§ 201.307 21 CFR Ch. I (4–1–10 Edition)

publication of this section, with re- tainer was mistakenly used instead of spect to the marketing of uncoated the 45-mL or 90-mL container. The tablets containing potassium chloride Food and Drug Administration is lim- or other potassium salts which supply iting the amount of sodium phosphates 100 milligrams or more of potassium oral solution to not more than 90 mL (3 per tablet or with respect to liquid ounces (oz)) per OTC container because preparations containing potassium of the serious health risks associated chloride or other potassium salts which with the ingestion of larger than in- supply 20 milligrams or more of potas- tended doses of this product. Further, sium per milliliter, labeled or intended because an overdose of either oral or for human use, unless all the following rectal enema sodium phosphates can conditions are met: cause an electrolyte imbalance, addi- (1) The labeling of the drug bears the tional warning and direction state- prescription statement quoted in sec- ments are required for the safe use of tion 503(b)(4) of the Federal Food, any OTC laxative drug product con- Drug, and Cosmetic Act; and taining sodium phosphates. (2) The labeling on or within the (b) Any OTC drug product for lax- package from which the drug is to be ative or bowel cleansing use containing dispensed bears adequate information sodium phosphates as an active ingre- for its use by practitioners in accord dient when marketed as described in with the ‘‘full disclosure’’ labeling re- paragraph (a) of this section is mis- quirements of § 201.100 of this chapter, branded within the meaning of section including a recommendation that pa- 502 of the Federal Food, Drug, and Cos- tients be directed to dissolve any such metic Act unless packaged and labeled tablets in an appropriate amount of as follows: liquid and to dilute any such liquid (1) Package size limitation for so- preparations adequately to assure dium phosphates oral solution: Con- against gastrointestinal injury associ- tainer shall not contain more than 90 ated with the oral ingestion of con- mL (3 oz). centrated potassium salt preparations. (2) Warnings. The following sentences [40 FR 13998, Mar. 27, 1975, as amended at 55 shall appear in boldface type as the FR 11576, Mar. 29, 1990; 67 FR 4906, Feb. 1, first statement under the heading 2002] ‘‘Warnings.’’ (i) Oral dosage forms. ‘‘Taking more § 201.307 Sodium phosphates; package than the recommended dose in 24 hours size limitation, warnings, and direc- can be harmful.’’ tions for over-the-counter sale. (ii) Rectal enema dosage forms. (a) Reports in the medical literature ‘‘Using more than one enema in 24 and data accumulated by the Food and hours can be harmful.’’ Drug Administration indicate that (3) Directions—(i) The labeling of all multiple container sizes of sodium orally or rectally administered OTC phosphates oral solution available in drug products containing sodium the marketplace have caused consumer phosphates shall contain the following confusion and appear to have been in- directions in boldface type imme- volved in several consumer deaths. So- diately preceding the dosage informa- dium phosphates oral solution has been tion: ‘‘Do not’’ (‘‘take’’ or ‘‘use’’) marketed in 45-milliliter (mL), 90-mL, ‘‘more unless directed by a doctor. See and 240-mL container sizes. The 45-mL Warnings.’’ and 90-mL container sizes of sodium (ii) For products containing dibasic phosphates oral solution are often rec- sodium phosphate/monobasic sodium ommended and prescribed by physi- phosphate identified in § 334.16(d) mar- cians for bowel cleansing prior to sur- keted as a solution. Adults and chil- gery and diagnostic procedures of the dren 12 years of age and over: Oral dos- colon. Sodium phosphates oral solution age is dibasic sodium phosphate 3.42 to (adult dose 20 mL to 45 mL) is also used 7.56 grams (g) and monobasic sodium as an over-the-counter (OTC) laxative phosphate 9.1 to 20.2 g (20 to 45 mL di- for the relief of occasional constipa- basic sodium phosphate/monobasic so- tion. Accidental overdosing and deaths dium phosphate oral solution) as a sin- have occurred because the 240-mL con- gle daily dose. ‘‘Do not take more than

82

VerDate Mar<15>2010 08:48 May 17, 2010 Jkt 220068 PO 00000 Frm 00092 Fmt 8010 Sfmt 8010 Y:\SGML\220068.XXX 220068 wwoods2 on DSKDVH8Z91PROD with CFR Food and Drug Administration, HHS § 201.309

45 mL (9 teaspoonfuls or 3 tablespoon- beled as an emergency treatment for fuls) in a 24-hour period.’’ Children 10 use in poisonings should be available and 11 years of age: Oral dosage is diba- over the counter has been controver- sic sodium phosphate 1.71 to 3.78 g and sial. monobasic sodium phosphate 4.5 to 10.1 (b) In connection with its study of g (10 to 20 mL dibasic sodium phos- this problem, the Food and Drug Ad- phate/monobasic sodium phosphate ministration has obtained the views of oral solution) as a single daily dose. medical authorities. It is the unani- ‘‘Do not take more than 20 mL (4 tea- mous recommendation of the American spoonfuls) in a 24-hour period.’’ Chil- Academy of Pediatrics, the American dren 5 to 9 years of age: Oral dosage is Association of Poison Control Centers, dibasic sodium phosphate 0.86 to 1.89 g the American Medical Association, and and monobasic sodium phosphate 2.2 to the Medical Advisory Board of the 5.05 g (5 to 10 mL dibasic sodium phos- Food and Drug Administration that ip- phate/monobasic sodium phosphate ecac syrup in 1 fluid ounce containers oral solution) as a single daily dose. be permitted to be sold without pre- ‘‘Do not take more than 10 mL (2 tea- scription so that it will be readily spoonfuls) in a 24-hour period.’’ Chil- available in the household for emer- dren under 5 years of age: ask a doctor. gency treatment of poisonings, under (c) After June 22, 1998, for package medical supervision, and that the drug size limitation and September 18, 1998, be appropriately packaged and labeled for labeling in accord with paragraph for this purpose. (b) of this section, any such OTC drug (c) In view of the above recommenda- product initially introduced or ini- tions, the Commissioner of Food and tially delivered for introduction into Drugs has determined that it is in the interstate commerce, or any such drug interest of the public health for ipecac product that is repackaged or relabeled syrup to be available for sale without after these dates regardless of the date prescription, provided that it is pack- the product was manufactured, ini- aged in a quantity of 1 fluid ounce (30 tially introduced, or initially delivered milliliters), and its label bears, in addi- for introduction into interstate com- tion to other required label informa- merce, that is not in compliance with tion, the following, in a prominent and this section is subject to regulatory ac- conspicuous manner: tion. (1) A statement conspicuously boxed [63 FR 27843, May 21, 1998] and in red letters, to the effect: ‘‘For emergency use to cause vomiting in § 201.308 Ipecac syrup; warnings and poisoning. Before using, call physician, directions for use for over-the- the Poison Control Center, or hospital counter sale. emergency room immediately for ad- (a) It is estimated that each year vice.’’ about 500,000 accidental poisonings (2) A warning to the effect: ‘‘Warn- occur in the United States and result ing—Keep out of reach of children. Do in approximately 1,500 deaths, of which not use in unconscious persons. Ordi- over 400 are children. In the emergency narily, this drug should not be used if treatment of these poisonings, ipecac strychnine, corrosives such as alkalies syrup is considered the emetic of (lye) and strong acids, or petroleum choice. The immediate availability of distillates such as kerosine, gasoline, this drug for use in such situations is coal oil, fuel oil, paint thinner, or critical, since rapid treatment may be cleaning fluid have been ingested.’’ the difference between life and death. (3) Usual dosage: 1 tablespoon (15 mil- The restriction of this drug to prescrip- liliters) in persons over 1 year of age. tion sale limits its availability in emergencies. On the other hand, it is § 201.309 Acetophenetidin (phen- the consensus of informed medical acetin)-containing preparations; opinion that ipecac syrup should be necessary warning statement. used only under medical supervision in (a) In 1961, the Food and Drug Admin- the emergency treatment of istration, pursuant to its statutory re- poisonings. In view of these facts, the sponsibility for the safety and effec- question of whether ipecac syrup la- tiveness of drugs shipped in interstate

83

VerDate Mar<15>2010 08:48 May 17, 2010 Jkt 220068 PO 00000 Frm 00093 Fmt 8010 Sfmt 8010 Y:\SGML\220068.XXX 220068 wwoods2 on DSKDVH8Z91PROD with CFR