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

(301) 504–0800 or delivered to the allow garments sized for a child nine PART 1616ÐSTANDARD FOR THE Office of the Secretary, Room 501, 4330 months and under and tight-fitting FLAMMABILITY OF CHILDREN'S East-West Highway, Bethesda, Maryland garments in sizes above nine months to SLEEPWEAR: SIZES 7 THROUGH 14 20814. Copies should be submitted in be sold and used as sleepwear. five copies and captioned ‘‘Sleepwear Therefore, the Commission proposes to 1. The authority citation for part 1616 Policy Statement.’’ Comments may also modify the policy statements at continues to read as follows: be filed by telefacsimile to (301) 504– 1615.64(d) and 1616.65(d) to provide Authority: Sec. 4, 67 Stat. 112, as 0127 or by e-mail to cpsc [email protected]. that infant garments (defined in the amended, 81 Stat. 569–70; 15 U.S.C. 1193. FOR FURTHER INFORMATION CONTACT: amended sleepwear standard at 16 CFR 2. Section 1616.65 is amended by Patricia Fairall, Program Manager, 1615.1(c)(1) as sized for a child nine revising paragraph (d) introductory text Office of Compliance, Consumer months and under) and ‘‘tight-fitting’’ to read as follows: Product Safety Commission, garments (defined in the amended Washington, D.C. 20207; telephone sleepwear standard at 16 CFR 1615.1(o) § 1616.65 Policy scope of the standard. (301) 504–0400, extension 1369. and 1616.2(m)) can be marketed and * * * * * SUPPLEMENTARY INFORMATION: promoted with other sleepwear. (d) Retailers, distributors, and For the reasons stated above and wholesalers, as well as manufacturers, A. Background pursuant to the authority of Section 4 of importers, and other persons (such as The Consumer Product Safety the Flammable Fabrics Act (15 U.S.C. converters) introducing a fabric or Commission enforces two flammability 1193), the Commission proposes to garment into commerce which does not standards for children’s sleepwear. The amend 16 CFR 1615.64 and 1616.65 to meet the requirements of the flammability standard for children’s read as follows: flammability standards for children’s sleepwear in sizes 0 through 6X is sleepwear, have an obligation not to codified at 16 CFR Part 1615. The PART 1615ÐSTANDARD FOR THE promote or sell such fabric or garment flammability standard for children’s FLAMMABILITY OF CHILDREN'S for use as an item of children’s sleepwear in sizes 7 through 14 is SLEEPWEAR: SIZES 0 THROUGH 6X sleepwear. Also, retailers, distributors, codified at 16 CFR Part 1616. and wholesalers are advised not to On September 9, 1996, the 1. The authority citation for part 1615 advertise, promote, or sell as an item of Commission issued a final rule continues to read as follows: children’s sleepwear any item which a amending the flammability standards Authority: Sec. 4, 67 Stat. 112, as manufacturer, importer, or other person for children’s sleepwear to exclude from amended, 81 Stat. 569–70; 15 U.S.C. 1193. (such as a converter) introducing the the definition of ‘‘children’s sleepwear,’’ item into commerce has indicated by codified at 16 CFR 1615.1(a) and 2. Section 1615.64 is amended by label, invoice, or, otherwise, does not 1616.2(a), (1) garments sized for infants revising paragraph (d) introductory text meet the requirements of the children’s nine months of age or younger and (2) to read as follows: sleepwear flammability standards and is tight-fitting garments for children older not intended or suitable for use as § 1615.64 Policy to clarify scope of the sleepwear. ‘‘Tight-fitting’’ garments as than nine months. 61 FR 47634. The standard. defined by § 1616.2(m) are exempt from Commission found that such tight- * * * * * fitting garments did not present an the standard which requires flame unreasonable risk of injury. Rather, the (d) Retailers, distributors, and resistance. They may be marketed as Commission’s information showed that wholesalers, as well as manufacturers, sleepwear for purposes of this section. many severe incidents occurred with importers, and other persons (such as Additionally, retailers are advised: loose-fitting garments such as oversized converters) introducing a fabric or * * * * * t-shirts used inappropriately as garment into commerce which does not Dated: May 12, 1998. sleepwear. The Commission concluded meet the requirements of the Sadye E. Dunn, that garments fitting closely and that flammability standards for children’s Secretary, Consumer Product Safety touch the body at key points should be sleepwear, have an obligation not to Commission. exempt from the sleepwear standards promote or sell such fabric or garment [FR Doc. 98–13028 Filed 5–20–98; 8:45 am] because they do not present the same for use as an item of children’s BILLING CODE 6355±01±P risk as loose-fitting garments. These sleepwear. Also, retailers, distributors, amendments became effective on and wholesalers are advised not to January 1, 1997. However, the advertise, promote, or sell as an item of DEPARTMENT OF HEALTH AND Commission also issued a stay of children’s sleepwear any item which a HUMAN SERVICES enforcement for close-fitting garments manufacturer, importer, or other person which are labeled and promoted as (such as a converter) introducing the Food and Drug Administration underwear. That stay expires on June 9, item into commerce has indicated by 1998. label, invoice, or, otherwise, does not 21 CFR Part 334 meet the requirements of the children’s [Docket No. 78N±036L] B. Clarification sleepwear flammability standards and is The Commission has become aware not intended or suitable for use as RIN 0910±AA01 that the garment industry is concerned sleepwear. ‘‘Infant garments’’ as defined Laxative Drug Products for Over-the- about the policy statements in 16 CFR by § 1615.1(c) and ‘‘tight-fitting’’ Counter Human Use; Proposed 1615.64(d) and 1616.65(d), which garments as defined by § 1615.1(o) are Amendment to the Tentative Final suggest segregation of items covered by exempt from the standard which Monograph the children’s sleepwear standards from requires flame resistance. They may be marketed as sleepwear for purposes of all fabrics and garments that are beyond AGENCY: Food and Drug Administration, this section. Additionally, retailers are the scope of the children’s sleepwear HHS. standards. The purpose of the advised: ACTION: Notice of proposed rulemaking. September 9, 1996 final rule was to * * * * * Federal Register / Vol. 63, No. 98 / Thursday, May 21, 1998 / Proposed Rules 27887

SUMMARY: The Food and Drug published in the Federal Register of a doctor) in the monograph for OTC Administration (FDA) is amending the January 15, 1985 (50 FR 2124). The laxative drug products. However, that tentative final monograph for over-the- agency also proposed monograph status monograph has not been finalized to counter (OTC) laxative drug products to for sodium phosphates oral solution 3. date. Because of the potential serious include additional general and (See proposed § 334.58(d)(5)(i), 50 FR safety risk involved, elsewhere in this professional labeling for oral and rectal 2124 at 2152 and 2155.) In addition to issue of the Federal Register the agency dibasic sodium phosphate/monobasic its use as an OTC laxative for the relief is finalizing the package size limitation sodium phosphate (sodium phosphates) of occasional constipation, sodium and warning prior to the completion of drug products. FDA is proposing new phosphates oral solution is used as part the final monograph for OTC laxative warnings and directions for these of a bowel cleansing regimen in drug products. The agency is including products and a new time to effect preparing a patient for surgery or for this information in part 201 (21 CFR statement for rectal products based on preparing the colon for x-ray or part 201) at this time and will new data submitted after publication of endoscopic examination. (See proposed incorporate it into the final monograph the tentative final monograph for OTC § 334.80(a)(2), 50 FR 2124 at 2157.) for OTC laxative drug products at a later laxative drug products. This proposal is Sodium phosphates oral solution and date. part of the ongoing review of OTC drug sodium phosphates enema 4, Based on new data submitted since products conducted by FDA. Elsewhere respectively, are the current United the January 15, 1985, and the March 31, in this issue of the Federal Register the States Pharmacopeia (USP) names for 1994, proposals were published, the agency is finalizing the package size the oral and rectal dosage forms of the agency is proposing in this document limitation and warning prior to the combination of sodium phosphates additional general and professional completion of the final monograph for ingredients. labeling for oral and rectal sodium OTC laxative drug products. In the Federal Register of March 31, phosphates products for OTC laxative DATES: Submit written comments or 1994 (59 FR 15139), the agency use. In the Federal Register of February objections by August 19, 1998. proposed to amend the tentative final 27, 1997 (62 FR 9024), FDA proposed to ADDRESSES: Submit written comments monograph for OTC laxative drug establish a standardized format for the to the Dockets Management Branch products to limit the OTC container size labeling of OTC drug products. When (HFA–305), Food and Drug for sodium phosphates oral solution to the agency finalizes that proposal, the Administration, 12420 Parklawn Dr., not greater than 90 milliliters (mL). The agency will also amend the final version rm. 1–23, Rockville, MD 20857. agency noted that the major trade of the rule proposed herein, as needed, FOR FURTHER INFORMATION CONTACT: product containing sodium phosphates to conform to the final labeling rule. Cheryl A. Turner, Center for Drug oral solution was marketed in 45-mL, Copies of previous rulemakings Evaluation and Research (HFD–560), 90-mL, and 240-mL bottles. The discussed above and information that Food and Drug Administration, 5600 purgative dose or dose used for has come to the agency’s attention since Fishers Lane, Rockville, MD 20857, colonoscopy is 45 mL. Because the publication of the proposals are on 301–827–2222. product was available in three sizes, the public display in the Dockets manufacturer’s labeling advised SUPPLEMENTARY INFORMATION: Management Branch (address above). physicians to prescribe by volume and I. Background not to prescribe by the bottle and not to II. The Agency’s Labeling Proposals for Sodium Phosphates In the Federal Register of March 21, exceed the recommended dosage, as 1975 (40 FR 12902), FDA published, serious side effects may occur. Despite A. Introduction this labeling, the multiple container under 21 CFR 330.10(a)(6), an advance One comment informed the agency of sizes available in the marketplace have notice of proposed rulemaking to modifications made in the labeling of its caused consumer confusion and appear establish a monograph for OTC laxative, rectal enema sodium phosphates to have been involved in several antidiarrheal, emetic, and antiemetic product. The comment had expanded consumer deaths (59 FR 15139 at drug products, together with the the professional labeling to include 15140). recommendations of the Advisory additional warning statements regarding Review Panel on OTC Laxative, Because of the reported cases of accidental overdosing and the confusion use in patients with a colostomy, Antidiarrheal, Emetic, and Antiemetic congenital megacolon, imperforate anus, Drug Products (the Panel), which was that has occurred between 240-mL and 90-mL container sizes, the agency impaired renal function, heart disease, the advisory review panel responsible congestive heart failure, preexisting for evaluating data on the active proposed that the 240-mL size container of sodium phosphates oral solution electrolyte disturbances (such as ingredients in these classes. The Panel dehydration or those secondary to the recommended monograph status for should no longer remain in the OTC marketplace. In the interest of safety, the use of diuretics), or in patients using phosphate salts, such as sodium calcium channel blockers, diuretics, or biphosphate 1 and sodium phosphate 2 agency proposed to limit the maximum OTC container size for this product to other medications that may affect (40 FR 12902 at 12940). electrolyte levels, as hypocalcemia, The agency’s proposed regulation, in 90 mL. The agency proposed to include the hyperphosphatemia, hypernatremia, the form of a tentative final monograph, and acidosis may occur. The comment for OTC laxative drug products was package size limitation and a warning (informing consumers not to exceed the cited several references (Refs. 1, 2, and recommended dosage unless directed by 3) to support its warning statements. 1 The Panel designated this ingredient ‘‘sodium The professional labeling also included biphosphate.’’ However, monobasic sodium phosphate is currently the official name for this 3 Sodium phosphates oral solution is the official information on the treatment of ingredient in the USP Dictionary of USAN and name for a solution of dibasic sodium phosphate electrolyte imbalances. The comment International Drug Names, 1997. and monobasic sodium phosphate in the U.S. stated that the labeling no longer 2 The Panel designated this ingredient ‘‘sodium Pharmacopeia 23/National Formulary 18, 1995. recommends the use of this enema phosphate.’’ However, dibasic sodium phosphate is 4 Sodium phosphates enema is the official name currently the official name for this ingredient in the for a solution of dibasic sodium phosphate and product in children under 2 years of USP Dictionary of USAN and International Drug monobasic sodium phosphate in the U.S. age. The comment mentioned that a Names, 1997. Pharmacopeia 23/National Formulary 18, 1995. 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 ‘‘Do not use’’ (these three words in bold hemorrhoids (Refs. 19, 20, and 23). The retail carton. print) ‘‘in patients with congestive heart authors believed that the rectal injury The agency agrees with the comment failure.’’ was compounded due to the necrotizing ‘‘Use with caution’’ (these three words in effect of the sodium phosphates on the that the professional labeling for these bold print) ‘‘in patients with impaired renal sodium phosphates products should be function, heart disease, acute myocardial rectal tissue. Other reports (Refs. 19, 20, expanded to include more information infarction, unstable angina, preexisting and 23 through 26) indicate that for health professionals to ensure safe electrolyte disturbances (such as dehydration following an enema tip injury to the use. As a result of the comment’s or those secondary to the use of diuretics), rectum, the presence of sodium additional warnings, the agency has the elderly, or people taking drugs that may phosphates causes a pronounced reevaluated all of the labeling for affect electrolyte levels.’’ inflammatory response and tissue sodium phosphates products (oral and The agency is also including the damage which, if untreated, can rectal). The agency notes that the following information regarding produce serious consequences. Based on comment included calcium channel prevention and treatment of an the above, the agency is proposing to blockers in its professional warning. electrolyte imbalance. add the following warnings in the However, the agency is not aware of any ‘‘Monitor electrolytes.’’ (these two words in professional labeling in proposed bold print) ‘‘Give sufficient fluid replacement § 334.80(b)(2)(ii) for sodium phosphates specific data to show that sodium with all oral and rectal sodium phosphates phosphates products should not be used products to prevent dehydration.’’ ‘‘What can enemas to inform health professionals to in patients taking calcium channel occur:’’ (these three words in bold print) carefully monitor use in certain blockers. Therefore, calcium channel ‘‘Hypocalcemia, hyperphosphatemia, individuals or not to use at all. This blockers will not be included in the hypernatremia, hypokalemia, and acidosis. information is also presented in the new professional warning for sodium These conditions are more likely to occur format using specific headings: phosphates products at this time. when more than one dose of sodium ‘‘Do not use’’ (these three words in bold phosphates is given in a 24-hour period.’’ print) ‘‘sodium phosphates enema in B. Professional Labeling ‘‘What you should do:’’ (these four words children under 2 years of age or in patients in bold print) ‘‘Advise people to follow with congenital megacolon or imperforate In § 334.80(b)(2) of the tentative final recommended dose. Treatment of electrolyte anus because of the risk of hyperosmotic monograph for OTC laxative drug imbalance may require immediate medical dehydration and hyperphosphatemia.’’ products (50 FR 2124 at 2157), the intervention with appropriate electrolyte and ‘‘Stop using’’ (these two words in bold agency proposed the following warnings fluid replacement. (Some examples of print) ‘‘if there is resistance to the enema tip. in the professional labeling for products references for treatment of this condition are Forcing the tip into the rectum can result in containing sodium phosphates: ‘‘Do not Fonkalsrud, E., and J. Keen, Hypernatremic a serious injury that requires immediate Dehydration Hypertonic Enemas in medical attention.’’ use in patients with megacolon, as ‘‘Use sodium phosphates enema with hypernatremic dehydration may occur. Congenital Megacolon, The Journal of the American Medical Association, 199:584586, extreme caution’’ (these seven words in bold Use with caution in patients with 1967, and Edmondson, S., and T. D. print) ‘‘in patients with a colostomy or atonic impaired renal function.’’ The Almquist, Iatrogenic Hypocalcemic Tetany, colon (because of the risk of hyperosmotic comment’s labeling and information in Annals of Emergency Medicine, 19:938–940, dehydration and hyperphosphatemia) or with the literature provide a basis to expand 1990.)’’ a rectal abnormality, such as hemorrhoids this warning. Individuals with impaired The agency is including additional (because sodium phosphates can cause renal function (Refs. 4 through 8, warnings for rectal sodium phosphates serious damage to the rectal mucosa if an enema tip injury occurs). Using more than including the elderly (Ref. 5)), heart products because of reports of its misuse one sodium phosphates enema in a 24-hour disease (Refs. 8, 9, and 10), acute in certain individuals by health period can cause serious electrolyte myocardial infarction (Refs. 11 and 12), professionals. Fatal or life-threatening problems.’’ unstable angina (Ref. 12), dehydration consequences have resulted from excess The ‘‘Do not use’’ warning for sodium (Refs. 1 and 9), or who are on diuretics dosages of sodium phosphates enemas phosphates enemas in (Ref. 10) are at risk for an electrolyte in adults (Refs. 4, 6, and 14) and in § 334.80(b)(2)(ii)(A) may be combined imbalance to occur with use of oral and young children (Refs. 10, 15, and 16). with the ‘‘Do not use’’ warning for all rectal sodium phosphates products. The agency notes that many of these sodium phosphates products in Sodium phosphates can cause adverse effects occurred when sodium § 334.80(b)(2)(i)(A). The warning alterations in serum levels of sodium, phosphates enemas were used in proposed for sodium phosphates potassium, phosphate, chloride, and children under 2 years of age. Sodium products in § 334.80(b)(2) of the calcium and, in some people, such phosphates enemas have also been tentative final monograph, which stated changes can be life threatening. The misused in individuals with colon ‘‘Do not use in patients with megacolon, reduction of calcium levels reflects abnormalities (Refs. 1, 4, 10, 17, and 18) as hypernatremic dehydration may changes in ionized calcium (Ref. 13). and rectal abnormalities (Refs. 5, 19, occur. Use with caution in patients with Hypocalcemia with subsequent low and 20). Individuals with a functional impaired renal function,’’ is superseded levels of ionized calcium may result in abnormality of the colon, e.g., a by the warnings in this amendment. neuromuscular irritability, heart block, colostomy (Refs. 10, 21, and 22), The agency notes that the comment and cardiovascular failure (Ref. 13). imperforate anus (Refs. 4 and 21), atonic stated that a summarized version of the Therefore, the agency has determined colon (Ref. 4), or congenital megacolon professional labeling will appear on the that the warnings in the professional (Refs. 1, 4, 10, and 21) are at risk for product’s retail package. Professional labeling for oral and rectal sodium hyperosmotic dehydration and labeling is labeling provided to health phosphates products in proposed hyperphosphatemia with the use of professionals but not to the general § 334.80(b)(2) (redesignated as sodium phosphates enemas. Such public. Therefore, a summarized version § 334.80(b)(2)(i) in this proposal) should individuals have a tendency to retain of this professional labeling should not be expanded. The agency has made an the enema for a prolonged period of appear on the retail package. As effort to present the warning time, and considerable absorption of the discussed in section II.C of this information in a new format using phosphate ion occurs. Several cases of document, the agency has developed specific headings to make it clearer and rectal gangrene have occurred after an labeling for sodium phosphates more readable as follows: enema nozzle injury in individuals with 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 proposing to revise the directions for The agency is proposing a new these products. oral sodium phosphates products in direction in § 334.58(d)(5)(ii)(C) for new § 201.307(b)(3)(ii) (21 CFR sodium phosphates rectal products. A C. OTC Labeling 201.307(b)(3)(ii)) (designated as sodium phosphates enema can cause In § 334.58(c)(2)(i) of the tentative § 334.58(d)(5)(i) in this proposal) and in serious damage to the rectal mucosa if final monograph (50 FR 2124 at 2155), proposed § 334.58(d)(6) and (d)(7) to be the enema tip causes a rectal injury the agency proposed the following consistent with other oral OTC laxative (Refs. 19, 20, and 23). If the enema tip warning for products containing sodium drug products. (See section II.D of this perforates the rectum, antibiotic phosphates: ‘‘Do not use this product if document.) Therefore, for consistency, treatment or a temporary colostomy may you have kidney disease, unless the proposed warning in be needed to prevent sepsis (Refs. 23 directed by a doctor.’’ The agency is § 334.58(c)(2)(ii) for oral sodium through 26, and 31). All rectal bleeding proposing to expand the warning for phosphates is revised to state: ‘‘Do not resulting from an enema tip injury oral and rectal products that contain give to children under 6 years of age, should be medically evaluated because sodium phosphates because consumers without asking a doctor.’’ rectal perforations can be painless (Refs. who have kidney disease (Refs. 4 In § 334.58(c)(2)(iii) of the tentative 20, 25, and 31). Therefore, the new through 7), heart problems (Refs. 8 final monograph (50 FR 2124 at 2155), direction states: ‘‘Stop using if tip is through 12), or are dehydrated (Refs. 1 the agency proposed the following hard to insert. Forcing the tip into the and 9) should not use sodium warning for sodium phosphates enemas: rectum can cause injury (especially if phosphates products, unless directed by ‘‘Do not give to children under 2 years you have hemorrhoids). If enema tip a doctor. causes rectal bleeding or pain, get The agency has also determined that of age unless directed by a doctor.’’ The agency also proposed the following immediate medical care.’’ a new warning is needed to restrict the The agency is aware that labeling that number of days that all oral and rectal direction for sodium phosphates enemas in § 334.58(d)(5)(ii) (50 FR 2124 at was submitted to the Panel (Ref. 32) and sodium phosphates products can be currently marketed labeling (Ref. 33) for 2155): ‘‘* * * Children under 2 years of used, unless directed by a doctor. The oral sodium phosphates products age: consult a doctor.’’ However, Panel in its report (40 FR 12902 at contain dosages for children 5 to 9 years because of adverse effects that have 12941) and the agency in the tentative of age, and for children 10 and 11 years occurred when sodium phosphates final monograph (50 FR 2124 at 2153) of age. The Panel in its report (40 FR enemas were used in children under 2 recommended that the use of sodium 12902 at 12940) and the agency in the years of age, the agency is revising the phosphates be restricted to 1 week (7 tentative final monograph (50 FR 2124 warning and direction statements. days). However, the agency has at 2155) recommended dosages of oral Therefore, in § 334.58(c)(2)(iii) of this reviewed new data indicating that sodium phosphates products for these proposal, the revised warning for sodium phosphates can cause age groups. Elsewhere, in this issue of electrolyte imbalances within 24 hours sodium phosphates rectal products the Federal Register, the agency after the initial dose is taken (Refs. 4, 11, states: ‘‘Do not use in children under 2 included the above age ranges in the and 12) (also see the final rule for oral years of age.’’ The corresponding directions in new § 201.307(b)(3)(ii). and rectal OTC sodium phosphates drug direction, which appears in The agency notes that the directions for products published elsewhere in this § 334.58(d)(5)(ii)(A) in this proposal, is sodium phosphates oral solution issue of the Federal Register). These revised to state: ‘‘* * * Do not use in contain separate dosages for children 10 blood level changes have occurred in children under 2 years of age.’’ The and 11 years of age, and for children 5 individuals with no underlying renal agency believes it is necessary to have to 9 years of age. These age ranges are failure or active heart disease (Refs. 11, this information in both the warning not consistent with age ranges used for 12, and 27). The agency is concerned and direction sections of the labeling the majority of OTC laxative drug that daily use of sodium phosphates because of the adverse effects that can products, which recommend dosages for products for 7 days may cause occur when sodium phosphates enemas children 6 to 11 years of age. significant changes in the sodium, are used in children under 2 years of Therefore, the agency is proposing to potassium, phosphate, chloride, and/or age. revise the directions for oral sodium calcium blood levels. In the interest of D. Directions phosphates products in new consumer safety and to help reduce the § 201.307(b)(3)(ii) (designated as risk of adverse effects that can occur Effectiveness is not increased when a § 334.58(d)(5)(i) in this proposal), and in from sequential doses of sodium sodium phosphates enema is retained proposed § 334.58(d)(6) and (d)(7) to be phosphates, the agency believes that use more than 5 minutes (Refs. 28, 29, and consistent with other oral OTC laxative of sodium phosphates should be limited 30). Data indicate that a sodium drug products. The proposed directions to 3 days instead of 7 days. The revised phosphates enema is usually expelled in § 334.58(d)(5)(i) state: warning for oral and rectal sodium from the rectum within 20 minutes * * * Children 6 to 9 years of age: Oral phosphates, which appears in proposed (Refs. 28, 29, and 30) and that increased dosage is dibasic sodium phosphate 0.86 to § 334.58(c)(2)(i), states: ‘‘Do not use if’’ blood levels of phosphorus and sodium 1.89 g and monobasic sodium phosphate 2.2 (these four words in bold print) ‘‘you and decreased levels of calcium can to 5.05 g (5 to 10 mL dibasic sodium occur within several hours (Refs. 13, 17, phosphate/monobasic sodium phosphate oral have kidney disease, heart problems, or solution) as a single daily dose. ‘Do not take are dehydrated, or for more than 3 days, and 30) if the enema is retained. more than 10 mL (2 teaspoonfuls) in a 24- without asking a doctor.’’ Therefore, the agency is proposing a hour period.’ Children under 6 years of age: In § 334.58(c)(2)(ii) of the tentative new direction for sodium phosphates ask a doctor. final monograph (50 FR 2124 at 2155), rectal products in § 334.58(d)(5)(ii)(B) in The proposed directions in the agency proposed the following this proposal, which states: ‘‘If no urge § 334.58(d)(6) for products containing warning for oral dosage forms of sodium is felt after 5 minutes of using, try to dibasic sodium phosphate identified in phosphates identified in § 334.16(d), (e), empty bowel. Call a doctor promptly if § 334.16(e) state: ‘‘* * * Children 6 to 9 or (f): ‘‘Do not give to children under 5 no liquid comes out of the rectum after years of age: Oral dosage is 0.86 to 1.89 years of age unless directed by a 30 minutes because dehydration could g in a single daily dose. Children under doctor.’’ However, the agency is occur.’’ 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 Preparation,’’ The Journal of the American Avoidable Problem,’’ American Journal of products containing monobasic sodium Medical Association, 216:147–148, 1971. Physical Medical and Rehabilitation, 67:186– phosphate identified in § 334.16(f) state: 4. Korzets, A. et al., ‘‘Life-Threatening 188, 1988. ‘‘* * * Children 6 to 9 years of age: Oral Hyperphosphatemia and Hypocalcemic 21. Honig, P. J., and P. G. Holtzapple, Tetany Following the Use of Fleet Enemas,’’ ‘‘Hypocalcemic Tetany Following Hypertonic dosage is 1.12 to 5.05 g in a single daily Journal of the American Geriatric Society, Phosphate Enemas,’’ Clinical Pediatrics, dose. Children under 6 years of age: ask 40:620–621, 1992. 14:678–679, 1975. a doctor.’’ 5. Grosskopf, I. et al., 22. Hunter, F. M. et al., ‘‘Hyperphosphataemia and Hypocalcaemia E. Time to Effect ‘‘Hyperphosphataemia after Enemas in Induced by Hypertonic Phosphate Enema— Childhood: Prevention and Treatment,’’ The agency is proposing to revise the An Experimental Study and Review of the Archives of Diseases in Childhood, 68:233– time to effect statement in proposed Literature,’’ Human and Experimental 234, 1993. § 334.58(b)(2) for sodium phosphates Toxicology, 10:351–355, 1991. 23. Turell, R., ‘‘Laceration to Anorectum 6. Biberstein, M., and B. A. Parker, rectal products from 2 to 15 minutes to Incident to Enema,’’ Archives of Surgery, ‘‘Enema-Induced Hyperphosphatemia,’’ The 81:953–954, 1960. 1 to 5 minutes. In three studies (Refs. American Journal of Medicine, 79:645–646, 24. Bell, A. M., ‘‘Colonic Perforation with 28, 29, and 30), 98 subjects (280 1985. a Phosphate Enema,’’ Journal of the Royal observations) were evaluated to 7. Oxnard, S. C., J. O’Bell, and W. E. Grupe, Society of Medicine, 83:54–55, 1990. determine the time to effect following ‘‘Severe Tetany in an Azotemic Child Related 25. Peitsch, J. B., H. M. Shizgal, and J. L. use of sodium phosphates enema. In 98 to a Sodium Phosphate Enema,’’ Pediatrics, Meakins, ‘‘Injury by Hypertonic Phosphate percent of the observations (33 subjects 53:105–106, 1974. Enema,’’ Canadian Medical Association accounted for 261/280 observations), the 8. Wiberg, J. J., G. G. Turner, and F. Q. Journal, 116:1169–1170, 1977. Nuttall, ‘‘Effect of Phosphate or Magnesium 26. Hool, G. J., E. L. Bokey, and M. T. reported time to effect was within 10 Cathartics on Serum Calcium,’’ Archives of minutes. In 83 percent of the Pheils, ‘‘Enema-Nozzle Injury of the Internal Medicine, 138:1114–1116, 1978. Rectum,’’ The Medical Journal of Australia, observations, the time to effect was 9. Gilman, A. et al., The Pharmacological 1:364 and 381, 1980. between 1 and 5 minutes. The average Basis of Therapeutics, 8th ed., Pergamon 27. Clarkston, W. K. et al., ‘‘A Single Blind time to effect was 4 to 5 minutes and the Press, New York, p. 919, 1992. Comparison of Serum Electrolytes, Serum mode was 3 to 5 minutes. The data do 10. Martin, R. R. et al., ‘‘Fatal Poisoning Phosphorus, Serum Calcium, and Ventricular not indicate that sodium phosphates is from Sodium Phosphate Enema—Case Report Arrhythmias in Outpatients Receiving more effective if the solution is retained and Experimental Study,’’ The Journal of the Nulytely Versus Fleet Phospho-Soda more than 5 minutes (Refs. 28, 29, and American Medical Association, 257:2190– Preparation for Colonoscopy: Preliminary 2192, 1987. Results’’ (unpublished study), pp. 1928, 30). Therefore, the agency is proposing 11. Vanner, S. J. et al., ‘‘A Randomized to revise § 334.58(b)(2) to state: ‘‘This 1994, OTC Vol. 090TFM4, Docket No. 78N– Prospective Trial Comparing Oral Sodium 036L, Dockets Management Branch. product generally produces bowel Phosphate with Standard Polyethylene 28. Page, S. G., C. R. Riley, and H. B. Haag, movement in 1 to 5 minutes.’’ Glycol-Based Lavage Solution (GoLytely) in ‘‘A Comparative Clinical Study of Several The agency invites specific comments the Preparation of Patients for Colonoscopy,’’ Enemas,’’ The Journal of the American on these proposed labeling statements. The American Journal of Gastroenterology, Medical Association, 157:1208–1210, 1955. The agency will discuss its decision on 85:422–427, 1990. 29. Stempien, S. J., ‘‘Double-Blind these labeling proposals in a future 12. Kolts, B. E. et al., ‘‘A Comparison of the Evaluation of Sorbitol, Phosphate, and Effectiveness and Patient Tolerance of Oral Dextrose Enemas at Sigmoidoscopy,’’ issue of the Federal Register. Until the Sodium Phosphate, Castor Oil, and Standard agency makes a final determination on Gastroenterology, 36:830–831, 1959. Electrolyte Lavage for Colonoscopy or 30. Bodi, T., and G. H. Frey, ‘‘Clinical these labeling statements, the agency Sigmoidoscopy Preparation,’’ The American Evaluations of Small-Volume Enemas,’’ encourages all manufacturers of sodium Journal of Gastroenterology, 88:1218–1223, Pennsylvania Medical Journal, 68:35–38, phosphates products voluntarily to label 1993. 1965. their products to include the proposed 13. Cagir, B. et al., ‘‘Hypocalcemia in 31. Weiss, Y., P. Grunberger, and S. labeling statements. Because FDA is Surgical Critical Care Patients: Measurements Aronowitz, ‘‘Asymptomatic Rectal encouraging that the proposed labeling of Ionized Calcium,’’ Contemporary Surgery, Perforation with Retroperitoneal statements be used on a voluntary basis 45:71–78, 1994. Emphysema,’’ American Society of Colon 14. Rohack, J. J., B. R. Mehta, and K. and Rectal Surgeons, 24:545–547, 1980. at this time, the agency will give Subramanyam, ‘‘Hyperphosphatemia and manufacturers ample time after 32. OTC Vol. 090011. Hypocalcemic Coma Associated with 33. Labeling for Fleet Phospho-Soda, in publication of a final rule to use up any Phosphate Enema,’’ Southern Medical OTC Vol. 090TFM3, Docket No. 78N–036L, labeling implemented in conformance Journal, 78:1241–1242, 1985. Dockets Management Branch. with this document. 15. Edmondson, S., and T. D. Almquist, ‘‘Iatrogenic Hypocalcemic Tetany,’’ Annals of IV. Summary of the Agency’s Proposal III. References Emergency Medicine, 19:938–940, 1990. for OTC Laxative Drug Products The following references have been 16. Sotos, J. F. et al., ‘‘Hypocalcemic Coma Containing Sodium Phosphates Following Two Pediatric Phosphate placed on display in the Dockets Enemas,’’ Pediatrics, 60:305–307, 1977. Based on new information, the agency Management Branch (address above) 17. Spinrad, S. et al., ‘‘Treating is proposing changes in the labeling for and may be seen by interested persons Constipation with Phosphate Enema: An oral and rectal sodium phosphates drug between 9 a.m. and 4 p.m., Monday Unnecessary Risk,’’ Israel Journal of Medical products. A summary of the changes through Friday. Sciences, 25:237–238, 1989. proposed in this document follows. 1. Fonkalsrud, E., and J. Keen, 18. Schuchmann, G. D., and P. J. Barcia, 1. The agency is revising proposed ‘‘Hypernatremic Dehydration Hypertonic ‘‘Phosphate Absorption from Fleet Enemas in § 334.16(d), (e), and (f) of the Enemas in Congenital Megacolon,’’ The Adults,’’ Current Surgery, 46:120–122, 1989. monograph to use the current USP Journal of the American Medical Association, 19. Sweeney, J. L. et al., ‘‘Rectal Gangrene: names for dibasic sodium phosphate/ 199:584–586, 1967. A Complication of Phosphate Enema,’’ 2. Goodman, L., and A. Gilman, The Medical Journal of Australia, 144:374–375, monobasic sodium phosphate (sodium Pharmacological Basis of Thearpeutics, 6th 1986. phosphates) drug products. (See section ed., McGraw Hill, New York, p. 1005, 1980. 20. Saltzstein, R. J., E. Quebbeman, and J. I of this document.) 3. McConnell, T. H., ‘‘Fatal Hypocalcemia L. Melvin, ‘‘Anorectal Injuries Incident to 2. The agency is revising the warning from Phosphate Absorption from Laxative Enema Administration. A Recurring 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 sodium phosphates proposed in consumers use, and health professionals phosphates identified in § 334.16(d), (e), § 334.80(b)(2) to include additional ‘‘Do recommend, these products. and (f) to state: ‘‘Do not give to children not use’’ and ‘‘Use with caution’’ The agency has been informed that under 6 years of age, without asking a warnings. The agency is also including relabeling costs of the type required by doctor.’’(See section II.C of this new information about monitoring this proposed rule (changes to both document.) electrolytes and treating electrolyte consumer and professional labeling) 3. The agency is revising the imbalances. The new warnings and generally average about $3,000 to $4,000 directions for oral sodium phosphates in other information appear in per stock keeping unit (SKU) new § 201.307(b)(3)(ii) (designated as § 334.80(b)(2)(i) and (b)(2)(ii). (See (individual products, packages, and § 334.58(d)(5)(i) in this proposal) and in section II.B of this document.) sizes). The agency is aware of 3 proposed § 334.58(d)(6) and (d)(7) to be 10. The agency has made an effort to manufacturers that together produce 4 consistent with other oral OTC laxative shorten and simplify some of the SKU’s of oral sodium phosphates drug drug products. The directions will labeling, e.g., by using the phrase products and approximately 125 SKU’s include oral dosages for children 6 years ‘‘without asking a doctor’’ instead of of rectal sodium phosphates drug of age and older and state to ask a doctor ‘‘unless directed by a doctor.’’ The products. There may be a few additional for children under 6 years of age. (See agency has also proposed a new format small manufacturers or a few additional section II.D of this document.) for professional labeling. The agency products in the marketplace that are not 4. The agency is changing the ‘‘time believes that these changes will provide identified in the sources FDA reviewed. to effect’’ statement proposed in a clear and readable format for these Assuming that there are about 130 § 334.58(b)(2) for rectal dosage forms of labeling statements. FDA is inviting affected OTC SKU’s in the marketplace, sodium phosphates from 2 to 15 specific comments on this labeling total one-time costs of relabeling would minutes to 1 to 5 minutes. (See section format and on the wording of these be $390,000 to $520,000. II.E of this document.) statements. The agency also believes that actual 5. The agency is expanding the costs could be lower for several reasons. warning for oral and rectal sodium V. Analysis of Impacts phosphates proposed in § 334.58(c)(2)(i) FDA has examined the impacts of the First, most of the label changes will be to state: ‘‘Do not use if’’ (these four proposed rule under Executive Order made by private label manufacturers words in bold print) ‘‘you have kidney 12866 and the Regulatory Flexibility Act that tend to use simpler and less disease, heart problems, or are (5 U.S.C. 601–612). Executive Order expensive labeling. Second, labeling dehydrated, or for more than 3 days, 12866 directs agencies to assess all costs changes would not be required until the without asking a doctor.’’ (See section and benefits of available regulatory final monograph for OTC laxative drug II.C of this document.) alternatives and, when regulation is products is issued and becomes 6. The agency is revising the warning necessary, to select regulatory effective. The agency is proposing a 12- proposed for rectal dosage forms of approaches that maximize net benefits month implementation period that sodium phosphates in § 334.58(c)(2)(iii) (including potential economic, would allow the manufacturers to which stated, ‘‘Do not give to children environmental, public health and safety, coordinate these changes with routinely under 2 years of age unless directed by and other advantages; distributive scheduled label printing and/or other a doctor,’’ to read: ‘‘Do not use in impacts; and equity). Under the revisions required by the final children under 2 years of age.’’ The Regulatory Flexibility Act, if a rule has monograph for OTC laxative drug agency is also revising the direction a significant economic impact on a products. Thus, relabeling costs for proposed for rectal sodium phosphates substantial number of small entities, an these products would be mitigated or in § 334.58(d)(5)(ii) which stated, agency must analyze regulatory options reduced by the cost of other labeling ‘‘Children under 2 years of age: consult that would minimize any significant changes that the final monograph will a doctor,’’ with a new direction in impact of the rule on small entities. also require. § 334.58(d)(5)(ii)(A) that states: ‘‘Do not Title II of the Unfunded Mandates The proposed rule would not require use in children under 2 years of age.’’ Reform Act (2 U.S.C. 1501 et seq.) any new reporting and recordkeeping (See section II.C of this document.) requires that agencies prepare a written activities. Therefore, no additional 7. The agency is proposing new statement and economic analysis before professional skills are needed. There are directions for rectal dosage forms of proposing any rule that may result in an no other Federal rules that duplicate, sodium phosphates in expenditure in any 1 year by State, overlap, or conflict with the proposed § 334.58(d)(5)(ii)(B) that state: ‘‘If no local, and tribal governments, in the rule. urge is felt after 5 minutes of using, try aggregate, or by the private sector, of The agency considered but rejected to empty bowel. Call a doctor promptly $100 million (adjusted annually for several labeling alternatives: (1) if no liquid comes out of the rectum inflation). Voluntary relabeling, (2) publication of after 30 minutes because dehydration The agency believes that this the labeling information in the FDA could occur.’’ (See section II.D of this proposed rule is consistent with the Drug Bulletin or professional journals, document.) principles set out in the Executive Order and (3) an exemption from coverage for 8. The agency is proposing new and in these two statutes. The purpose small entities. The agency does not directions in § 334.58(d)(5)(ii)(C) for of this proposed rule is to add warning consider the first or third alternative rectal dosage forms of sodium and direction statements to the general acceptable because they do not assure phosphates that state: ‘‘Stop using if tip OTC and health professional (for health that consumers or health professionals is hard to insert. Forcing the tip into the professionals only) labeling of oral and will have the most recent needed rectum can cause injury (especially if rectal OTC sodium phosphates drug information for safe and effective use of you have hemorrhoids). If enema tip products. These warning and direction these sodium phosphates drug products. causes rectal bleeding or pain, get statements concern product toxicity and The agency considers the second immediate medical care.’’ (See section are intended to help ensure the safe and alternative useful and may proceed with II.D of this document.) effective use of all OTC sodium such publications. However, such 9. The agency is revising the phosphates drug products. Potential publications do not provide a professional labeling for oral and rectal benefits include reduced toxicity when permanent labeling requirement, which 27892 Federal Register / Vol. 63, No. 98 / Thursday, May 21, 1998 / Proposed Rules the agency considers necessary for these economic impact that this rulemaking Therefore, under the Federal Food, products. would have on OTC laxative drug Drug, and Cosmetic Act and under This proposed rule may have a products containing sodium authority delegated to the Commissioner significant economic impact on the phosphates. Comments regarding the of Food and Drugs, it is proposed that manufacturers of these products, all of impact of this rulemaking on OTC 21 CFR part 334 (proposed in the which are considered to be small laxative drug products containing Federal Register of January 15, 1985, 50 entities, using the U.S. Small Business sodium phosphates should be FR 2124) be amended as follows: Administration designations for this accompanied by appropriate industry (750 employees). The agency documentation. The agency is providing PART 334ÐLAXATIVE DRUG believes that any other unidentified a period of 90 days from the date of PRODUCTS FOR OVER-THE- manufacturer of these products is also publication of this proposed rulemaking COUNTER HUMAN USE likely to be a small entity. These in the Federal Register for development 1. The authority citation for 21 CFR manufacturers will need to change the and submission of comments on this part 334 continues to read as follows: information panel of each affected subject. The agency will evaluate any sodium phosphates SKU and print new comments and supporting data that are Authority: 21 U.S.C. 321, 351, 352, 353, professional labeling. Among the steps received and will reassess the economic 355, 360, 371. the agency is taking to minimize the impact of this rulemaking in the 2. Section 334.16 is amended by impact on these small entities are: (1) To preamble to the final rule. revising paragraphs (d), (e), and (f) to provide 1 year for implementation to read as follows: VI. Paperwork Reduction Act of 1995 enable entities to use up existing § 334.16 Saline laxative active ingredients. labeling stock, and (2) to allow these FDA tentatively concludes that the * * * * * labeling changes to be coordinated with labeling requirements proposed in this (d) Dibasic sodium phosphate/ other labeling changes required by the document are not subject to review by monobasic sodium phosphatemarketed final monograph. The agency believes the Office of Management and Budget as a solution. that these actions should help reduce because they do not constitute a (e) Dibasic sodium phosphate. the relabeling cost for small entities. ‘‘collection of information’’ under the (f) Monobasic sodium phosphate. The agency considered but rejected Paperwork Reduction Act of 1995 (44 3. Section 334.58 is amended by both a shorter and a longer U.S.C. 3501 et seq.). Rather, the revising paragraph (b)(2), by revising implementation period. While the proposed labeling statements are a paragraph (c)(2), by revising the heading agency would like to have this new ‘‘public disclosure of information of paragraph (d)(5) and text of paragraph labeling in place as soon as possible, it originally supplied by the Federal (d)(5)(i), by redesignating paragraph considers a period less than 1 year government to the recipient for the (d)(5)(ii) as (d)(5)(ii)(A) and revising difficult for manufacturers to implement purpose of disclosure to the public’’ (5 new (d)(5)(ii)(A), by adding new all of the labeling required by the final CFR 1320.3(c)(2)). paragraphs (d)(5)(ii)(B) and (d)(5)(ii)(C), monograph. The agency considered a and by revising the headings and text of longer effective date but finds it VII. Environmental Impact paragraphs (d)(6) and (d)(7) to read as unacceptable because it would not The agency has determined under 21 follows: assure that consumers have the most CFR 25.31(c) that this action is of a type recent needed information for safe and that does not individually or § 334.58 Labeling of saline laxative drug effective use of OTC sodium phosphates cumulatively have a significant effect on products. drug products at the earliest possible the human environment. Therefore, * * * * * time. Manufacturers are encouraged to neither an environmental assessment (b) * * * implement the new labeling as soon as nor an environmental impact statement (2) Rectal dosage forms. ‘‘This possible after the final monograph is is required. product generally produces bowel published. VIII. Request for Comments movement in 1 to 5 minutes.’’ The analysis shows that this proposed (c) * * * rule is not economically significant Interested persons may, on or before (2) For products containing dibasic under Executive Order 12866 and that August 19, 1998, submit written sodium phosphate or monobasic the agency has undertaken important comments or objections on the proposed sodium phosphate identified in steps to reduce the burden to small regulation to the Dockets Management § 334.16(d), (e), or (f)—(i) ‘‘Do not use entities. Nevertheless, some entities, Branch (address above). Three copies of if’’ (these four words in bold print) ‘‘you especially those private label all comments or objections are to be have kidney disease, heart problems, or manufacturers that provide labeling for submitted, except that individuals may are dehydrated, or for more than 3 days, a number of the affected products, may submit one copy. Comments should be without asking a doctor.’’ incur significant impacts. Thus, this identified with the docket number (ii) Oral dosage forms. ‘‘Do not give to economic analysis, together with other found in brackets in the heading of this children 5 years of age and under, relevant sections of this document, document and may be accompanied by without asking a doctor.’’ serves as the agency’s initial regulatory a supporting memorandum or brief. (iii) Rectal dosage forms. ‘‘Do not use flexibility analysis, as required under Received comments and objections may in children under 2 years of age.’’ the Regulatory Flexibility Act. Finally, be seen in the office above between 9 (d) * * * this analysis shows that the Unfunded a.m. and 4 p.m., Monday through (5) For products containing dibasic Mandates Act does not apply to the Friday. sodium phosphate/ monobasic sodium proposed rule because it would not FDA is proposing that any final rule phosphate identified in § 334.16(d) and result in an expenditure in any 1 year based on this proposal be effective 12 marketed as a solution—(i) Oral dosage. by State, local, and tribal governments, months after the date of its publication Adults and children 12 years of age and in the aggregate, or by the private sector, in the Federal Register. over: Oral dosage is dibasic sodium of $100 million. phosphate 3.42 to 7.56 grams and The agency invites public comment List of Subjects in 21 CFR Part 334 monobasic sodium phosphate 9.1 to regarding any substantial or significant Labeling, Over-the-counter drugs. 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 Oral dosage is 1.12 to 5.05 grams in a rectum can result in a serious injury that sodium phosphate oral solution) as a single daily dose. Children under 6 requires immediate medical attention.’’ single daily dose. ‘‘Do not take more years of age: ask a doctor. (C) ‘‘Use sodium phosphates enema than 45 mL (9 teaspoonfuls or 3 4. Section 334.80 is amended by with extreme caution’’ (these seven tablespoonfuls) in a 24-hour period.’’ redesignating paragraph (b)(2) as words in bold print) ‘‘in patients with Children 10 and 11 years of age: Oral paragraph (b)(2)(i) and revising it, and a colostomy or atonic colon (because of dosage is dibasic sodium phosphate by adding paragraph (b)(2)(ii), to read as the risk of hyperosmotic dehydration 1.71 to 3.78 grams and monobasic follows. and hyperphosphatemia) or with a sodium phosphate 4.5 to 10.1 grams (10 rectal abnormality, such as hemorrhoids § 334.80 Professional labeling. to 20 mL dibasic sodium phosphate/ (because sodium phosphates can cause monobasic sodium phosphate oral * * * * * serious damage to the rectal mucosa if solution) as a single daily dose. ‘‘Do not (b) * * * an enema tip injury occurs). Using more take more than 20 mL (4 teaspoonfuls) (2) For products containing dibasic than one sodium phosphates enema in in a 24-hour period.’’ Children 6 to 9 sodium phosphate or monobasic a 24-hour period can cause serious years of age: Oral dosage is dibasic sodium phosphate identified in electrolyte problems.’’ § 334.16(d), (e), or (f)—(i) Oral and sodium phosphate 0.86 to 1.89 gram and * * * * * monobasic sodium phosphate 2.2 to rectal dosage forms—(A) ‘‘Do not use’’ 5.05 grams (5 to 10 mL dibasic sodium (these three words in bold print) ‘‘in Dated: April 27, 1998. phosphate/monobasic sodium patients with congestive heart failure.’’ William K. Hubbard, phosphate oral solution) as a single (B) ‘‘Use with caution’’ (these three Associate Commissioner for Policy daily dose. ‘‘Do not take more than 10 words in bold print) ‘‘in patients with Coordination. mL (2 teaspoonfuls) in a 24-hour impaired renal function, heart disease, [FR Doc. 98–12054 Filed 5–20–98; 8:45 am] period.’’ Children under 6 years of age: acute myocardial infarction, unstable BILLING CODE 4160±01±F ask a doctor. angina, preexisting electrolyte (ii) Rectal enema dosage. (A) Adults disturbances (such as dehydration or and children 12 years of age and over: those secondary to the use of diuretics), DEPARTMENT OF TRANSPORTATION Enema dosage is dibasic sodium the elderly, or people taking drugs that phosphate 6.84 to 7.56 grams and may affect electrolyte levels.’’ Coast Guard monobasic sodium phosphate 18.24 to (C) ‘‘Monitor electrolytes.’’ (these two 20.16 grams in a single daily dose. words in bold print) ‘‘Give sufficient 33 CFR Part 165 Children 2 to 11 years of age: Enema fluid replacement with all oral and [CGDO1±98±002] dosage is dibasic sodium phosphate rectal sodium phosphates products to 3.42 to 3.78 grams and monobasic prevent dehydration.’’ RIN 2121±AA97 sodium phosphate 9.12 to 10.08 grams (D) ‘‘What can occur:’’ (these three Safety Zone; New York Super Boat in a single daily dose. ‘‘Do not use in words in bold print) ‘‘Hypocalcemia, Race, New York children under 2 years of age.’’ hyperphosphatemia, hypernatremia, (Manufacturers should convert these hypokalemia, and acidosis. These AGENCY: Coast Guard, DOT. conditions are more likely to occur dosages to the amount of solution to be ACTION: Notice of proposed rulemaking. used.) when more than one dose of sodium (B) ‘‘If no urge is felt after 5 minutes phosphates is given in a 24-hour SUMMARY: The Coast Guard proposes to of using, try to empty bowel. Call a period.’’ establish a temporary safety zone in the doctor promptly if no liquid comes out (E) ‘‘What you should do:’’ (these four lower Hudson River, for the New York of the rectum after 30 minutes because words in bold print) ‘‘Advise people to Super Boat Race. The temporary safety dehydration could occur.’’ follow recommended dose. Treatment of zone would be in effect on Sunday, (C) ‘‘Stop using if tip is hard to insert. electrolyte imbalance may require September 13, 1998, from 11:30 a.m. Forcing the tip into the rectum can immediate medical intervention with until 4:00 p.m. unless extended or cause injury (especially if you have appropriate electrolyte and fluid terminated sooner by the Captain of the hemorrhoids). If enema tip causes rectal replacement. (Some examples of Port, New York. The proposed safety bleeding or pain, get immediate medical references for treatment of this zone would restrict vessel traffic in the care.’’ condition are Fonkalsrud, E., and J. Lower Hudson River between Battery (6) For products containing dibasic Keen, ‘Hypernatremic Dehydration Park and Pier 76 in Manhattan. The sodium phosphate identified in Hypertonic Enemas in Congenital proposed safety zone is needed to § 334.16(e). Adults and children 12 Megacolon,’ The Journal of the protect racing participants and spectator years of age and over: Oral dosage is American Medical Association, craft from the hazards associated with 3.42 to 7.56 grams in a single daily dose. 199:584–586, 1967, and Edmondson, S., high speed powerboat racing. Children 10 to 11 years of age: Oral and T. D. Almquist, ‘Iatrogenic DATES: Comments must be received on dosage is 1.71 to 3.78 grams in a single Hypocalcemic Tetany,’ Annals of or before August 19, 1998. daily dose. Children 6 to 9 years of age: Emergency Medicine, 19:938–940, Oral dosage is 0.86 to 1.89 gram in a 1990.)’’ ADDRESSES: Comments should be single daily dose. Children under 6 (ii) Rectal dosage forms. (A) ‘‘Do not mailed to Lieutenant Junior Grade Alma years of age: ask a doctor. use’’ (these three words in bold print) Kenneally, Waterways Oversight (7) For products containing ‘‘sodium phosphates enema in children Branch, Coast Guard Activities New monobasic sodium phosphate identified under 2 years of age or in patients with York, 212 Coast Guard Drive, Staten in § 334.16(f). Adults and children 12 congenital megacolon or imperforate Island, New York 10305. years of age and over: Oral dosage is 4.5 anus because of the risk of hyperosmotic FOR FURTHER INFORMATION CONTACT: to 20.2 grams in a single daily dose. dehydration and hyperphosphatemia.’’ Lieutenant Junior Grade Alma Children 10 to 11 years of ages: Oral (B) ‘‘Stop using’’ (these two words in Kenneally, Waterways Oversight dosage is 2.25 to 10.1 grams in a single bold print) ‘‘if there is resistance to the Branch, Coast Guard Activities New daily dose. Children 6 to 9 years of age: enema tip. Forcing the tip into the York (718) 354–4195.