201.314—Labeling of drug preparations containing salicylates.

(a) The label of any oral drug preparation intended for sale without prescription and which contains any salicylate ingredient (including aspirin, salicylamide, other salicylates, and combinations) must conspicuously bear, on a clearly contrasting background, the warning statement: “Keep out of reach of children [highlighted in bold type]. In case of overdose, get medical help or contact a Poison Control Center right away,” or “Keep out of reach of children [highlighted in bold type],” except that if the article is an aspirin preparation, it shall bear the first of these warning statements. Such a warning statement is required for compliance with section 502(f)(2) of the Federal Food, Drug, and Cosmetic Act and is intended to guard against accidental poisonings. Safety closures that prevent access to the drug by young children are also recommended to guard against accidental poisonings.

(b) Effervescent preparations and preparations containing para-aminosalicylate as the only salicylate ingredient are exempted from this labeling requirement.

(c) Aspirin tablets sold as such and containing no other active ingredients, except tablets which cannot be readily subdivided into a child's dose because of their coating or size, should always bear dosage directions for each age group down to 3 years of age, with a statement such as “For children under 3 years of age, consult your physician.” It is recommended that:

(1) Aspirin tablets especially made for pediatric use be produced only in 1 1/4 -grain size to reduce the hazard of errors in dosage;

(2) By June 1, 1967, manufacturers and distributors of 1 1/4 -grain size aspirin tablets discontinue the distribution of such tablets in retail containers containing more than 36 tablets, to reduce the hazard of accidental poisoning;

(3) The flavoring of 5-grain aspirin tablets or other “adult aspirin tablets” be discontinued; and

(4) Labeling giving undue emphasis to the pleasant flavor of flavored aspirin tablets be discontinued.

(d) Salicylate preparations other than aspirin tablets sold as such may, at the option of the distributor, be labeled for use by adults only. If their labeling and advertising clearly offer them for administration to adults only.

(e) (1) It is the obligation of the distributor who labels a salicylate preparation for administration to children to make certain that the article is suitable for such use and labeled with adequate directions for use in the age group for which it is offered, but in no case should such an article bear directions for use in children under 3 years of age. If the directions provide for administration to children as young as 3 years of age, the label should bear the statement, “For children under 3 years of age consult your physician.” However, if the directions provide for administration to children only of an age greater than 3 years (for example, the dosage instructions provide for administration of the article to children only down to age 6), the label should bear a statement such as, “For younger children consult your physician.”

(2) A statement such as, “For children under 3 years of age consult your physician” or “For younger children consult your physician” is not required on the label of an article clearly offered for administration to adults only.

(f) If the labeling or advertising of a salicylate preparation offers it for use in arthritis or rheumatism, the label and labeling should clearly state that the beneficial effects claimed are limited to: “For the temporary relief of minor aches and pains of arthritis and rheumatism.” The qualifying phrase “for the temporary relief of minor aches and pains” should appear with the same degree of prominence and conspicuousness as the phrase “arthritis and rheumatism”. The label and labeling should bear in juxtaposition with such directions for use conspicuous warning statements to the effect: “Caution: If pain persists for more than 10 days, or redness is present, or in conditions affecting children under 12 years of age, consult a physician immediately.” The salicylate dosage should not exceed 60 grains in a 24-hour period or 10 grains in a 4-hour period. If the article contains other analgesics, the salicylate dosage should be appropriately reduced.

(g) (1) The label of any drug containing more than 5 percent methyl salicylate (wintergreen oil) should bear a conspicuous warning such as: “Do not use otherwise than as directed.” These drug products must also include the “Keep out of reach of children” warning and the accidental ingestion warning as required in § 330.1(g) of this chapter.

(2) If the preparation is a counterirritant or rubefacient, it should also bear a caution such as, “Caution: Discontinue use if excessive irritation of the skin develops. Avoid getting into the eyes or on mucous membranes.” (See also § 201.303.)

(h) (1) The labeling of orally or rectally administered over-the-counter drug products containing aspirin or nonaspirin salicylates as active ingredients subject to this paragraph is required to prominently bear the following warning: “Reye's syndrome [subheading in bold type]: Children and teenagers who have or are recovering from chicken pox or flu-like symptoms should not use this product. When using this product, if changes in behavior with nausea and vomiting occur, consult a doctor because these symptoms could be an early sign of Reye's syndrome, a rare but serious illness.”

(2) This warning statement shall appear on the immediate container labeling. In cases where the immediate container is not the retail package, the retail package also must bear the warning statement. In addition, the warning statement shall appear on any labeling that contains warnings and, in such cases, the warning statement shall be the first warning statement under the heading “Warnings.”

(3) Over-the-counter drug products subject to this paragraph and labeled solely for use by children (pediatric products) shall not recommend the product for use in treating flu or chicken pox.

(4) Any product subject to paragraphs (h)(1), (h)(2), and (h)(3) of this section that is not labeled as required by these paragraphs and that is initially introduced or initially delivered for introduction into interstate commerce after the following dates is misbranded under sections 201(n) and 502(a) and (f) of the Federal Food, Drug, and Cosmetic Act.

(i) Compliance by October 18, 2004, for OTC drug products containing aspirin and nonaspirin salicylates as an active ingredient and marketed under a new drug application or abbreviated new drug application.

(ii) Compliance by April 19, 2004, for OTC antidiarrheal and overindulgence drug products that contain bismuth subsalicylate as an active ingredient and have annual sales greater than $25,000.

(iii) Compliance by April 18, 2005, for OTC antidiarrheal and overindulgence drug products that contain bismuth subsalicylate as an active ingredient and have annual sales less than $25,000.

(iv) Compliance dates for all other OTC drug products containing aspirin and nonaspirin salicylates as an active ingredient and marketed under an OTC drug monograph (for internal analgesic, antipyretic, and antirheumatic drug products, or for menstrual drug products) will be established when the final monographs for those products are published in a future issue of the Federal Register. In the interim, these products should continue to be labeled with the previous Reye's syndrome warning that appears in paragraph (h)(1) of this section.

Code of Federal Regulations

[40 FR 13998, Mar. 27, 1985, as amended at 51 FR 8182, Mar. 7, 1986; 53 FR 21637, June 9, 1988; 53 FR 24830, June 30, 1988; 64 FR 13291, Mar. 17, 1999; 65 FR 8, Jan. 3, 2000; 68 FR 18869, Apr. 17, 2003]

CFR

201.314—Labeling of drug preparations containing salicylates.

Code of Federal Regulations