§ 201.307 21 CFR Ch. I (4–1–12 Edition)

(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 tainer was mistakenly used instead of 45 mL (9 teaspoonfuls or 3 tablespoon- the 45-mL or 90-mL container. The fuls) in a 24-hour period.’’ Children 10 Food and Drug Administration is lim- and 11 years of age: Oral dosage is diba- iting the amount of sodium phosphates sic sodium phosphate 1.71 to 3.78 g and oral solution to not more than 90 mL (3 monobasic sodium phosphate 4.5 to 10.1 ounces (oz)) per OTC container because g (10 to 20 mL dibasic sodium phos- of the serious health risks associated phate/monobasic sodium phosphate with the ingestion of larger than in- oral solution) as a single daily dose. tended doses of this product. Further, ‘‘Do not take more than 20 mL (4 tea- because an overdose of either oral or spoonfuls) in a 24-hour period.’’ Chil- rectal enema sodium phosphates can dren 5 to 9 years of age: Oral dosage is cause an electrolyte imbalance, addi- dibasic sodium phosphate 0.86 to 1.89 g tional warning and direction state- and monobasic sodium phosphate 2.2 to ments are required for the safe use of 5.05 g (5 to 10 mL dibasic sodium phos- any OTC laxative drug product con- phate/monobasic sodium phosphate taining sodium phosphates. oral solution) as a single daily dose.

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‘‘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- counter sale. the Poison Control Center, or hospital 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 choice. The immediate availability of (lye) and strong acids, or petroleum this drug for use in such situations is distillates such as kerosine, gasoline, critical, since rapid treatment may be coal oil, fuel oil, paint thinner, or the difference between life and death. cleaning fluid have been ingested.’’ The restriction of this drug to prescrip- (3) Usual dosage: 1 tablespoon (15 mil- tion sale limits its availability in liliters) in persons over 1 year of age. emergencies. On the other hand, it is the consensus of informed medical § 201.309 Acetophenetidin (phen- acetin)-containing preparations; opinion that ipecac syrup should be necessary warning statement. used only under medical supervision in the emergency treatment of (a) In 1961, the Food and Drug Admin- poisonings. In view of these facts, the istration, pursuant to its statutory re- question of whether ipecac syrup la- sponsibility for the safety and effec- beled as an emergency treatment for tiveness of drugs shipped in interstate use in poisonings should be available commerce, began an active investiga- over the counter has been controver- tion of reports of possible toxic effects sial. and renal damage due to misuse of the (b) In connection with its study of drug acetophenetidin. This study led to this problem, the Food and Drug Ad- the decision that there was probable ministration has obtained the views of cause to conclude that misuse and pro- medical authorities. It is the unani- longed use of the drug were in fact re- mous recommendation of the American sponsible for kidney lesions and dis- Academy of Pediatrics, the American ease. The Commissioner of Food and Association of Poison Control Centers, Drugs, in December 1963, appointed an the American Medical Association, and ad hoc Advisory Committee of Inquiry the Medical Advisory Board of the on Possible Nephrotoxicity Associated Food and Drug Administration that ip- With the Abuse of Acetophenetidin ecac syrup in 1 fluid ounce containers (Phenacetin)-Containing Preparations. be permitted to be sold without pre- This committee, composed of scientists

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