Labeling of Orally Ingested Over-the-Counter Drug Products Containing Calcium, Magnesium, and Potassium

SUMMARY: The Food and Drug Administration (FDA) is proposing to amend

the general labeling provisions for over-the-counter (OTC) drug

products to require that the labeling of all OTC drug products intended

for oral ingestion include the calcium content per dosage unit when the

product contains 20 milligrams (mg) or more per single dose; a warning

statement that persons with kidney stones and persons on a calcium-

restricted diet should not take the product unless directed by a doctor

when the product contains more than 3.2 grams (g) of calcium in the

labeled maximum daily dose; the magnesium content per dosage unit when

the product contains 8 mg or more per single dose; a warning statement

that persons with kidney disease and persons on a magnesium-restricted

diet should not take the product unless directed by a doctor if the

product contains more than 600 mg magnesium in the labeled maximum

daily dose; the potassium content per dosage unit when the product

contains 5 mg or more per single dose; and a warning statement that

persons with kidney disease and persons on a potassium-restricted diet

should not take the product unless directed by a doctor if the product

contains more than 975 mg potassium in the labeled maximum daily dose.

The agency is proposing that the calcium, magnesium, and potassium

content be labeled in mg per dosage unit, rounded to the nearest whole

number. FDA is issuing this notice of proposed rulemaking in order to

provide uniform calcium, magnesium, and potassium content and warning

labeling for all OTC drug products intended for oral ingestion whether

marketed under an OTC drug monograph, an approved application, or no

application.

DATES: Written comments by July 22, 1996. Written comments on the

agency's economic impact determination by July 22, 1996. The agency is

proposing that any final rule based on this proposal be effective 12

months after the date of its publication in the Federal Register.

ADDRESSES: Submit 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

A. Calcium

In the advance notice of proposed rulemaking for OTC antacid drug

products (38 FR 8714 at 8718, April 5, 1973), the Advisory Review Panel

on OTC Antacid Drug Products (Antacid Panel) concluded that calcium

carbonate is safe when taken in a dosage of not more than 160

milliequivalents (mEq) of calcium (8 g calcium carbonate) per day. The

Antacid Panel stated that hypercalcuria in response to calcium

ingestion is not rare in the population and the danger of renal stone

formation has to be considered in determining the intake of calcium-

containing antacids.

The maximum daily dose for calcium carbonate or calcium phosphate

in Sec. 331.11(d) (21 CFR 331.11(d)) of the antacid monograph is 160

mEq (e.g., 3.2 g calcium). This amount of calcium is contained in 8.0 g

calcium carbonate, 18.7 g monobasic calcium phosphate, and 8.3 g

tribasic calcium phosphate. The warning in Sec. 331.30(c)(1) (21 CFR

331.30(c)(1)) states: ``Do not take more than (maximum recommended

daily dosage

* * *) in a 24-hour period, or use the maximum dosage of this product

for more than 2 weeks, except under the advice and supervision of a

physician.''

In the advance notice of proposed rulemaking for OTC digestive aid

drug products (47 FR 454 at 469, January 5, 1982), the Advisory Review

Panel on OTC Miscellaneous Internal Drug Products (Miscellaneous

Internal Panel) stated that adverse reactions associated with calcium

carbonate, including alkalosis, hypercalcemia, acid rebound, milk-

alkali syndrome, and constipation, usually occur with ingestion of

larger than recommended doses and/or with chronic ingestion. The

Miscellaneous Internal Panel stated that some antacids decrease the

effectiveness of many other drugs. The Miscellaneous Internal Panel

recommended the following labeling for drug products containing calcium

carbonate: (1) ``If you are taking other drugs, consult your physician

as this drug may interfere with their effectiveness,'' and (2) ``Do not

take for longer than 2 weeks or in greater than recommended amounts,

except on the advice of a physician.'' However, these warnings were

never finalized because no calcium salt attained monograph status as an

active ingredient for use as an OTC digestive aid drug product.

B. Magnesium

In the advance notice of proposed rulemaking for OTC antacid drug

products (38 FR 8714 at 8719), the Antacid Panel stated that in normal

renal function it is difficult to reach excessive magnesium blood

levels via the oral route, because magnesium enters and leaves the

cells rapidly. However, the Antacid Panel stated that hypermagnesemia

toxicity may occur in renal dysfunction and therefore a warning is

necessary. The Antacid Panel concluded that for those products in which

the maximal daily dose exceeds 50 mEq of magnesium, the labeling should

state: ``Do not use this product if you have kidney disease except

under the advice and supervision of a physician.''

In the final monograph for OTC antacid drug products (39 FR 19862

at 19868, June 6, 1974), the agency noted that at some of its early

meetings the Antacid Panel initially considered 150 mEq per day of

magnesium as the level for requiring a warning, but upon

reconsideration reduced the amount to 50 mEq. The Antacid Panel gave

several reasons for lowering this level: (1) The normal individual

consumes from 20 to 40 mEq of magnesium per day and about one-third of

that amount is absorbed into the body; (2) if a person is taking a

magnesium-containing antacid, approximately 15 to 30 percent of that

magnesium is absorbed, and (3) if a person does not have normal renal

function, it is possible to have hypermagnesemia toxicity, i.e., the

level of magnesium in the body may reach a toxic level.

The final monograph for OTC antacid drug products includes a

warning in Sec. 331.30(c)(4) for products containing more than 50 mEq

of magnesium in the recommended daily dosage, which states: ``Do not

use this product except under the advice and supervision of a physician

if you have kidney disease.'' Although persons with normal renal

function can easily tolerate more than 50 mEq of magnesium a day, the

agency included this warning in the monograph because large doses of an

antacid could present a serious problem for

[[Page 17808]]

individuals with reduced renal function.

In the advance notice of proposed rulemaking for OTC laxative drug

products (56 FR 12902 at 12905, March 21, 1975), the Advisory Review

Panel on OTC Laxative, Antidiarrheal, Emetic, and Antiemetic Drug

Products (Laxative Panel) stated that OTC laxative drug products

containing more than 50 mEq (600 mg) magnesium in the maximum

recommended daily dose should include a warning which states that

people with kidney disease should not use the product except under the

advice and supervision of a physician. In the Federal Register of

January 15, 1985 (50 FR 2124 at 2153), the agency published a tentative

final monograph for OTC laxative drug products that included the

warning recommended by the Laxative Panel. This rulemaking has not been

completed at this time.

In the advance notice of proposed rulemaking for OTC digestive aid

drug products (47 FR 454 at 471), the Miscellaneous Internal Panel

stated that high serum magnesium levels may result from magnesium

ingestion by persons with kidney damage. The Miscellaneous Internal

Panel agreed with the Antacid Panel that a warning statement should be

present on any magnesium hydroxide preparation (47 FR 470) and on any

magnesium trisilicate preparation (47 FR 471) for which the maximal

daily dose exceeds 50 mEq (600 mg) of magnesium. The Miscellaneous

Internal Panel also stated that magnesium hydroxide has the potential

for drug interactions with certain anticoagulants and antibiotics.

Similarly, the Miscellaneous Internal Panel noted that magnesium

trisilicate absorbs various alkaloids and antibiotics in vitro.

However, this warning was never finalized because no magnesium salt

attained monograph status as an active ingredient for use as an OTC

digestive aid drug product.

C. Potassium

In the advance notice of proposed rulemaking for OTC antacid drug

products (38 FR 8714 at 8719), the Antacid Panel stated that

hyperkalemia is rare for normal persons who can easily tolerate the

potassium content of antacid drug products. The Antacid Panel

concluded, however, that potassium can accumulate in the body of

persons with impaired renal function and exert toxic effects. The

Antacid Panel recommended the following warning for products containing

more than 25 mEq (975 mg) potassium in the maximum recommended daily

dose: ``Do not use this product if you have kidney disease except under

the advice and supervision of a physician.'' This warning appears in

Sec. 331.30(c)(6) of the antacid final monograph, slightly rephrased to

read: ``Do not use this product except under the advice and supervision

of a physician if you have kidney disease.''

In the advance notice of proposed rulemaking (56 FR 12902 at

12905), the Laxative Panel recommended that if a laxative product

contains more than 25 mEq (975 mg) of potassium in the maximum

recommended daily dose, the labeling should advise consumers with

kidney disease not to use the product except under the advice and

supervision of a physician. The agency is aware that some effervescent

laxative drug products contain significant amounts of potassium as

inactive ingredients. The Laxative Panel recommended that the inactive

ingredients be listed (with or without the amounts) for OTC laxative

drug products and that the availability of sodium, potassium, and

magnesium in the maximum recommended daily dose be stated in the

labeling. The Laxative Panel noted that certain inactive ingredients

(including calcium hydroxide and potassium carbonate) are added to some

laxative preparations to enhance their formulation or to contribute to

the effervescent qualities.

In the tentative final monograph for OTC laxative drug products (50

FR 2124 at 2153), the agency agreed with the Laxative Panel's

recommendation and proposed the following warning for those products

containing more than 975 mg potassium in the maximum recommended daily

dose: ``Do not use this product if you have kidney disease unless

directed by a doctor.'' This rulemaking has not been completed at this

time.

D. Rulemaking for Sodium Labeling of OTC Drug Products

The agency has already addressed sodium labeling in a final rule

published elsewhere in this issue of the Federal Register. That rule

amends the general labeling provisions for OTC drug products to include

sodium labeling and provides for across-the-board uniform sodium

content and warning labeling for all OTC drug products intended for

oral ingestion. New Sec. 201.64 requires sodium content labeling of all

products containing 5 mg or more sodium per single recommended dose and

requires that products containing more than 140 mg sodium per maximum

recommended daily dose be labeled with a general warning that states:

``Do not use this product if you are on a sodium-restricted diet unless

directed by a doctor.'' Section 201.64 also provides for the voluntary

use of certain descriptive terms (``sodium free,'' ``very low sodium,''

and ``low sodium''). These descriptive terms are the same terms used to

describe sodium content in food labeling.

Sodium content is expressed in mg per single dosage unit (e.g.,

tablet, teaspoonful), rounded-off to the nearest whole number, and

includes the total amount of sodium regardless of the source (both

active and inactive ingredients). OTC drug products ``intended for oral

ingestion'' also include gum and lozenge dosage forms, but do not

include dentifrices, mouthwashes, or mouth rinses. Because some OTC

drug products not intended for oral administration can contain very

high levels of sodium that may be absorbed from both active and

inactive ingredients, the agency has asked for comments from interested

individuals on whether the final rule should be amended to include

sodium labeling for OTC rectal, vaginal, dentifrice, mouthwash, and

mouth rinse drug products. The agency will address this subject in a

future issue of the Federal Register.

Two comments received to the tentative final monograph for OTC

laxative drug products contended that sodium labeling of OTC laxative

and other drug products should be consistent with FDA's food labeling

terminology. The comments stated that food products already bear FDA

terminology and the food terminology will become the dominant system.

Thus, other mandatory FDA labeling systems should be made consistent

with that system. The agency has used this approach in the final rule

for sodium labeling of OTC drug products published elsewhere in this

issue of the Federal Register.

E. Food Labeling Regulations

FDA regulations for food products address calcium and magnesium

labeling. Section 101.9 (21 CFR 101.9) requires the labeling of food

products to declare the content, as a percent of the Reference Daily

Intake (RDI), of calcium, iron, vitamin C, and vitamin E. Other

vitamins and minerals for which a RDI has been established, including

magnesium, may be listed voluntarily, unless they are added as a

nutrient supplement or a claim is made about them, in which case they

must be declared.

Section 101.9(c)(5) provides for the voluntary declaration of

potassium content in a labeled serving size. However, when a claim is

made about potassium, the declaration is mandatory and is placed on the

nutrition label

[[Page 17809]]

immediately following the sodium content. When the potassium content is

less than 5 mg per serving, the content is expressed as zero.

Vitamins and minerals, other than calcium, iron, vitamin C, and

vitamin E, present at less than 2 percent of the RDI are not required

to be declared in nutrition labeling but may be declared as zero or by

use of an asterisk referring to a footnote that states, ``Contains less

than 2% of the Daily Value of this (these) nutrient (nutrients)''

(Sec. 101.9(c)(8)(iii)). The RDI for calcium is 1,000 mg and for

magnesium is 400 mg (Sec. 101.9(c)(8)(iv)). Thus, for foods containing

less than 20 mg of calcium per serving, a declaration of zero is

required on the nutrition label. For foods containing less than 8 mg of

magnesium per serving, content declaration is not required (unless a

claim is made about the nutrient) or may be declared as zero or as less

than 2 percent of the Daily Value.

The regulations in Sec. 101.36(b)(3) (21 CFR 101.36(b)(3)) for

nutrition labeling of dietary supplements of vitamins and minerals

require that potassium be declared except when present in quantitative

amounts by weight that allow a declaration of zero.

The regulations for health claims related to calcium and

osteoporosis in Sec. 101.72(c)(2)(i)(E) (21 CFR 101.72(c)(2)(i)(E))

require the labeling of food products to state that a total dietary

intake greater than 2,000 mg of calcium has no further known benefit to

bone health. This requirement applies when the food or supplement

contains more than 400 mg of calcium per reference amount. A recently

published NIH Concensus Statement on optimal calcium intake states that

up to a total intake of 2,000 mg per day appears to be safe in most

individuals (``Optimal Calcium Intake,'' NIH Consensus Statement,

12(4):1-31, June 6-8, 1994).

II. The Agency's Tentative Conclusions on Labeling of Orally

Ingested OTC Drug Products Containing Calcium, Magnesium, and

Potassium

A. Basis for Rulemaking -

FDA believes that the public interest in, and the public health

consequences of, calcium, magnesium, and potassium intake have produced

a need for more informative and consistent labeling information for

these ingredients in OTC drug products. The agency believes certain

labeling requirements are needed to alert persons with renal failure,

kidney stones, or other conditions, and persons taking other

medications who wish to monitor their intake of calcium, magnesium, and

potassium. Consumers need to consider their intake from foods, dietary

supplements, and drugs. Therefore, the agency is proposing calcium,

magnesium, and potassium content and warning labeling for all OTC drug

products intended for oral ingestion that contain certain levels of

these ingredients (including both active and inactive ingredients).

B. Criteria for Content and Warning Labeling-

In order to establish uniform content declarations and warnings

relating to calcium, magnesium, and potassium for orally ingested OTC

drug products and to establish content labeling similar to that used in

food labeling, the agency is proposing to adopt: (1) 20 mg of calcium,

8 mg of magnesium, and 5 mg of potassium as the amount per single

recommended dose in an OTC drug product (which may involve one or more

dosage units, e.g., tablets, teaspoonsful, etc.) that requires a

content declaration; and (2) 3.2 g calcium, 600 mg magnesium, and 975

mg potassium as the amounts present in the maximum labeled daily dose

above which a warning is required. The agency is therefore proposing to

amend the general drug labeling provisions in part 201 (21 CFR part

201) to include these labeling requirements for OTC drug products

intended for oral ingestion.

The proposed levels for requiring content labeling are similar to

those used in food labeling. In contrast, the proposed levels for

requiring warnings are based on recommendations of FDA advisory review

panels in the early 1970's. The agency acknowledges that there may be

more recent scientific information to consider in setting requirements

for OTC drug product labeling. The agency specifically encourages

comment and data on this aspect of the proposal.

C. Basis for Amount Requiring Content Labeling

1. Calcium and Magnesium Content-

As stated in section I.E. of this document, a serving of food

containing 20 mg or more of calcium requires a content declaration, and

a serving of food containing 8 mg or more of magnesium (if added as a

supplement or if a claim is made) requires a content declaration in the

nutrition labeling of foods. Thus, the agency is using 20 mg calcium

and 8 mg magnesium per single recommended dose as the amounts at which

OTC drug products should include content labeling for these

ingredients.

2. Potassium Content

As noted in section I.E. of this document, potassium labeling for

foods is optional unless a claim is made about the potassium content;

but, if declared, it is expressed in mg per serving for those foods

containing 5 mg or more. In Sec. 201.64(a) of the final rule for sodium

labeling of OTC drug products, the agency required a declaration of the

sodium content for all OTC drugs intended for oral ingestion if the

sodium content per single recommended dose is 5 mg or more. The agency

believes it is not necessary to declare potassium amounts below 5 mg

per dose. However, the agency believes it is appropriate to declare the

potassium content if the product contains 5 mg or more per single

recommended dose.

D. Basis for Amount Requiring Warning Statements

The agency believes that for uniformity in labeling, warnings

should be required across-the-board for calcium, magnesium, and

potassium for those OTC drug products intended for oral ingestion

containing a certain concentration of these ingredients.

1. Calcium Warning

Based on the current requirements in the monograph for OTC antacid

drug products and the recommendations of the Miscellaneous Internal

Panel (see section I.A. of this document), the agency is proposing to

require the following warning for all OTC drug products containing more

than 3.2 g calcium (equivalent to 8 g calcium carbonate) per labeled

maximum daily dose: ``Do not use this product if you have kidney stones

or if you are on a calcium-restricted diet unless directed by a

doctor.'' The NIH Consensus Statement on optimal calcium intake

suggests that a 2,000 mg total daily intake is safe, but it does not

give a definitive conclusion as to what level is unsafe. When the 3,200

mg daily dosage level, proposed as the level requiring a warning, is

added to the 1,000 mg recommended daily intake that may be included in

a person's diet, the resulting 4,200 mg daily intake is considerably

higher than the 2,000 mg level found to be safe in the NIH consensus

statement. The agency invites comments on whether the proposed 3.2 g

level requiring a warning should be lowered.

2. Magnesium Warning

The agency is proposing to require the following warning for all

OTC drug products that contain more than 600 mg magnesium per labeled

maximum daily dose: ``Do not use this product if you have kidney

disease or if you are on a

[[Page 17810]]

magnesium-restricted diet unless directed by a doctor.'' This warning

is similar to the warning in Sec. 331.30(c)(4) of the final monograph

for OTC antacid drug products.

3. Potassium Warning

The agency is proposing to require the following warning for all

OTC drug products that contain more than 975 mg potassium per maximum

recommended dose: ``Do not use this product if you have kidney disease

or if you are on a potassium-restricted diet unless directed by a

doctor.'' This warning is similar to the warning in Sec. 331.30(c)(6)

of the final monograph for OTC antacid drug products.

E. Units of Measure-

The agency believes the units of measure, where possible, should be

similar for foods and drugs. The unit of measure in declaring the

content of these components in foods is mg or g per serving of food.

While a serving of food is not the same as a dosage of a drug, the

agency believes it is logical to declare the content in mg per dosage

unit of the drug and to require a content declaration if the ingredient

per dose (which could be contained in one or more active or inactive

ingredients and in one or more dosage units) is equal to the amount in

a serving of food that requires a declaration in the nutrition

labeling. This is similar to the agency's approach in the final rule

for sodium labeling of OTC drug products. Section 201.64(b) states:

``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.''

F. Rounding to Whole Number

While the food labeling regulations allow for the content

declaration of certain ingredients (e.g., sodium and potassium) to be

labeled as ``zero'' up to a certain level (5 mg per serving)

(Sec. 101.9(c)(8)(i) and (c)(8)(ii)), the agency believes these

ingredients in drugs should not be labeled as zero content except when

the content is zero (based on rounding to the nearest whole number, as

in the regulation for sodium labeling of OTC drug products). As

discussed in the sodium labeling final rule, most OTC drug products are

manufactured and the concentration of ingredients can be strictly

controlled. Thus, the concentration of specific ingredients is expected

to be less variable in OTC drug products than in foods. For consistency

in labeling, the agency believes the labeling of these ingredients

should be expressed in mg per dosage unit rounded to the nearest whole

number for those products containing less than 1 g. For those products

containing 1 g or more per dosage unit, the content labeling may be

rounded to the nearest tenth of a g.

G. Implementation of Labeling Requirements

The agency encourages manufacturers to comply voluntarily with the

provisions of this proposed rule despite the fact that revisions in the

requirements may occur in the final rule in response to submitted

comments. Should any manufacturer choose to adopt the labeling

described in this proposed rule, and should any revisions occur in the

final rule, the agency will permit the use of existing stocks of labels

for those products labeled according to the proposed rule for a period

of 1 year following publication of the final rule.

Should this proposed amendment to part 201 relating to calcium,

magnesium, and potassium content and warning labeling of all OTC drug

products intended for oral ingestion be published as a final rule, then

the existing requirements relating to magnesium labeling in

Sec. 331.30(c)(4) and potassium labeling in Sec. 331.30(c)(5) of the

final monograph for OTC antacid drug products and the proposed labeling

requirements for magnesium and potassium being considered in other

ongoing OTC drug rulemakings will be deleted. The agency advises that

on or after 12 months after publication of a final rule any OTC drug

product subject to this rule that does not meet these labeling

requirements and that is initially introduced or initially delivered

for introduction into interstate commerce will be misbranded under

sections 201(n) and 502(a) and (f) of the Federal Food, Drug, and

Cosmetic Act (21 U.S.C. 321(n) and 352(a) and (f)).

III. Analysis of Impacts

FDA has examined the impacts of the proposed rule under Executive

Order 12866 and the Regulatory Flexibility Act (Pub. L. 96-354).

Executive Order 12866 directs agencies to assess all costs and benefits

of available regulatory alternatives, and when regulation is necessary,

to select regulatory approaches that maximize net benefits (including

potential economic, environmental, public health and safety, and other

advantages; distributive impacts; and equity). The agency believes that

this proposed rule is consistent with the regulatory philosophy and

principles identified in the Executive Order. In addition, the proposed

rule is not a significant regulatory action as defined by the Executive

Order and, thus, is not subject to review under the Executive Order.

The Regulatory Flexibility Act requires agencies to analyze

regulatory options that would minimize any significant impact of a rule

on small entities. Should this proposed rule become a final rule, one-

time label modification costs associated with changing product labels

would 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 the proposed 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

calcium, magnesium, and potassium. The monograph for those products has

been in effect since 1974 and these products currently bear magnesium

and potassium warning labeling. For these products, the labeling change

would involve a slight change in wording, resulting only in a minor

cost to have a labeling revision printed. For those products containing

calcium, a new warning would be required in product labeling. In almost

all cases, this revision would be routinely done at the next labeling

printing so that minimal costs should be incurred. Manufacturers will

have up to 12 months after publication of a final rule in the Federal

Register to revise their product labeling. It is anticipated that most

antacid drug products would undergo a label printing within a 12-month

period. Products containing magnesium and potassium would need only

minor revisions, and products containing calcium would need to add some

new labeling.

Other OTC drug products (i.e., antidiarrheals, laxatives, and

internal analgesics) having one or a few calcium, magnesium, and

potassium-containing active ingredients that would be affected by

mandatory calcium, magnesium, and potassium labeling currently are not

required to bear the labeling recommended in this proposed rule. These

products would need to have new labels printed to incorporate the

labeling requirements of this rulemaking. These products will also need

to have new labeling printed in the future when the final monographs

for OTC antidiarrheal, laxative, and internal analgesic drug products

are published. This again involves one-time label modification costs.

For products that will be undergoing such labeling

[[Page 17811]]

changes, the incremental costs attributable to this rule for calcium,

magnesium, and potassium labeling would be negligible. A limited number

of OTC antidiarrheal, laxative, and internal analgesic drug products

contain calcium, magnesium, and potassium-containing active

ingredients.

Accordingly, the agency certifies that the proposed rule will not

have a significant economic impact on a substantial number of small

entities. Therefore, under the Regulatory Flexibility Act, no further

analysis is required.

The agency invites public comment regarding any substantial or

significant economic impact that this rulemaking would have on OTC drug

products intended for oral ingestion. Types of impact may include, but

are not limited to, costs associated with relabeling, repackaging, or

reformulating. Comments regarding the impact of this rulemaking on OTC

drug products should be --accompanied by appropriate documentation. A

period of 90 days from the date of publication of this proposed

rulemaking in the Federal Register will be provided for comments on

this subject to be developed and submitted. The agency will evaluate

any comments and supporting data that are received and will reassess

the economic impact of this rulemaking in the preamble to the final

rule.

IV. Paperwork Reduction Act of 1995

FDA tentatively concludes that the labeling requirements proposed

in this document are not subject to review by the Office of Management

and Budget because they do not constitute a ``collection of

information'' under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501

et seq.). Rather, the proposed warning statements are a ``public

disclosure of information originally supplied by the Federal government

to the recipient for the purpose of disclosure to the public'' (5 CFR

1320.3(c)(2)). The calcium, magnesium, and potassium content per dosage

unit is product formulation information that manufacturers have on hand

as part of their usual and customary business practice.

V. 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.

VI. Request for Comments

Interested persons may, on or before July 22, 1996, submit to the

Dockets Management Branch (address above) written comments regarding

this proposal. Written comments on the agency's economic impact

determination may be submitted on or before July 22, 1996. Three copies

of all comments are to be submitted, except that individuals may submit

one copy. Comments are to be identified with the docket number found in

brackets in the heading of this document and may be accompanied by a

supporting memorandum or brief. Received comments may be seen in the

office above between 9 a.m. and 4 p.m., Monday through Friday.

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, it is

proposed that title 21 of the Code of Federal Regulations be 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. 201.70 is added to subpart C to read as follows:

Sec. 201.70 Calcium labeling.

(a) The labeling of over-the-counter (OTC) drug products intended

for oral ingestion shall contain the calcium content per dosage unit

(e.g., tablet, teaspoonful) if the calcium content of a single

recommended dose of the product (which may be one or more dosage units)

is 20 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 calcium content shall be expressed in milligrams or grams

per dosage unit and shall include the total amount of calcium

regardless of the source, i.e., from both active and inactive

ingredients. If less than 1 gram, milligrams should be used. The

calcium content shall be rounded-off to the nearest whole number in

milligrams (or tenth of a gram if over 1 gram) and shall be listed on a

separate line after the heading ``Calcium Content'' as the last

sentence 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 calcium present in the labeled maximum daily dose of the

product is more than 3.2 grams: ``Do not use this product if you have

kidney stones or if you are on a calcium-restricted diet unless

directed by a doctor.''

(d) 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

(date 1 year after publication of the final rule), is misbranded under

sections 201(n) and 502(a) and (f) of the Federal Food, Drug, and

Cosmetic Act.

3. New Sec. 201.71 is added to subpart C to read as follows:

Sec. 201.71 Magnesium labeling.

(a) The labeling of over-the-counter (OTC) drug products intended

for oral ingestion shall contain the magnesium content per dosage unit

(e.g., tablet, teaspoonful) if the magnesium content of a single

recommended dose of the product (which may be one or more dosage units)

is 8 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 magnesium content shall be expressed in milligrams or grams

per dosage unit and shall include the total amount of magnesium

regardless of the source, i.e., from both active and inactive

ingredients. If less than 1 gram, milligrams should be used. The

magnesium content shall be rounded-off to the nearest whole number in

milligrams (or tenth of a gram if over 1 gram) and shall be listed on a

separate line after the heading ``Magnesium Content'' as the last

sentence 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 magnesium present in the labeled maximum daily dose of the

product is more than 600 milligrams: ``Do not use this product if

[[Page 17812]]

you have kidney disease or if you are on a magnesium-restricted diet

unless directed by a doctor.''

(d) 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

(date 1 year after publication of the final rule), is misbranded under

sections 201(n) and 502(a) and (f) of the Federal Food, Drug, and

Cosmetic Act.

4. New Sec. 201.72 is added to subpart C to read as follows:

Sec. 201.72 Potassium labeling.

(a) The labeling of over-the-counter (OTC) drug products intended

for oral ingestion shall contain the potassium content per dosage unit

(e.g., tablet, teaspoonful) if the potassium 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 potassium content shall be expressed in milligrams or grams

per dosage unit and shall include the total amount of potassium

regardless of the source, i.e., from both active and inactive

ingredients. If less than 1 gram, miligrams should be used. The

potassium content shall be rounded-off to the nearest whole number in

milligrams (or tenth of a gram if over 1 gram) and shall be listed on a

separate line after the heading ``Potassium 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 potassium present in the labeled maximum daily dose of the

product is more than 975 milligrams: ``Do not use this product if you

have kidney disease or if you are on a potassium-restricted diet unless

directed by a doctor.''

(d) 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

(date 1 year after publication of the final rule), 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

5. 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]

6. Section 331.30 Labeling of antacid products is amended by

removing paragraphs (c)(4) and (c)(5) and by redesignating paragraph

(c)(6) as paragraph (c)(4).

Dated: March 30, 1996.

William K. Hubbard,

Associate Commissioner for Policy Coordination.

[FR Doc. 96-9734 Filed 4-19-96; 8:45 am]

BILLING CODE 4160-01-F