27886 Federal Register / Vol. 63, No. 98 /Thursday, May 21, 1998 / Proposed Rules

(301) 504–0800 or delivered to the

Office of the Secretary, Room 501, 4330

East-West Highway, Bethesda, Maryland

20814. Copies should be submitted in

five copies and captioned ‘‘Sleepwear

Policy Statement.’’ Comments may also

be filed by telefacsimile to (301) 504–

0127 or by e-mail to cpsc os@cpsc.gov.

FOR FURTHER INFORMATION CONTACT:

Patricia Fairall, Program Manager,

Office of Compliance, Consumer

Product Safety Commission,

Washington, D.C. 20207; telephone

(301) 504–0400, extension 1369.

SUPPLEMENTARY INFORMATION:

A. Background

The Consumer Product Safety

Commission enforces two flammability

standards for children’s sleepwear. The

flammability standard for children’s

sleepwear in sizes 0 through 6X is

codified at 16 CFR Part 1615. The

flammability standard for children’s

sleepwear in sizes 7 through 14 is

codified at 16 CFR Part 1616.

On September 9, 1996, the

Commission issued a final rule

amending the flammability standards

for children’s sleepwear to exclude from

the definition of ‘‘children’s sleepwear,’’

codified at 16 CFR 1615.1(a) and

1616.2(a), (1) garments sized for infants

nine months of age or younger and (2)

tight-fitting garments for children older

than nine months. 61 FR 47634. The

Commission found that such tightfitting garments did not present an

unreasonable risk of injury. Rather, the

Commission’s information showed that

many severe incidents occurred with

loose-fitting garments such as oversized

t-shirts used inappropriately as

sleepwear. The Commission concluded

that garments fitting closely and that

touch the body at key points should be

exempt from the sleepwear standards

because they do not present the same

risk as loose-fitting garments. These

amendments became effective on

January 1, 1997. However, the

Commission also issued a stay of

enforcement for close-fitting garments

which are labeled and promoted as

underwear. That stay expires on June 9,

1998.

B. Clarification

The Commission has become aware

that the garment industry is concerned

about the policy statements in 16 CFR

1615.64(d) and 1616.65(d), which

suggest segregation of items covered by

the children’s sleepwear standards from

all fabrics and garments that are beyond

the scope of the children’s sleepwear

standards. The purpose of the

September 9, 1996 final rule was to

allow garments sized for a child nine

months and under and tight-fitting

garments in sizes above nine months to

be sold and used as sleepwear.

Therefore, the Commission proposes to

modify the policy statements at

1615.64(d) and 1616.65(d) to provide

that infant garments (defined in the

amended sleepwear standard at 16 CFR

1615.1(c)(1) as sized for a child nine

months and under) and ‘‘tight-fitting’’

garments (defined in the amended

sleepwear standard at 16 CFR 1615.1(o)

and 1616.2(m)) can be marketed and

promoted with other sleepwear.

For the reasons stated above and

pursuant to the authority of Section 4 of

the Flammable Fabrics Act (15 U.S.C.

1193), the Commission proposes to

amend 16 CFR 1615.64 and 1616.65 to

read as follows:

PART 1615—STANDARD FOR THE

FLAMMABILITY OF CHILDREN’S

SLEEPWEAR: SIZES 0 THROUGH 6X

1. The authority citation for part 1615

continues to read as follows:

Authority: Sec. 4, 67 Stat. 112, as

amended, 81 Stat. 569–70; 15 U.S.C. 1193.

2. Section 1615.64 is amended by

revising paragraph (d) introductory text

to read as follows:

§ 1615.64 Policy to clarify scope of the

standard.

* * * * *

(d) Retailers, distributors, and

wholesalers, as well as manufacturers,

importers, and other persons (such as

converters) introducing a fabric or

garment into commerce which does not

meet the requirements of the

flammability standards for children’s

sleepwear, have an obligation not to

promote or sell such fabric or garment

for use as an item of children’s

sleepwear. Also, retailers, distributors,

and wholesalers are advised not to

advertise, promote, or sell as an item of

children’s sleepwear any item which a

manufacturer, importer, or other person

(such as a converter) introducing the

item into commerce has indicated by

label, invoice, or, otherwise, does not

meet the requirements of the children’s

sleepwear flammability standards and is

not intended or suitable for use as

sleepwear. ‘‘Infant garments’’ as defined

by § 1615.1(c) and ‘‘tight-fitting’’

garments as defined by § 1615.1(o) are

exempt from the standard which

requires flame resistance. They may be

marketed as sleepwear for purposes of

this section. Additionally, retailers are

advised:

* * * * *

PART 1616—STANDARD FOR THE

FLAMMABILITY OF CHILDREN’S

SLEEPWEAR: SIZES 7 THROUGH 14

1. The authority citation for part 1616

continues to read as follows:

Authority: Sec. 4, 67 Stat. 112, as

amended, 81 Stat. 569–70; 15 U.S.C. 1193.

2. Section 1616.65 is amended by

revising paragraph (d) introductory text

to read as follows:

§ 1616.65 Policy scope of the standard.

* * * * *

(d) Retailers, distributors, and

wholesalers, as well as manufacturers,

importers, and other persons (such as

converters) introducing a fabric or

garment into commerce which does not

meet the requirements of the

flammability standards for children’s

sleepwear, have an obligation not to

promote or sell such fabric or garment

for use as an item of children’s

sleepwear. Also, retailers, distributors,

and wholesalers are advised not to

advertise, promote, or sell as an item of

children’s sleepwear any item which a

manufacturer, importer, or other person

(such as a converter) introducing the

item into commerce has indicated by

label, invoice, or, otherwise, does not

meet the requirements of the children’s

sleepwear flammability standards and is

not intended or suitable for use as

sleepwear. ‘‘Tight-fitting’’ garments as

defined by § 1616.2(m) are exempt from

the standard which requires flame

resistance. They may be marketed as

sleepwear for purposes of this section.

Additionally, retailers are advised:

* * * * *

Dated: May 12, 1998.

Sadye E. Dunn,

Secretary, Consumer Product Safety

Commission.

[FR Doc. 98–13028 Filed 5–20–98; 8:45 am]

BILLING CODE 6355–01–P

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Part 334

[Docket No. 78N–036L]

RIN 0910–AA01

Laxative Drug Products for Over-theCounter Human Use; Proposed

Amendment to the Tentative Final

Monograph

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice of proposed rulemaking.
Federal Register / Vol. 63, No. 98 /Thursday, May 21, 1998 / Proposed Rules 27887

1The Panel designated this ingredient ‘‘sodium

biphosphate.’’ However, monobasic sodium

phosphate is currently the official name for this

ingredient in the USP Dictionary of USAN and

International Drug Names, 1997.

2The Panel designated this ingredient ‘‘sodium

phosphate.’’ However, dibasic sodium phosphate is

currently the official name for this ingredient in the

USP Dictionary of USAN and International Drug

Names, 1997.

3Sodium phosphates oral solution is the official

name for a solution of dibasic sodium phosphate

and monobasic sodium phosphate in the U.S.

Pharmacopeia 23/National Formulary 18, 1995.

4Sodium phosphates enema is the official name

for a solution of dibasic sodium phosphate and

monobasic sodium phosphate in the U.S.

Pharmacopeia 23/National Formulary 18, 1995.

SUMMARY: The Food and Drug

Administration (FDA) is amending the

tentative final monograph for over-thecounter (OTC) laxative drug products to

include additional general and

professional labeling for oral and rectal

dibasic sodium phosphate/monobasic

sodium phosphate (sodium phosphates)

drug products. FDA is proposing new

warnings and directions for these

products and a new time to effect

statement for rectal products based on

new data submitted after publication of

the tentative final monograph for OTC

laxative drug products. This proposal is

part of the ongoing review of OTC drug

products conducted by FDA. Elsewhere

in this issue of the Federal Register the

agency is finalizing the package size

limitation and warning prior to the

completion of the final monograph for

OTC laxative drug products.

DATES: Submit written comments or

objections by August 19, 1998.

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:

Cheryl A. Turner, Center for Drug

Evaluation and Research (HFD–560),

Food and Drug Administration, 5600

Fishers Lane, Rockville, MD 20857,

301–827–2222.

SUPPLEMENTARY INFORMATION:

I. Background

In the Federal Register of March 21,

1975 (40 FR 12902), FDA published,

under 21 CFR 330.10(a)(6), an advance

notice of proposed rulemaking to

establish a monograph for OTC laxative,

antidiarrheal, emetic, and antiemetic

drug products, together with the

recommendations of the Advisory

Review Panel on OTC Laxative,

Antidiarrheal, Emetic, and Antiemetic

Drug Products (the Panel), which was

the advisory review panel responsible

for evaluating data on the active

ingredients in these classes. The Panel

recommended monograph status for

phosphate salts, such as sodium

biphosphate 1 and sodium phosphate 2

(40 FR 12902 at 12940).

The agency’s proposed regulation, in

the form of a tentative final monograph,

for OTC laxative drug products was

published in the Federal Register of

January 15, 1985 (50 FR 2124). The

agency also proposed monograph status

for sodium phosphates oral solution 3.

(See proposed § 334.58(d)(5)(i), 50 FR

2124 at 2152 and 2155.) In addition to

its use as an OTC laxative for the relief

of occasional constipation, sodium

phosphates oral solution is used as part

of a bowel cleansing regimen in

preparing a patient for surgery or for

preparing the colon for x-ray or

endoscopic examination. (See proposed

§ 334.80(a)(2), 50 FR 2124 at 2157.)

Sodium phosphates oral solution and

sodium phosphates enema 4,

respectively, are the current United

States Pharmacopeia (USP) names for

the oral and rectal dosage forms of the

combination of sodium phosphates

ingredients.

In the Federal Register of March 31,

1994 (59 FR 15139), the agency

proposed to amend the tentative final

monograph for OTC laxative drug

products to limit the OTC container size

for sodium phosphates oral solution to

not greater than 90 milliliters (mL). The

agency noted that the major trade

product containing sodium phosphates

oral solution was marketed in 45-mL,

90-mL, and 240-mL bottles. The

purgative dose or dose used for

colonoscopy is 45 mL. Because the

product was available in three sizes, the

manufacturer’s labeling advised

physicians to prescribe by volume and

not to prescribe by the bottle and not to

exceed the recommended dosage, as

serious side effects may occur. Despite

this labeling, the multiple container

sizes available in the marketplace have

caused consumer confusion and appear

to have been involved in several

consumer deaths (59 FR 15139 at

15140).

Because of the reported cases of

accidental overdosing and the confusion

that has occurred between 240-mL and

90-mL container sizes, the agency

proposed that the 240-mL size container

of sodium phosphates oral solution

should no longer remain in the OTC

marketplace. In the interest of safety, the

agency proposed to limit the maximum

OTC container size for this product to

90 mL.

The agency proposed to include the

package size limitation and a warning

(informing consumers not to exceed the

recommended dosage unless directed by

a doctor) in the monograph for OTC

laxative drug products. However, that

monograph has not been finalized to

date. Because of the potential serious

safety risk involved, elsewhere in this

issue of the Federal Register the agency

is finalizing the package size limitation

and warning prior to the completion of

the final monograph for OTC laxative

drug products. The agency is including

this information in part 201 (21 CFR

part 201) at this time and will

incorporate it into the final monograph

for OTC laxative drug products at a later

date.

Based on new data submitted since

the January 15, 1985, and the March 31,

1994, proposals were published, the

agency is proposing in this document

additional general and professional

labeling for oral and rectal sodium

phosphates products for OTC laxative

use. In the Federal Register of February

27, 1997 (62 FR 9024), FDA proposed to

establish a standardized format for the

labeling of OTC drug products. When

the agency finalizes that proposal, the

agency will also amend the final version

of the rule proposed herein, as needed,

to conform to the final labeling rule.

Copies of previous rulemakings

discussed above and information that

has come to the agency’s attention since

publication of the proposals are on

public display in the Dockets

Management Branch (address above).

II. The Agency’s Labeling Proposals for

Sodium Phosphates

A. Introduction

One comment informed the agency of

modifications made in the labeling of its

rectal enema sodium phosphates

product. The comment had expanded

the professional labeling to include

additional warning statements regarding

use in patients with a colostomy,

congenital megacolon, imperforate anus,

impaired renal function, heart disease,

congestive heart failure, preexisting

electrolyte disturbances (such as

dehydration or those secondary to the

use of diuretics), or in patients using

calcium channel blockers, diuretics, or

other medications that may affect

electrolyte levels, as hypocalcemia,

hyperphosphatemia, hypernatremia,

and acidosis may occur. The comment

cited several references (Refs. 1, 2, and

3) to support its warning statements.

The professional labeling also included

information on the treatment of

electrolyte imbalances. The comment

stated that the labeling no longer

recommends the use of this enema

product in children under 2 years of

age. The comment mentioned that a

summarized version of the professional
27888 Federal Register / Vol. 63, No. 98 /Thursday, May 21, 1998 / Proposed Rules

labeling will appear on the product’s

retail carton.

The agency agrees with the comment

that the professional labeling for these

sodium phosphates products should be

expanded to include more information

for health professionals to ensure safe

use. As a result of the comment’s

additional warnings, the agency has

reevaluated all of the labeling for

sodium phosphates products (oral and

rectal). The agency notes that the

comment included calcium channel

blockers in its professional warning.

However, the agency is not aware of any

specific data to show that sodium

phosphates products should not be used

in patients taking calcium channel

blockers. Therefore, calcium channel

blockers will not be included in the

professional warning for sodium

phosphates products at this time.

B. Professional Labeling

In § 334.80(b)(2) of the tentative final

monograph for OTC laxative drug

products (50 FR 2124 at 2157), the

agency proposed the following warnings

in the professional labeling for products

containing sodium phosphates: ‘‘Do not

use in patients with megacolon, as

hypernatremic dehydration may occur.

Use with caution in patients with

impaired renal function.’’ The

comment’s labeling and information in

the literature provide a basis to expand

this warning. Individuals with impaired

renal function (Refs. 4 through 8,

including the elderly (Ref. 5)), heart

disease (Refs. 8, 9, and 10), acute

myocardial infarction (Refs. 11 and 12),

unstable angina (Ref. 12), dehydration

(Refs. 1 and 9), or who are on diuretics

(Ref. 10) are at risk for an electrolyte

imbalance to occur with use of oral and

rectal sodium phosphates products.

Sodium phosphates can cause

alterations in serum levels of sodium,

potassium, phosphate, chloride, and

calcium and, in some people, such

changes can be life threatening. The

reduction of calcium levels reflects

changes in ionized calcium (Ref. 13).

Hypocalcemia with subsequent low

levels of ionized calcium may result in

neuromuscular irritability, heart block,

and cardiovascular failure (Ref. 13).

Therefore, the agency has determined

that the warnings in the professional

labeling for oral and rectal sodium

phosphates products in proposed

§ 334.80(b)(2) (redesignated as

§ 334.80(b)(2)(i) in this proposal) should

be expanded. The agency has made an

effort to present the warning

information in a new format using

specific headings to make it clearer and

more readable as follows:

‘‘Do not use’’ (these three words in bold

print) ‘‘in patients with congestive heart

failure.’’

‘‘Use with caution’’ (these three words in

bold print) ‘‘in patients with impaired renal

function, heart disease, acute myocardial

infarction, unstable angina, preexisting

electrolyte disturbances (such as dehydration

or those secondary to the use of diuretics),

the elderly, or people taking drugs that may

affect electrolyte levels.’’

The agency is also including the

following information regarding

prevention and treatment of an

electrolyte imbalance.

‘‘Monitor electrolytes.’’ (these two words in

bold print) ‘‘Give sufficient fluid replacement

with all oral and rectal sodium phosphates

products to prevent dehydration.’’ ‘‘What can

occur:’’ (these three words in bold print)

‘‘Hypocalcemia, hyperphosphatemia,

hypernatremia, hypokalemia, and acidosis.

These conditions are more likely to occur

when more than one dose of sodium

phosphates is given in a 24-hour period.’’

‘‘What you should do:’’ (these four words

in bold print) ‘‘Advise people to follow

recommended dose. Treatment of electrolyte

imbalance may require immediate medical

intervention with appropriate electrolyte and

fluid replacement. (Some examples of

references for treatment of this condition are

Fonkalsrud, E., and J. Keen, Hypernatremic

Dehydration Hypertonic Enemas in

Congenital Megacolon, The Journal of the

American Medical Association, 199:584586,

1967, and Edmondson, S., and T. D.

Almquist, Iatrogenic Hypocalcemic Tetany,

Annals of Emergency Medicine, 19:938–940,

1990.)’’

The agency is including additional

warnings for rectal sodium phosphates

products because of reports of its misuse

in certain individuals by health

professionals. Fatal or life-threatening

consequences have resulted from excess

dosages of sodium phosphates enemas

in adults (Refs. 4, 6, and 14) and in

young children (Refs. 10, 15, and 16).

The agency notes that many of these

adverse effects occurred when sodium

phosphates enemas were used in

children under 2 years of age. Sodium

phosphates enemas have also been

misused in individuals with colon

abnormalities (Refs. 1, 4, 10, 17, and 18)

and rectal abnormalities (Refs. 5, 19,

and 20). Individuals with a functional

abnormality of the colon, e.g., a

colostomy (Refs. 10, 21, and 22),

imperforate anus (Refs. 4 and 21), atonic

colon (Ref. 4), or congenital megacolon

(Refs. 1, 4, 10, and 21) are at risk for

hyperosmotic dehydration and

hyperphosphatemia with the use of

sodium phosphates enemas. Such

individuals have a tendency to retain

the enema for a prolonged period of

time, and considerable absorption of the

phosphate ion occurs. Several cases of

rectal gangrene have occurred after an

enema nozzle injury in individuals with

hemorrhoids (Refs. 19, 20, and 23). The

authors believed that the rectal injury

was compounded due to the necrotizing

effect of the sodium phosphates on the

rectal tissue. Other reports (Refs. 19, 20,

and 23 through 26) indicate that

following an enema tip injury to the

rectum, the presence of sodium

phosphates causes a pronounced

inflammatory response and tissue

damage which, if untreated, can

produce serious consequences. Based on

the above, the agency is proposing to

add the following warnings in the

professional labeling in proposed

§ 334.80(b)(2)(ii) for sodium phosphates

enemas to inform health professionals to

carefully monitor use in certain

individuals or not to use at all. This

information is also presented in the new

format using specific headings:

‘‘Do not use’’ (these three words in bold

print) ‘‘sodium phosphates enema in

children under 2 years of age or in patients

with congenital megacolon or imperforate

anus because of the risk of hyperosmotic

dehydration and hyperphosphatemia.’’

‘‘Stop using’’ (these two words in bold

print) ‘‘if there is resistance to the enema tip.

Forcing the tip into the rectum can result in

a serious injury that requires immediate

medical attention.’’

‘‘Use sodium phosphates enema with

extreme caution’’ (these seven words in bold

print) ‘‘in patients with a colostomy or atonic

colon (because of the risk of hyperosmotic

dehydration and hyperphosphatemia) or with

a rectal abnormality, such as hemorrhoids

(because sodium phosphates can cause

serious damage to the rectal mucosa if an

enema tip injury occurs). Using more than

one sodium phosphates enema in a 24-hour

period can cause serious electrolyte

problems.’’

The ‘‘Do not use’’ warning for sodium

phosphates enemas in

§ 334.80(b)(2)(ii)(A) may be combined

with the ‘‘Do not use’’ warning for all

sodium phosphates products in

§ 334.80(b)(2)(i)(A). The warning

proposed for sodium phosphates

products in § 334.80(b)(2) of the

tentative final monograph, which stated

‘‘Do not use in patients with megacolon,

as hypernatremic dehydration may

occur. Use with caution in patients with

impaired renal function,’’ is superseded

by the warnings in this amendment.

The agency notes that the comment

stated that a summarized version of the

professional labeling will appear on the

product’s retail package. Professional

labeling is labeling provided to health

professionals but not to the general

public. Therefore, a summarized version

of this professional labeling should not

appear on the retail package. As

discussed in section II.C of this

document, the agency has developed

labeling for sodium phosphates

products that it believes adequately
Federal Register / Vol. 63, No. 98 /Thursday, May 21, 1998 / Proposed Rules 27889

informs consumers of the proper use of

these products.

C. OTC Labeling

In § 334.58(c)(2)(i) of the tentative

final monograph (50 FR 2124 at 2155),

the agency proposed the following

warning for products containing sodium

phosphates: ‘‘Do not use this product if

you have kidney disease, unless

directed by a doctor.’’ The agency is

proposing to expand the warning for

oral and rectal products that contain

sodium phosphates because consumers

who have kidney disease (Refs. 4

through 7), heart problems (Refs. 8

through 12), or are dehydrated (Refs. 1

and 9) should not use sodium

phosphates products, unless directed by

a doctor.

The agency has also determined that

a new warning is needed to restrict the

number of days that all oral and rectal

sodium phosphates products can be

used, unless directed by a doctor. The

Panel in its report (40 FR 12902 at

12941) and the agency in the tentative

final monograph (50 FR 2124 at 2153)

recommended that the use of sodium

phosphates be restricted to 1 week (7

days). However, the agency has

reviewed new data indicating that

sodium phosphates can cause

electrolyte imbalances within 24 hours

after the initial dose is taken (Refs. 4, 11,

and 12) (also see the final rule for oral

and rectal OTC sodium phosphates drug

products published elsewhere in this

issue of the Federal Register). These

blood level changes have occurred in

individuals with no underlying renal

failure or active heart disease (Refs. 11,

12, and 27). The agency is concerned

that daily use of sodium phosphates

products for 7 days may cause

significant changes in the sodium,

potassium, phosphate, chloride, and/or

calcium blood levels. In the interest of

consumer safety and to help reduce the

risk of adverse effects that can occur

from sequential doses of sodium

phosphates, the agency believes that use

of sodium phosphates should be limited

to 3 days instead of 7 days. The revised

warning for oral and rectal sodium

phosphates, which appears in proposed

§ 334.58(c)(2)(i), states: ‘‘Do not use if’’

(these four words in bold print) ‘‘you

have kidney disease, heart problems, or

are dehydrated, or for more than 3 days,

without asking a doctor.’’

In § 334.58(c)(2)(ii) of the tentative

final monograph (50 FR 2124 at 2155),

the agency proposed the following

warning for oral dosage forms of sodium

phosphates identified in § 334.16(d), (e),

or (f): ‘‘Do not give to children under 5

years of age unless directed by a

doctor.’’ However, the agency is

proposing to revise the directions for

oral sodium phosphates products in

new § 201.307(b)(3)(ii) (21 CFR

201.307(b)(3)(ii)) (designated as

§ 334.58(d)(5)(i) in this proposal) and in

proposed § 334.58(d)(6) and (d)(7) to be

consistent with other oral OTC laxative

drug products. (See section II.D of this

document.) Therefore, for consistency,

the proposed warning in

§ 334.58(c)(2)(ii) for oral sodium

phosphates is revised to state: ‘‘Do not

give to children under 6 years of age,

without asking a doctor.’’

In § 334.58(c)(2)(iii) of the tentative

final monograph (50 FR 2124 at 2155),

the agency proposed the following

warning for sodium phosphates enemas:

‘‘Do not give to children under 2 years

of age unless directed by a doctor.’’ The

agency also proposed the following

direction for sodium phosphates enemas

in § 334.58(d)(5)(ii) (50 FR 2124 at

2155): ‘‘* * * Children under 2 years of

age: consult a doctor.’’ However,

because of adverse effects that have

occurred when sodium phosphates

enemas were used in children under 2

years of age, the agency is revising the

warning and direction statements.

Therefore, in § 334.58(c)(2)(iii) of this

proposal, the revised warning for

sodium phosphates rectal products

states: ‘‘Do not use in children under 2

years of age.’’ The corresponding

direction, which appears in

§ 334.58(d)(5)(ii)(A) in this proposal, is

revised to state: ‘‘* * * Do not use in

children under 2 years of age.’’ The

agency believes it is necessary to have

this information in both the warning

and direction sections of the labeling

because of the adverse effects that can

occur when sodium phosphates enemas

are used in children under 2 years of

age.

D. Directions

Effectiveness is not increased when a

sodium phosphates enema is retained

more than 5 minutes (Refs. 28, 29, and

30). Data indicate that a sodium

phosphates enema is usually expelled

from the rectum within 20 minutes

(Refs. 28, 29, and 30) and that increased

blood levels of phosphorus and sodium

and decreased levels of calcium can

occur within several hours (Refs. 13, 17,

and 30) if the enema is retained.

Therefore, the agency is proposing a

new direction for sodium phosphates

rectal products in § 334.58(d)(5)(ii)(B) in

this proposal, which states: ‘‘If no urge

is felt after 5 minutes of using, try to

empty bowel. Call a doctor promptly if

no liquid comes out of the rectum after

30 minutes because dehydration could

occur.’’

The agency is proposing a new

direction in § 334.58(d)(5)(ii)(C) for

sodium phosphates rectal products. A

sodium phosphates enema can cause

serious damage to the rectal mucosa if

the enema tip causes a rectal injury

(Refs. 19, 20, and 23). If the enema tip

perforates the rectum, antibiotic

treatment or a temporary colostomy may

be needed to prevent sepsis (Refs. 23

through 26, and 31). All rectal bleeding

resulting from an enema tip injury

should be medically evaluated because

rectal perforations can be painless (Refs.

20, 25, and 31). Therefore, the new

direction states: ‘‘Stop using if tip is

hard to insert. Forcing the tip into the

rectum can cause injury (especially if

you have hemorrhoids). If enema tip

causes rectal bleeding or pain, get

immediate medical care.’’

The agency is aware that labeling that

was submitted to the Panel (Ref. 32) and

currently marketed labeling (Ref. 33) for

oral sodium phosphates products

contain dosages for children 5 to 9 years

of age, and for children 10 and 11 years

of age. The Panel in its report (40 FR

12902 at 12940) and the agency in the

tentative final monograph (50 FR 2124

at 2155) recommended dosages of oral

sodium phosphates products for these

age groups. Elsewhere, in this issue of

the Federal Register, the agency

included the above age ranges in the

directions in new § 201.307(b)(3)(ii).

The agency notes that the directions for

sodium phosphates oral solution

contain separate dosages for children 10

and 11 years of age, and for children 5

to 9 years of age. These age ranges are

not consistent with age ranges used for

the majority of OTC laxative drug

products, which recommend dosages for

children 6 to 11 years of age.

Therefore, the agency is proposing to

revise the directions for oral sodium

phosphates products in new

§ 201.307(b)(3)(ii) (designated as

§ 334.58(d)(5)(i) in this proposal), and in

proposed § 334.58(d)(6) and (d)(7) to be

consistent with other oral OTC laxative

drug products. The proposed directions

in § 334.58(d)(5)(i) state:

* * * Children 6 to 9 years of age: Oral

dosage is dibasic sodium phosphate 0.86 to

1.89 g and monobasic sodium phosphate 2.2

to 5.05 g (5 to 10 mL dibasic sodium

phosphate/monobasic sodium phosphate oral

solution) as a single daily dose. ‘Do not take

more than 10 mL (2 teaspoonfuls) in a 24-

hour period.’ Children under 6 years of age:

ask a doctor.

The proposed directions in

§ 334.58(d)(6) for products containing

dibasic sodium phosphate identified in

§ 334.16(e) state: ‘‘* * * Children 6 to 9

years of age: Oral dosage is 0.86 to 1.89

g in a single daily dose. Children under

6 years of age: ask a doctor.’’ The
27890 Federal Register / Vol. 63, No. 98 /Thursday, May 21, 1998 / Proposed Rules

proposed directions in § 334.58(d)(7) for

products containing monobasic sodium

phosphate identified in § 334.16(f) state:

‘‘* * * Children 6 to 9 years of age: Oral

dosage is 1.12 to 5.05 g in a single daily

dose. Children under 6 years of age: ask

a doctor.’’

E. Time to Effect

The agency is proposing to revise the

time to effect statement in proposed

§ 334.58(b)(2) for sodium phosphates

rectal products from 2 to 15 minutes to

1 to 5 minutes. In three studies (Refs.

28, 29, and 30), 98 subjects (280

observations) were evaluated to

determine the time to effect following

use of sodium phosphates enema. In 98

percent of the observations (33 subjects

accounted for 261/280 observations), the

reported time to effect was within 10

minutes. In 83 percent of the

observations, the time to effect was

between 1 and 5 minutes. The average

time to effect was 4 to 5 minutes and the

mode was 3 to 5 minutes. The data do

not indicate that sodium phosphates is

more effective if the solution is retained

more than 5 minutes (Refs. 28, 29, and

30). Therefore, the agency is proposing

to revise § 334.58(b)(2) to state: ‘‘This

product generally produces bowel

movement in 1 to 5 minutes.’’

The agency invites specific comments

on these proposed labeling statements.

The agency will discuss its decision on

these labeling proposals in a future

issue of the Federal Register. Until the

agency makes a final determination on

these labeling statements, the agency

encourages all manufacturers of sodium

phosphates products voluntarily to label

their products to include the proposed

labeling statements. Because FDA is

encouraging that the proposed labeling

statements be used on a voluntary basis

at this time, the agency will give

manufacturers ample time after

publication of a final rule to use up any

labeling implemented in conformance

with this document.

III. References

The following references have been

placed on display in the Dockets

Management Branch (address above)

and may be seen by interested persons

between 9 a.m. and 4 p.m., Monday

through Friday.

1. Fonkalsrud, E., and J. Keen,

‘‘Hypernatremic Dehydration Hypertonic

Enemas in Congenital Megacolon,’’ The

Journal of the American Medical Association,

199:584–586, 1967.

2. Goodman, L., and A. Gilman, The

Pharmacological Basis of Thearpeutics, 6th

ed., McGraw Hill, New York, p. 1005, 1980.

3. McConnell, T. H., ‘‘Fatal Hypocalcemia

from Phosphate Absorption from Laxative

Preparation,’’ The Journal of the American

Medical Association, 216:147–148, 1971.

4. Korzets, A. et al., ‘‘Life-Threatening

Hyperphosphatemia and Hypocalcemic

Tetany Following the Use of Fleet Enemas,’’

Journal of the American Geriatric Society,

40:620–621, 1992.

5. Grosskopf, I. et al.,

‘‘Hyperphosphataemia and Hypocalcaemia

Induced by Hypertonic Phosphate Enema—

An Experimental Study and Review of the

Literature,’’ Human and Experimental

Toxicology, 10:351–355, 1991.

6. Biberstein, M., and B. A. Parker,

‘‘Enema-Induced Hyperphosphatemia,’’ The

American Journal of Medicine, 79:645–646,

1985.

7. Oxnard, S. C., J. O’Bell, and W. E. Grupe,

‘‘Severe Tetany in an Azotemic Child Related

to a Sodium Phosphate Enema,’’ Pediatrics,

53:105–106, 1974.

8. Wiberg, J. J., G. G. Turner, and F. Q.

Nuttall, ‘‘Effect of Phosphate or Magnesium

Cathartics on Serum Calcium,’’ Archives of

Internal Medicine, 138:1114–1116, 1978.

9. Gilman, A. et al., The Pharmacological

Basis of Therapeutics, 8th ed., Pergamon

Press, New York, p. 919, 1992.

10. Martin, R. R. et al., ‘‘Fatal Poisoning

from Sodium Phosphate Enema—Case Report

and Experimental Study,’’ The Journal of the

American Medical Association, 257:2190–

2192, 1987.

11. Vanner, S. J. et al., ‘‘A Randomized

Prospective Trial Comparing Oral Sodium

Phosphate with Standard Polyethylene

Glycol-Based Lavage Solution (GoLytely) in

the Preparation of Patients for Colonoscopy,’’

The American Journal of Gastroenterology,

85:422–427, 1990.

12. Kolts, B. E. et al., ‘‘A Comparison of the

Effectiveness and Patient Tolerance of Oral

Sodium Phosphate, Castor Oil, and Standard

Electrolyte Lavage for Colonoscopy or

Sigmoidoscopy Preparation,’’ The American

Journal of Gastroenterology, 88:1218–1223,

1993.

13. Cagir, B. et al., ‘‘Hypocalcemia in

Surgical Critical Care Patients: Measurements

of Ionized Calcium,’’ Contemporary Surgery,

45:71–78, 1994.

14. Rohack, J. J., B. R. Mehta, and K.

Subramanyam, ‘‘Hyperphosphatemia and

Hypocalcemic Coma Associated with

Phosphate Enema,’’ Southern Medical

Journal, 78:1241–1242, 1985.

15. Edmondson, S., and T. D. Almquist,

‘‘Iatrogenic Hypocalcemic Tetany,’’ Annals of

Emergency Medicine, 19:938–940, 1990.

16. Sotos, J. F. et al., ‘‘Hypocalcemic Coma

Following Two Pediatric Phosphate

Enemas,’’ Pediatrics, 60:305–307, 1977.

17. Spinrad, S. et al., ‘‘Treating

Constipation with Phosphate Enema: An

Unnecessary Risk,’’ Israel Journal of Medical

Sciences, 25:237–238, 1989.

18. Schuchmann, G. D., and P. J. Barcia,

‘‘Phosphate Absorption from Fleet Enemas in

Adults,’’ Current Surgery, 46:120–122, 1989.

19. Sweeney, J. L. et al., ‘‘Rectal Gangrene:

A Complication of Phosphate Enema,’’

Medical Journal of Australia, 144:374–375,

1986.

20. Saltzstein, R. J., E. Quebbeman, and J.

L. Melvin, ‘‘Anorectal Injuries Incident to

Enema Administration. A Recurring

Avoidable Problem,’’ American Journal of

Physical Medical and Rehabilitation, 67:186–

188, 1988.

21. Honig, P. J., and P. G. Holtzapple,

‘‘Hypocalcemic Tetany Following Hypertonic

Phosphate Enemas,’’ Clinical Pediatrics,

14:678–679, 1975.

22. Hunter, F. M. et al.,

‘‘Hyperphosphataemia after Enemas in

Childhood: Prevention and Treatment,’’

Archives of Diseases in Childhood, 68:233–

234, 1993.

23. Turell, R., ‘‘Laceration to Anorectum

Incident to Enema,’’ Archives of Surgery,

81:953–954, 1960.

24. Bell, A. M., ‘‘Colonic Perforation with

a Phosphate Enema,’’ Journal of the Royal

Society of Medicine, 83:54–55, 1990.

25. Peitsch, J. B., H. M. Shizgal, and J. L.

Meakins, ‘‘Injury by Hypertonic Phosphate

Enema,’’ Canadian Medical Association

Journal, 116:1169–1170, 1977.

26. Hool, G. J., E. L. Bokey, and M. T.

Pheils, ‘‘Enema-Nozzle Injury of the

Rectum,’’ The Medical Journal of Australia,

1:364 and 381, 1980.

27. Clarkston, W. K. et al., ‘‘A Single Blind

Comparison of Serum Electrolytes, Serum

Phosphorus, Serum Calcium, and Ventricular

Arrhythmias in Outpatients Receiving

Nulytely Versus Fleet Phospho-Soda

Preparation for Colonoscopy: Preliminary

Results’’ (unpublished study), pp. 1928,

1994, OTC Vol. 090TFM4, Docket No. 78N–

036L, Dockets Management Branch.

28. Page, S. G., C. R. Riley, and H. B. Haag,

‘‘A Comparative Clinical Study of Several

Enemas,’’ The Journal of the American

Medical Association, 157:1208–1210, 1955.

29. Stempien, S. J., ‘‘Double-Blind

Evaluation of Sorbitol, Phosphate, and

Dextrose Enemas at Sigmoidoscopy,’’

Gastroenterology, 36:830–831, 1959.

30. Bodi, T., and G. H. Frey, ‘‘Clinical

Evaluations of Small-Volume Enemas,’’

Pennsylvania Medical Journal, 68:35–38,

1965.

31. Weiss, Y., P. Grunberger, and S.

Aronowitz, ‘‘Asymptomatic Rectal

Perforation with Retroperitoneal

Emphysema,’’ American Society of Colon

and Rectal Surgeons, 24:545–547, 1980.

32. OTC Vol. 090011.

33. Labeling for Fleet Phospho-Soda, in

OTC Vol. 090TFM3, Docket No. 78N–036L,

Dockets Management Branch.

IV. Summary of the Agency’s Proposal

for OTC Laxative Drug Products

Containing Sodium Phosphates

Based on new information, the agency

is proposing changes in the labeling for

oral and rectal sodium phosphates drug

products. A summary of the changes

proposed in this document follows.

1. The agency is revising proposed

§ 334.16(d), (e), and (f) of the

monograph to use the current USP

names for dibasic sodium phosphate/

monobasic sodium phosphate (sodium

phosphates) drug products. (See section

I of this document.)

2. The agency is revising the warning

proposed in § 334.58(c)(2)(ii) for
Federal Register / Vol. 63, No. 98 /Thursday, May 21, 1998 / Proposed Rules 27891

products containing oral sodium

phosphates identified in § 334.16(d), (e),

and (f) to state: ‘‘Do not give to children

under 6 years of age, without asking a

doctor.’’(See section II.C of this

document.)

3. The agency is revising the

directions for oral sodium phosphates in

new § 201.307(b)(3)(ii) (designated as

§ 334.58(d)(5)(i) in this proposal) and in

proposed § 334.58(d)(6) and (d)(7) to be

consistent with other oral OTC laxative

drug products. The directions will

include oral dosages for children 6 years

of age and older and state to ask a doctor

for children under 6 years of age. (See

section II.D of this document.)

4. The agency is changing the ‘‘time

to effect’’ statement proposed in

§ 334.58(b)(2) for rectal dosage forms of

sodium phosphates from 2 to 15

minutes to 1 to 5 minutes. (See section

II.E of this document.)

5. The agency is expanding the

warning for oral and rectal sodium

phosphates proposed in § 334.58(c)(2)(i)

to state: ‘‘Do not use if’’ (these four

words in bold print) ‘‘you have kidney

disease, heart problems, or are

dehydrated, or for more than 3 days,

without asking a doctor.’’ (See section

II.C of this document.)

6. The agency is revising the warning

proposed for rectal dosage forms of

sodium phosphates in § 334.58(c)(2)(iii)

which stated, ‘‘Do not give to children

under 2 years of age unless directed by

a doctor,’’ to read: ‘‘Do not use in

children under 2 years of age.’’ The

agency is also revising the direction

proposed for rectal sodium phosphates

in § 334.58(d)(5)(ii) which stated,

‘‘Children under 2 years of age: consult

a doctor,’’ with a new direction in

§ 334.58(d)(5)(ii)(A) that states: ‘‘Do not

use in children under 2 years of age.’’

(See section II.C of this document.)

7. The agency is proposing new

directions for rectal dosage forms of

sodium phosphates in

§ 334.58(d)(5)(ii)(B) that state: ‘‘If no

urge is felt after 5 minutes of using, try

to empty bowel. Call a doctor promptly

if no liquid comes out of the rectum

after 30 minutes because dehydration

could occur.’’ (See section II.D of this

document.)

8. The agency is proposing new

directions in § 334.58(d)(5)(ii)(C) for

rectal dosage forms of sodium

phosphates that state: ‘‘Stop using if tip

is hard to insert. Forcing the tip into the

rectum can cause injury (especially if

you have hemorrhoids). If enema tip

causes rectal bleeding or pain, get

immediate medical care.’’ (See section

II.D of this document.)

9. The agency is revising the

professional labeling for oral and rectal

sodium phosphates proposed in

§ 334.80(b)(2) to include additional ‘‘Do

not use’’ and ‘‘Use with caution’’

warnings. The agency is also including

new information about monitoring

electrolytes and treating electrolyte

imbalances. The new warnings and

other information appear in

§ 334.80(b)(2)(i) and (b)(2)(ii). (See

section II.B of this document.)

10. The agency has made an effort to

shorten and simplify some of the

labeling, e.g., by using the phrase

‘‘without asking a doctor’’ instead of

‘‘unless directed by a doctor.’’ The

agency has also proposed a new format

for professional labeling. The agency

believes that these changes will provide

a clear and readable format for these

labeling statements. FDA is inviting

specific comments on this labeling

format and on the wording of these

statements.

V. Analysis of Impacts

FDA has examined the impacts of the

proposed rule under Executive Order

12866 and the Regulatory Flexibility Act

(5 U.S.C. 601–612). Executive Order

12866 directs agencies to assess all costs

and benefits of available regulatory

alternatives and, when regulation is

necessary, to select regulatory

approaches that maximize net benefits

(including potential economic,

environmental, public health and safety,

and other advantages; distributive

impacts; and equity). Under the

Regulatory Flexibility Act, if a rule has

a significant economic impact on a

substantial number of small entities, an

agency must analyze regulatory options

that would minimize any significant

impact of the rule on small entities.

Title II of the Unfunded Mandates

Reform Act (2 U.S.C. 1501 et seq.)

requires that agencies prepare a written

statement and economic analysis before

proposing any rule that may result in an

expenditure in any 1 year by State,

local, and tribal governments, in the

aggregate, or by the private sector, of

$100 million (adjusted annually for

inflation).

The agency believes that this

proposed rule is consistent with the

principles set out in the Executive Order

and in these two statutes. The purpose

of this proposed rule is to add warning

and direction statements to the general

OTC and health professional (for health

professionals only) labeling of oral and

rectal OTC sodium phosphates drug

products. These warning and direction

statements concern product toxicity and

are intended to help ensure the safe and

effective use of all OTC sodium

phosphates drug products. Potential

benefits include reduced toxicity when

consumers use, and health professionals

recommend, these products.

The agency has been informed that

relabeling costs of the type required by

this proposed rule (changes to both

consumer and professional labeling)

generally average about $3,000 to $4,000

per stock keeping unit (SKU)

(individual products, packages, and

sizes). The agency is aware of 3

manufacturers that together produce 4

SKU’s of oral sodium phosphates drug

products and approximately 125 SKU’s

of rectal sodium phosphates drug

products. There may be a few additional

small manufacturers or a few additional

products in the marketplace that are not

identified in the sources FDA reviewed.

Assuming that there are about 130

affected OTC SKU’s in the marketplace,

total one-time costs of relabeling would

be $390,000 to $520,000.

The agency also believes that actual

costs could be lower for several reasons.

First, most of the label changes will be

made by private label manufacturers

that tend to use simpler and less

expensive labeling. Second, labeling

changes would not be required until the

final monograph for OTC laxative drug

products is issued and becomes

effective. The agency is proposing a 12-

month implementation period that

would allow the manufacturers to

coordinate these changes with routinely

scheduled label printing and/or other

revisions required by the final

monograph for OTC laxative drug

products. Thus, relabeling costs for

these products would be mitigated or

reduced by the cost of other labeling

changes that the final monograph will

also require.

The proposed rule would not require

any new reporting and recordkeeping

activities. Therefore, no additional

professional skills are needed. There are

no other Federal rules that duplicate,

overlap, or conflict with the proposed

rule.

The agency considered but rejected

several labeling alternatives: (1)

Voluntary relabeling, (2) publication of

the labeling information in the FDA

Drug Bulletin or professional journals,

and (3) an exemption from coverage for

small entities. The agency does not

consider the first or third alternative

acceptable because they do not assure

that consumers or health professionals

will have the most recent needed

information for safe and effective use of

these sodium phosphates drug products.

The agency considers the second

alternative useful and may proceed with

such publications. However, such

publications do not provide a

permanent labeling requirement, which
27892 Federal Register / Vol. 63, No. 98 /Thursday, May 21, 1998 / Proposed Rules

the agency considers necessary for these

products.

This proposed rule may have a

significant economic impact on the

manufacturers of these products, all of

which are considered to be small

entities, using the U.S. Small Business

Administration designations for this

industry (750 employees). The agency

believes that any other unidentified

manufacturer of these products is also

likely to be a small entity. These

manufacturers will need to change the

information panel of each affected

sodium phosphates SKU and print new

professional labeling. Among the steps

the agency is taking to minimize the

impact on these small entities are: (1) To

provide 1 year for implementation to

enable entities to use up existing

labeling stock, and (2) to allow these

labeling changes to be coordinated with

other labeling changes required by the

final monograph. The agency believes

that these actions should help reduce

the relabeling cost for small entities.

The agency considered but rejected

both a shorter and a longer

implementation period. While the

agency would like to have this new

labeling in place as soon as possible, it

considers a period less than 1 year

difficult for manufacturers to implement

all of the labeling required by the final

monograph. The agency considered a

longer effective date but finds it

unacceptable because it would not

assure that consumers have the most

recent needed information for safe and

effective use of OTC sodium phosphates

drug products at the earliest possible

time. Manufacturers are encouraged to

implement the new labeling as soon as

possible after the final monograph is

published.

The analysis shows that this proposed

rule is not economically significant

under Executive Order 12866 and that

the agency has undertaken important

steps to reduce the burden to small

entities. Nevertheless, some entities,

especially those private label

manufacturers that provide labeling for

a number of the affected products, may

incur significant impacts. Thus, this

economic analysis, together with other

relevant sections of this document,

serves as the agency’s initial regulatory

flexibility analysis, as required under

the Regulatory Flexibility Act. Finally,

this analysis shows that the Unfunded

Mandates Act does not apply to the

proposed rule because it would not

result in an expenditure in any 1 year

by State, local, and tribal governments,

in the aggregate, or by the private sector,

of $100 million.

The agency invites public comment

regarding any substantial or significant

economic impact that this rulemaking

would have on OTC laxative drug

products containing sodium

phosphates. Comments regarding the

impact of this rulemaking on OTC

laxative drug products containing

sodium phosphates should be

accompanied by appropriate

documentation. The agency is providing

a period of 90 days from the date of

publication of this proposed rulemaking

in the Federal Register for development

and submission of comments on this

subject. 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.

VI. 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 labeling statements are a

‘‘public disclosure of information

originally supplied by the Federal

government to the recipient for the

purpose of disclosure to the public’’ (5

CFR 1320.3(c)(2)).

VII. Environmental Impact

The agency has determined under 21

CFR 25.31(c) that this action is of a type

that does not individually or

cumulatively have a significant effect on

the human environment. Therefore,

neither an environmental assessment

nor an environmental impact statement

is required.

VIII. Request for Comments

Interested persons may, on or before

August 19, 1998, submit written

comments or objections on the proposed

regulation to the Dockets Management

Branch (address above). Three copies of

all comments or objections are to be

submitted, except that individuals may

submit one copy. Comments should 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 and objections may

be seen in the office above between 9

a.m. and 4 p.m., Monday through

Friday.

FDA is proposing that any final rule

based on this proposal be effective 12

months after the date of its publication

in the Federal Register.

List of Subjects in 21 CFR Part 334

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, it is proposed that

21 CFR part 334 (proposed in the

Federal Register of January 15, 1985, 50

FR 2124) be amended as follows:

PART 334—LAXATIVE DRUG

PRODUCTS FOR OVER-THECOUNTER HUMAN USE

1. The authority citation for 21 CFR

part 334 continues to read as follows:

Authority: 21 U.S.C. 321, 351, 352, 353,

355, 360, 371.

2. Section 334.16 is amended by

revising paragraphs (d), (e), and (f) to

read as follows:

§ 334.16 Saline laxative active ingredients.

* * * * *

(d) Dibasic sodium phosphate/

monobasic sodium phosphatemarketed

as a solution.

(e) Dibasic sodium phosphate.

(f) Monobasic sodium phosphate.

3. Section 334.58 is amended by

revising paragraph (b)(2), by revising

paragraph (c)(2), by revising the heading

of paragraph (d)(5) and text of paragraph

(d)(5)(i), by redesignating paragraph

(d)(5)(ii) as (d)(5)(ii)(A) and revising

new (d)(5)(ii)(A), by adding new

paragraphs (d)(5)(ii)(B) and (d)(5)(ii)(C),

and by revising the headings and text of

paragraphs (d)(6) and (d)(7) to read as

follows:

§ 334.58 Labeling of saline laxative drug

products.

* * * * *

(b) * * *

(2) Rectal dosage forms. ‘‘This

product generally produces bowel

movement in 1 to 5 minutes.’’

(c) * * *

(2) For products containing dibasic

sodium phosphate or monobasic

sodium phosphate identified in

§ 334.16(d), (e), or (f)—(i) ‘‘Do not use

if’’ (these four words in bold print) ‘‘you

have kidney disease, heart problems, or

are dehydrated, or for more than 3 days,

without asking a doctor.’’

(ii) Oral dosage forms. ‘‘Do not give to

children 5 years of age and under,

without asking a doctor.’’

(iii) Rectal dosage forms. ‘‘Do not use

in children under 2 years of age.’’

(d) * * *

(5) For products containing dibasic

sodium phosphate/ monobasic sodium

phosphate identified in § 334.16(d) and

marketed as a solution—(i) Oral dosage.

Adults and children 12 years of age and

over: Oral dosage is dibasic sodium

phosphate 3.42 to 7.56 grams and

monobasic sodium phosphate 9.1 to

20.2 grams (20 to 45 milliliters (mL)
Federal Register / Vol. 63, No. 98 /Thursday, May 21, 1998 / Proposed Rules 27893

dibasic sodium phosphate/monobasic

sodium phosphate oral solution) as a

single daily dose. ‘‘Do not take more

than 45 mL (9 teaspoonfuls or 3

tablespoonfuls) in a 24-hour period.’’

Children 10 and 11 years of age: Oral

dosage is dibasic sodium phosphate

1.71 to 3.78 grams and monobasic

sodium phosphate 4.5 to 10.1 grams (10

to 20 mL dibasic sodium phosphate/

monobasic sodium phosphate oral

solution) as a single daily dose. ‘‘Do not

take more than 20 mL (4 teaspoonfuls)

in a 24-hour period.’’ Children 6 to 9

years of age: Oral dosage is dibasic

sodium phosphate 0.86 to 1.89 gram and

monobasic sodium phosphate 2.2 to

5.05 grams (5 to 10 mL dibasic sodium

phosphate/monobasic sodium

phosphate oral solution) as a single

daily dose. ‘‘Do not take more than 10

mL (2 teaspoonfuls) in a 24-hour

period.’’ Children under 6 years of age:

ask a doctor.

(ii) Rectal enema dosage. (A) Adults

and children 12 years of age and over:

Enema dosage is dibasic sodium

phosphate 6.84 to 7.56 grams and

monobasic sodium phosphate 18.24 to

20.16 grams in a single daily dose.

Children 2 to 11 years of age: Enema

dosage is dibasic sodium phosphate

3.42 to 3.78 grams and monobasic

sodium phosphate 9.12 to 10.08 grams

in a single daily dose. ‘‘Do not use in

children under 2 years of age.’’

(Manufacturers should convert these

dosages to the amount of solution to be

used.)

(B) ‘‘If no urge is felt after 5 minutes

of using, try to empty bowel. Call a

doctor promptly if no liquid comes out

of the rectum after 30 minutes because

dehydration could occur.’’

(C) ‘‘Stop using if tip is hard to insert.

Forcing the tip into the rectum can

cause injury (especially if you have

hemorrhoids). If enema tip causes rectal

bleeding or pain, get immediate medical

care.’’

(6) For products containing dibasic

sodium phosphate identified in

§ 334.16(e). Adults and children 12

years of age and over: Oral dosage is

3.42 to 7.56 grams in a single daily dose.

Children 10 to 11 years of age: Oral

dosage is 1.71 to 3.78 grams in a single

daily dose. Children 6 to 9 years of age:

Oral dosage is 0.86 to 1.89 gram in a

single daily dose. Children under 6

years of age: ask a doctor.

(7) For products containing

monobasic sodium phosphate identified

in § 334.16(f). Adults and children 12

years of age and over: Oral dosage is 4.5

to 20.2 grams in a single daily dose.

Children 10 to 11 years of ages: Oral

dosage is 2.25 to 10.1 grams in a single

daily dose. Children 6 to 9 years of age:

Oral dosage is 1.12 to 5.05 grams in a

single daily dose. Children under 6

years of age: ask a doctor.

4. Section 334.80 is amended by

redesignating paragraph (b)(2) as

paragraph (b)(2)(i) and revising it, and

by adding paragraph (b)(2)(ii), to read as

follows.

§ 334.80 Professional labeling.

* * * * *

(b) * * *

(2) For products containing dibasic

sodium phosphate or monobasic

sodium phosphate identified in

§ 334.16(d), (e), or (f)—(i) Oral and

rectal dosage forms—(A) ‘‘Do not use’’

(these three words in bold print) ‘‘in

patients with congestive heart failure.’’

(B) ‘‘Use with caution’’ (these three

words in bold print) ‘‘in patients with

impaired renal function, heart disease,

acute myocardial infarction, unstable

angina, preexisting electrolyte

disturbances (such as dehydration or

those secondary to the use of diuretics),

the elderly, or people taking drugs that

may affect electrolyte levels.’’

(C) ‘‘Monitor electrolytes.’’ (these two

words in bold print) ‘‘Give sufficient

fluid replacement with all oral and

rectal sodium phosphates products to

prevent dehydration.’’

(D) ‘‘What can occur:’’ (these three

words in bold print) ‘‘Hypocalcemia,

hyperphosphatemia, hypernatremia,

hypokalemia, and acidosis. These

conditions are more likely to occur

when more than one dose of sodium

phosphates is given in a 24-hour

period.’’

(E) ‘‘What you should do:’’ (these four

words in bold print) ‘‘Advise people to

follow recommended dose. Treatment of

electrolyte imbalance may require

immediate medical intervention with

appropriate electrolyte and fluid

replacement. (Some examples of

references for treatment of this

condition are Fonkalsrud, E., and J.

Keen, ‘Hypernatremic Dehydration

Hypertonic Enemas in Congenital

Megacolon,’ The Journal of the

American Medical Association,

199:584–586, 1967, and Edmondson, S.,

and T. D. Almquist, ‘Iatrogenic

Hypocalcemic Tetany,’ Annals of

Emergency Medicine, 19:938–940,

1990.)’’

(ii) Rectal dosage forms. (A) ‘‘Do not

use’’ (these three words in bold print)

‘‘sodium phosphates enema in children

under 2 years of age or in patients with

congenital megacolon or imperforate

anus because of the risk of hyperosmotic

dehydration and hyperphosphatemia.’’

(B) ‘‘Stop using’’ (these two words in

bold print) ‘‘if there is resistance to the

enema tip. Forcing the tip into the

rectum can result in a serious injury that

requires immediate medical attention.’’

(C) ‘‘Use sodium phosphates enema

with extreme caution’’ (these seven

words in bold print) ‘‘in patients with

a colostomy or atonic colon (because of

the risk of hyperosmotic dehydration

and hyperphosphatemia) or with a

rectal abnormality, such as hemorrhoids

(because sodium phosphates can cause

serious damage to the rectal mucosa if

an enema tip injury occurs). Using more

than one sodium phosphates enema in

a 24-hour period can cause serious

electrolyte problems.’’

* * * * *

Dated: April 27, 1998.

William K. Hubbard,

Associate Commissioner for Policy

Coordination.

[FR Doc. 98–12054 Filed 5–20–98; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF TRANSPORTATION

Coast Guard

33 CFR Part 165

[CGDO1–98–002]

RIN 2121–AA97

Safety Zone; New York Super Boat

Race, New York

AGENCY: Coast Guard, DOT.

ACTION: Notice of proposed rulemaking.

SUMMARY: The Coast Guard proposes to

establish a temporary safety zone in the

lower Hudson River, for the New York

Super Boat Race. The temporary safety

zone would be in effect on Sunday,

September 13, 1998, from 11:30 a.m.

until 4:00 p.m. unless extended or

terminated sooner by the Captain of the

Port, New York. The proposed safety

zone would restrict vessel traffic in the

Lower Hudson River between Battery

Park and Pier 76 in Manhattan. The

proposed safety zone is needed to

protect racing participants and spectator

craft from the hazards associated with

high speed powerboat racing.

DATES: Comments must be received on

or before August 19, 1998.

ADDRESSES: Comments should be

mailed to Lieutenant Junior Grade Alma

Kenneally, Waterways Oversight

Branch, Coast Guard Activities New

York, 212 Coast Guard Drive, Staten

Island, New York 10305.

FOR FURTHER INFORMATION CONTACT:

Lieutenant Junior Grade Alma

Kenneally, Waterways Oversight

Branch, Coast Guard Activities New

York (718) 354–4195.