mg sodium per tablet 
or teaspoon (rounded-off to 0) with labeling to take one tablet or 
teaspoon daily may use the descriptive term ``sodium free'' in its 
labeling. However, when the recommended dose in an OTC drug monograph 
provides for more than one dosage unit per day, e.g., the directions 
advise to take one or two tablets (or teaspoons) or to take two tablets 
(or teaspoons), the same product containing 0.4 mg sodium (rounded-off 
to 0) per tablet or teaspoon could not use the term ``sodium free'' 
because the labeled maximum dose contains 0.8 mg (rounded-off to 1). 
The labeling set forth in this final rule also eliminates the 
possibility that products labeled ``sodium free'' will at the same time 
be labeled with a sodium content greater than ``0 mg,'' a potential 
basis for consumer confusion.
    -Similarly, the agency determined that the term ``alcohol free'' 
may not be used in the labeling of OTC drug products that contain any 
alcohol (see the Federal Register of March 13, 1995, 60 FR 13590). In 
Sec. 328.50(e) (21 CFR 328.50(e)) the agency requires: ``For a product 
to state in its labeling that it is 'alcohol free,' it must contain no 
alcohol (0 percent).''
    -Therefore, in this final rule, the agency is providing under 
Sec. 201.64(d) for the voluntary use of the term ``sodium free'' if the 
amount of sodium in the labeled maximum daily dose is ``0 mg.'' The 
agency recognizes that this position differs from that for nutrition 
labeling for foods, but believes that, for OTC drug product labeling, 
it is more appropriate. Any request to change the existing ``sodium 
free'' labeling for food products in Sec. 101.61(b)(1)(i) should be 
made in a citizen petition, in accord with Sec. 10.30 (21 CFR 10.30).
    -14. One comment recommended a relative print size limit on 
descriptive terms for sodium content to ensure that the primary 
emphasis of the OTC drug product label remains on the medical 
indication of the product. The comment stated that a consumer's 
foremost reason for purchasing an OTC drug product should be based on 
its medical indication, not on its sodium content.
    -FDA agrees with the comment that a relative print size limit on 
descriptive terms would be useful to help ensure that consumers are not 
distracted from the medical purpose of the product. The food 
regulations (21 CFR 103.13(f)) provide that a nutrient content claim 
shall be in a type size no larger than two times the statement of 
identity and shall not be unduly prominent in type style compared to 
the statement of identity. The agency believes that a related approach 
should also be used for OTC drug products.
    -The agency does not believe that the print size of the descriptive 
terms for sodium labeling for OTC drug products should be any larger 
than the print size of the statement of identity. Allowing larger print 
size (e.g., two times the size of that for the statement of identity, 
as for nutrient claims) could result in label clutter or misplaced 
emphasis. OTC drug products are generally marketed in smaller packages 
than foods and, thus, have less label space available than food 
products. Accordingly, the agency is adding in Sec. 201.64(h) of this 
final rule the following statement:
    The terms ``sodium free,'' ``very low sodium,'' and ``low sodium'' 
shall be in print size and style no larger than the product's statement 
of identity and shall not be unduly prominent in print size or style 
compared to the statement of identity.
    -15. One comment stated that descriptive terms in sodium labeling 
of OTC drug products will help improve consumer understanding of the 
message, and that the terms must be in simple language for lay persons 
to understand. Another comment contended that voluntary descriptive 
terms are unnecessary, often confusing, and potentially misleading. The 
comment suggested the proposed terms ``sodium free,'' ``very low 
sodium,'' and ``low sodium'' could translate into ``healthy'' and 
thereby become misleading. Further, the comment questioned using these 
descriptive terms in conjunction with the required warning, arguing 
that an inconsistent jump occurs from 140 mg (maximum daily dosage as 
``low sodium'') to 141 mg (maximum daily dosage requiring a warning). 
The comment concluded that these two diverse measurements would prime 
the consumer for confusion.
    -The agency believes the voluntary descriptive terms ``sodium 
free,'' ``very low sodium,'' and ``low sodium'' are simple for 
consumers to understand. The terms are not intended to convey the exact 
level of sodium in a product, only an approximation. The comment did 
not provide any evidence that consumers might misinterpret these terms 
as meaning ``healthy,'' specifically as they relate to OTC drug product 
labeling. The agency recognizes that the jump for the maximum daily 
dose from 140 mg, representing ``low sodium,'' to 141 mg, requiring a 
warning, is not ideal. However, many standards have a set criterion, 
above or below which some action is triggered. The agency concludes 
there is no evidence to believe that these preset levels will lead to 
consumer confusion. (See also section II.A., comment 2 of this 
document.)

F. Comments on the Sodium-Hypertension Relationship

    16. One comment considered it inappropriate for the agency to adopt 
regulations that address only sodium intake without reference to the 
anion (chloride). The comment urged that FDA regulations reflect the 
``emerging learning that the chloride ion is a necessary causative 
element in salt-induced hypertension.'' The comment referenced 16 
studies (Ref. 1) to show that both the sodium and chloride ions play 
roles in inducing hypertension in some persons, and that other sodium 
salts do not induce hypertension.
    -The comment stated that a report by the National Academy of 
Sciences/National Research Council (Ref. 2) on diet and health 
correlated dietary ``salt'' or ``sodium chloride,'' rather than 
``sodium,'' with hypertension. The comment added that recent medical 
surveys reflect the growing understanding that both the sodium and the 
chloride ions play roles in causing salt-sensitive hypertension. For 
example, the comment cited the Yearbook of Medicine (Ref. 3) as stating 
that ``it remains to be established that any commonly ingested sodium 
salt other than sodium chloride can increase blood pressure in patients 
with salt-sensitive essential hypertension.''
    -A second comment also contended that the effects of sodium on 
blood pressure are limited to sodium in the form of sodium chloride. 
The comment provided literature references (Ref. 4) suggesting that 
when the accompanying anion was other than chloride, sodium intake did 
not affect blood pressure. The comment mentioned that sodium in drug 
products is usually present as the benzoate, phosphate, or citrate 
salt, and contended that there is no clear evidence that the sodium 
content of the drug presents a hazard sufficient to deem the proposed 
warning appropriate.
    One comment, which approved of sodium content labeling but was 
opposed to the warning, mentioned a submission made in response to 
FDA's request for scientific data and information to determine if a 
scientific basis exists for health claims relating to sodium and 
hypertension (Ref. 5). In that submission, the comment concluded that 
there are no well-

[[Page 17804]]

documented scientific data supporting a clear relationship between 
dietary sodium and hypertension applicable to the general public. The 
comment claimed that recent scientific evidence shows that a reduced 
sodium diet does not reduce the risk of hypertension in healthy 
individuals, but that it may contribute to heart disease and additional 
health risks. The comment concluded that appropriate scientific 
evidence does not exist to support any general health claims based on a 
relationship between sodium and hypertension.
    -The comment subsequently provided current articles and reviews on 
the salt-blood pressure relationship (Ref. 6). The comment emphasized 
one article (Ref. 7) that addressed the question of whether and how 
sodium chloride intake influences blood pressure. The authors stated 
that past literature was interpreted as ``demonstrating a strong 
relationship between salt intake and blood pressure, a substantial 
benefit to all hypertensive persons of reduced salt intake, and a 
relatively low risk to society of promulgating this policy.'' Based on 
more recent studies, the authors suggested that only a portion (30 to 
40 percent) of adults are salt (sodium chloride) sensitive and that 
salt sensitivity is linked to other cations and anions in the diet 
(e.g., adequate potassium and calcium intake may protect against salt 
sensitivity). The comment contended that because of new and mounting 
evidence that low-sodium diets may present some risk to individuals who 
are not salt-sensitive hypertensives, FDA should not require the sodium 
warning. Although opposed to the warning, the comment agreed that some 
individuals need to monitor their sodium intake.
    -The agency agrees with the comments that the sodium ion is not the 
only influence on hypertension. The question of whether or not the 
chloride ion is necessary for sodium to increase blood pressure is an 
academic issue. Even if chloride or another ion in addition to sodium 
is necessary to elevate blood pressure, hypertension is not the sole 
reason for this rulemaking. There are other conditions for which 
physicians recommend low-sodium diets. For instance, sodium bicarbonate 
reportedly exacerbates congestive heart failure. While sodium chloride 
is the primary source of sodium in the general population, sodium 
bicarbonate and other sodium-containing ingredients can account for a 
considerable amount of sodium in OTC drug products. Sodium labeling is 
not aimed specifically at patients with hypertension, but is intended 
to benefit all people who need or wish to monitor their sodium intake 
for whatever reason. The comments made no mention of the effect of 
sodium on any aspects of health other than hypertension.
    -This rulemaking does not state a causal relationship between 
sodium and hypertension, but rather provides for sodium content 
labeling and recommends that individuals on a low-sodium diet consult a 
physician if daily doses of greater than 140 mg sodium are to be 
ingested. This final rule provides that the labeling of OTC drug 
products include the total sodium content (including both active and 
inactive ingredients). It is reasonable for consumers on low-sodium 
diets to consult with their physician before taking OTC drug products 
with a high sodium content. The physician can put the variables into 
perspective and decide whether specific OTC drug products should be 
used. Alternative products containing less or no sodium may be 
available.
    -The agency has previously considered the relationship of sodium 
and hypertension and agrees that this is a complex subject that 
deserves more study. The agency recognizes that there are differences 
of opinion on this subject. Nonetheless, in a final rule on food 
labeling (health claims and labeling statements; sodium and 
hypertension), the agency stated ``based on the totality of the 
scientific evidence, there is significant agreement among qualified 
experts that diets high in sodium are associated with high blood 
pressure'' (58 FR 2820 at 2822, January 6, 1993). The agency stated 
that some studies indicate that sodium chloride and other sodium salts 
have distinct effects on blood pressure (58 FR 2829). Sodium chloride 
is the major source of sodium in foods and most studies investigating 
the effect of sodium on hypertension have involved either increasing or 
decreasing sodium chloride intake. The agency acknowledged that if it 
is true that sodium chloride, and not sodium, is implicated in high 
blood pressure, products containing other sources of sodium may be 
incorrectly considered to promote high blood pressure. The agency 
allowed the optional term ``salt'' to be used in addition to ``sodium'' 
in health claims in food labeling. However, the agency noted there is 
not significant scientific agreement that only sodium chloride affects 
blood pressure (58 FR 2829). Therefore, the basis for health claims 
relating to hypertension in that final rule was sodium content, not 
sodium chloride content.
    -FDA recognizes that not all individuals need to or should reduce 
their sodium intake. Sodium consumed from OTC drug products alone may, 
for most individuals, be insignificant and may not cause a significant 
increase in blood pressure. However, OTC drug products are not a 
consumer's sole source of sodium. All sources of sodium must be taken 
into account when monitoring daily intake. Even though, as one comment 
suggested, some individuals may need counseling from physicians or 
dietitians in order to maintain a strict low-sodium diet, the agency 
considers the sodium warning for OTC drug products helpful even for 
those individuals. This rulemaking does not recommend specific levels 
of sodium intake for the general population or for individuals h 
specific conditions. However, for those who need or want to monitor 
their sodium intake, the agency concludes that sodium content and 
warning labeling for OTC drug products is useful.

 References

     (1) Comment No. C00017, Docket No. 90N-0309, Dockets Management 
Branch.
     (2) Committee on Diet and Health, National Academy of Sciences/
National Research Council (U.S.), Diet and Health: Implications for 
Reducing Chronic Disease Risk, National Academy Press, Washington, 
1989.
     (3) D. E. Rogers et al., editors, Yearbook of Medicine, 
Yearbook Medical Publishers, Inc., Chicago, pp 589-590, 1989.
    -(4) Comment No. C00014, Docket No. 90N-0309, Dockets Management 
Branch.
    -(5) Comment No. C00007, Docket No. 91N-0095, Dockets Management 
Branch.
    -(6) Comment No. SUP 1, Docket No. 90N-0309, Dockets Management 
Branch.
    -(7) Muntzel, M., and T. Drueke, ``A Comprehensive Review of the 
Salt and Blood Pressure Relationship,'' American Journal of 
Hypertension, 5:1S-42S, 1992.

III. Summary of Significant Changes from the Proposed Rule

    -1. In this final rule, the agency is revising Sec. 201.64(b) to 
eliminate the 5-mg rounding-off provision. The final rule requires that 
the sodium content be rounded-off to the nearest whole number, whatever 
the content, per dosage unit. (See section II.A., comment no. 3 of this 
document.)
    -2. The agency is changing the language in Sec. 201.64(a) and (c) 
through (f) from ``orally administered OTC drug products'' to ``OTC 
drug products intended for oral ingestion,'' and is adding the 
following sentence to Sec. 201.64(a): ``OTC drug products intended for 
oral ingestion include gum and lozenge dosage forms, but do not include 
dentifrices, mouthwashes, or mouth rinses.'' (See section II.B., 
comment no. 6 of this document.)
    -3. The agency is adding the following in Sec. 201.64(b): ``The 
sodium content per

[[Page 17805]]

dosage unit shall be listed on a separate line after the heading 
`Sodium Content' as the last statement in the ingredients section.'' 
(See section II.C., comment no. 10 of this document.)
    -4. Proposed Sec. 201.64(d) provided for the voluntary use of the 
term ``sodium free'' for products containing ``less than 5 milligrams'' 
of sodium in the maximum recommended daily dose. This final rule allows 
for the use of the term ``sodium free'' only for those products 
containing ``0 mg'' of sodium in the labeled maximum daily dose. The 
agency is revising the example in proposed Sec. 201.64(d) to clarify 
the basis for use of descriptive terms, taking into account the 
rounding-off provision for the sodium content in mg per dosage unit to 
the nearest whole number. (See section II.A., comment no. 3; section 
II.E., comment no. 13; and part III.1 of this document.)
    -5. The agency has added a provision in Sec. 201.64(h) of this 
final rule limiting the print size and style of the ``sodium free,'' 
``very low sodium,'' and ``low sodium'' terms to no larger than and not 
unduly prominent in comparison to the product's statement of identity. 
(See section II.E., comment no. 14 of this document.)

IV. The Agency's Final Conclusions on Sodium Labeling-

    FDA believes that the public interest in and the public health 
consequences of sodium intake have produced a need for more informative 
and consistent sodium content labeling information on drugs and foods. 
This is true for individuals with hypertension, heart failure, or other 
conditions who must monitor their sodium intake.
    -To establish uniform content declarations, warnings, and 
descriptive terms for sodium in foods and OTC drug products, the agency 
is implementing the following requirements for OTC drug products 
intended for oral ingestion: (1) The product must have a sodium content 
declaration if it contains five mg or more of sodium per single labeled 
dose (which may involve one or more dosage units, e.g., tablets, 
teaspoons). (2) The product must bear a sodium warning if it contains 
more than 140 mg (about 6 mEq) of sodium in the labeled maximum daily 
dose. This warning states: ``Do not use this product if you are on a 
sodium-restricted diet unless directed by a doctor.'' (3) Manufacturers 
may use the following descriptive terms for sodium content: ``Sodium-
free'' for products containing 0 mg sodium in the labeled maximum daily 
dose; ``very low sodium'' for products containing 35 mg or less; and 
``low sodium'' for products containing 140 mg or less. The requirement 
for a sodium content declaration is based on the number of mg of sodium 
in one dose, while the requirement for a warning statement and the use 
of the optional descriptive terms are based on the number of mg of 
sodium in the labeled maximum daily dose.
    -Because consumers and health professionals are accustomed to 
computing sodium intake in mg (49 FR 15510 at 15530), and to provide 
for uniformity in the declaration of sodium content labeling for foods 
and OTC drug products intended for oral ingestion, the term 
``milligrams'' or the abbreviation ``mg'' is used to designate the 
sodium content of OTC drug products. The total sodium content 
(including both active and inactive ingredients), in mg per dosage 
unit, should be rounded-off to the nearest whole number. If the single 
recommended dose (one or more dosage units) of the product contains 5 
mg or more of sodium, a declaration of sodium content expressed in mg 
per single dosage unit (e.g., tablet, teaspoon) is required to be 
listed on a separate line after the heading ``Sodium Content'' as the 
last statement in the ingredients section.
    -The new sodium labeling requirements apply to all OTC drugs 
intended for oral ingestion, whether marketed under an OTC drug 
monograph, an approved application, or no application. The existing 
requirements relating to sodium labeling in Sec. 331.30(c)(5) and (f) 
of the final monograph for OTC antacid drug products are being deleted. 
The proposed sodium labeling requirements being considered in other 
ongoing OTC drug rulemakings will be deleted when final monographs for 
those drug classes are issued in a future issue of the Federal 
Register.

V. Analysis of Impacts

    -An analysis of the costs and benefits of this regulation, 
conducted under Executive Order 12291 was discussed in the proposed 
rule (56 FR 19222 at 19225). No comments were received in response to 
the agency's request for specific comment on the economic impact of 
this rulemaking. Executive Order 12291 has been superseded by Executive 
Order 12866.
    -FDA has examined the impacts of the final 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 final rule is consistent with the regulatory philosophy and 
principles identified in the Executive Order. In addition, the final 
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. With this final rule, one-time label modification 
costs associated with changing product labels will be incurred by some 
manufacturers. FDA estimates those costs to total less than $500,000 
for the entire industry. This projected cost is based on estimates of 
the number of products that will be affected by this final rule, the 
number of distinct label changes that will be required, and the cost of 
printing new labels.
    -OTC antacid drug products are the primary products having a 
significant number of orally administered active ingredients containing 
sodium. The monograph for those products has been in effect since 1974 
and these products currently bear sodium labeling. For these products, 
the labeling change will involve a slight change in wording, resulting 
only in a minor cost to have a labeling revision printed. In almost all 
cases, manufacturers can routinely revise labeling at the next printing 
so that minimal costs should be incurred. Manufacturers will have up to 
12 months after publication of this final rule in the Federal Register 
to revise their product labeling. FDA anticipates that most antacid 
drug products would undergo a label printing within a 12-month period. 
Because these OTC antacid drug products already bear sodium labeling 
warnings, the agency may extend the time period beyond 12 months, if 
necessary, upon request, for the revised wording to be implemented.
    -Other OTC drug products (i.e., laxatives and internal analgesics) 
having a few sodium-containing active ingredients affected by this 
final rule previously were not required to bear sodium labeling. These 
products will need to have new labels printed to incorporate the sodium 
labeling. These products must also have new labeling printed in the 
future when the final monographs for OTC laxative and internal 
analgesic drug products are published. This again involves one-time 
label modification costs. For products undergoing such labeling 
changes, the incremental costs attributable to this rule for sodium 
labeling will be

[[Page 17806]]

negligible. A limited number of OTC laxative and internal analgesic 
drug products contain sodium-containing active ingredients. Tentative 
final monographs with sodium labeling requirements for these products 
have been published, and no adverse comments concerning economic 
impacts have been received in response to the proposals. The agency is 
not aware of any significant number of other OTC drug products that 
will be affected due to the sodium content of inactive ingredients. Use 
of the descriptive terms for sodium set forth in this rulemaking is 
voluntary. Therefore, any implementation of these terms could be done 
by a manufacturer at any time that new labeling is ordered. The agency 
finds that the cost of adding one of these descriptive terms to the 
product's labeling will be negligible. Accordingly, the agency 
certifies that the 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 
warning statement and the sodium terms 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)). The sodium content per dosage unit is product 
formulation information that manufacturers have on hand as part of 
their usual and customary business practice.

VII. 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 nor an environmental impact statement is 
required.

List of Subjects

21 CFR Part 201

    -Drugs, Labeling, Reporting and recordkeeping requirements.

21 CFR Part 331

    -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, title 
21 of the Code of Federal Regulations is amended in parts 201 and 331 
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. 201.64 is added to subpart C to read as follows:

Sec. 201.64   Sodium labeling.

    -(a) The labeling of over-the-counter (OTC) drug products intended 
for oral ingestion shall contain the sodium content per dosage unit 
(e.g., tablet, teaspoonful) if the sodium content of a single 
recommended dose of the product (which may be one or more dosage units) 
is 5 milligrams or more. OTC drug products intended for oral ingestion 
include gum and lozenge dosage forms, but do not include dentifrices, 
mouthwashes, or mouth rinses.
    -(b) The sodium content shall be expressed in milligrams per dosage 
unit and shall include the total amount of sodium regardless of the 
source, i.e., from both active and inactive ingredients. The sodium 
content shall be rounded-off to the nearest whole number. The sodium 
content per dosage unit shall be listed on a separate line after the 
heading ``Sodium Content'' as the last statement in the ingredients 
section.
    -(c) The labeling of OTC drug products intended for oral ingestion 
shall contain the following warning under the heading ``Warning'' (or 
``Warnings'' if it appears with additional warning statements) if the 
amount of sodium present in the labeled maximum daily dose of the 
product is more than 140 milligrams: ``Do not use this product if you 
are on a sodium-restricted diet unless directed by a doctor.''
    -(d) The term ``sodium free'' may be used in the labeling of OTC 
drug products intended for oral ingestion if the amount of sodium in 
the labeled maximum daily dose is 0 milligram. For example, a product 
containing 0.4 (rounded-off to zero (0)) milligram sodium per tablet 
with directions to take one tablet daily may use the term ``sodium 
free'' in its labeling. However, when the recommended dose provides for 
taking more than one dosage unit per day, e.g., take one or two 
tablets, or take two tablets, the same product containing 0.4 milligram 
sodium per tablet shall not use the term ``sodium free'' because the 
labeled maximum daily dose contains 0.8 milligram sodium.
    -(e) The term ``very low sodium'' may be used in the labeling of 
OTC drug products intended for oral ingestion if the amount of sodium 
in the labeled maximum daily dose is 35 milligrams or less.
    -(f) The term ``low sodium'' may be used in the labeling of OTC 
drug products intended for oral ingestion if the amount of sodium in 
the labeled maximum daily dose is 140 milligrams or less.
    -(g) The term ``salt'' is not synonymous with the term sodium and 
shall not be used interchangeably or substituted for the term 
``sodium.''
    -(h) The terms ``sodium free,'' ``very low sodium,'' and ``low 
sodium'' shall be in print size and style no larger than the product's 
statement of identity and shall not be unduly prominent in print size 
or style compared to the statement of identity.
    -(i) Any product subject to this paragraph that is not labeled as 
required by this paragraph and that is initially introduced or 
initially delivered for introduction into interstate commerce after 
April 22, 1997, is misbranded under sections 201(n) and 502(a) and (f) 
of the Federal Food, Drug, and Cosmetic Act.

PART 331--ANTACID PRODUCTS FOR OVER-THE-COUNTER (OTC) HUMAN USE

    -3. The authority citation for 21 CFR part 331 continues to read as 
follows:

    -Authority: Secs. 201, 501, 502, 503, 505, 510, 701 of the 
Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 351, 352, 353, 
355, 360, 371).


Sec. 331.30   [Amended]

    -4. Section 331.30 Labeling of antacid products is amended by 
removing paragraph (c)(5) and redesignating paragraphs (c)(6) and 
(c)(7) as paragraphs (c)(5) and (c)(6), respectively, and by removing 
paragraph (f) and redesignating paragraph (g) as paragraph (f).

    Dated: March 30, 1996.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 96-9735 Filed 4-19-96; 8:45 am]
BILLING CODE 4160-01-F