PART 346—ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371. Source: 55 FR 31779, Aug. 3, 1990, unless otherwise noted. Subpart A—General Provisions § 346.1 Scope. (a) An over-the-counter anorectal drug product in a form suitable for external (topical) or intrarectal (rectal) administration is generally recognized as safe and effective and is not misbranded if it meets each condition in this part and each general condition established in § 330.1 of this chapter. (b) References in this part to regulatory sections of the Code of Federal Regulations are to chapter I of title 212 unless otherwise noted. § 346.3 Definitions. As used in this part: (a) Analgesic, anesthetic drug. (b) Anorectal drug. (c) Antipruritic drug. (d) Astringent drug. (e) External use. (f) Intrarectal use. (g) Keratolytic drug. (h) Local anesthetic drug. (i) Protectant drug. (j) Vasoconstrictor. Subpart B—Active Ingredients § 346.10 Local anesthetic active ingredients. The active ingredient of the product consists of any of the following when used in the concentration or within the concentration range established for each ingredient: (a) Benzocaine 5 to 20 percent. (b) Benzyl alcohol 1 to 4 percent. (c) Dibucaine 0.25 to 1 percent. (d) Dibucaine hydrochloride 0.25 to 1 percent. (e) Dyclonine hydrochloride 0.5 to 1 percent. (f) Lidocaine 2 to 5 percent. (g) Pramoxine hydrochloride 1 percent. (h) Tetracaine 0.5 to 1 percent. (i) Tetracaine hydrochloride 0.5 to 1 percent. § 346.12 Vasoconstrictor active ingredients. The active ingredient of the product consists of any of the following when used in the concentration or within the concentration range established for each ingredient. (a) Ephedrine sulfate 0.1 to 1.25 percent. (b) Epinephrine 0.005 to 0.01 percent. (c) Epinephrine hydrochloride 0.005 to 0.01 percent. (d) Phenylephrine hydrochloride 0.25 percent. § 346.14 Protectant active ingredients. (a) The following active ingredients may be used as the sole protectant active ingredient in a product if the ingredient as identified constitutes 50 percent or more by weight of the final product. In addition, the following active ingredients may be used in concentrations of less than 50 percent by weight only when used in combinations in accordance with § 346.22 (a), (b), or (n). (1) Aluminum hydroxide gel. (2) Cocoa butter. (3) Glycerin in a 20- to 45-percent (weight/weight) aqueous solution so that the final product contains not less than 10 and not more than 45 percent glycerin (weight/weight). Any combination product containing glycerin must contain at least this minimum amount of glycerin. (4) Hard fat. (5) Kaolin. (6) Lanolin. (7) Mineral oil. (8) Petrolatum. (9) Topical starch. (10) White petrolatum. (b) The following active ingredients may not be used as a sole protectant ingredient but may be used in combination with one, two, or three other protectant active ingredients in accordance with § 346.22 (a), (b), (n), and (o) and with the following limitations: (1) Calamine not to exceed 25 percent by weight per dosage unit (based on the zinc oxide content of calamine). (2) Cod liver oil, provided that the product is labeled so that the amount of the product that is used in a 24-hour period represents a quantity that provides 10,000 U.S.P. units of vitamin A and 400 U.S.P. units of cholecalciferol. (3) Shark liver oil, provided that the product is labeled so that the amount of the product that is used in a 24-hour period represents a quantity that provides 10,000 U.S.P. units of vitamin A and 400 U.S.P. units of cholecalciferol. (4) Zinc oxide not to exceed 25 percent by weight per dosage unit. § 346.16 Analgesic, anesthetic, and antipruritic active ingredients. The active ingredient of the product consists of any of the following when used within the concentration range established for each ingredient: (a) Camphor 0.1 to 3 percent. (b) Juniper tar 1 to 5 percent. (c) Menthol 0.1 to 1 percent. § 346.18 Astringent active ingredients. The active ingredient of the product consists of any of the following when used within the concentration range established for each ingredient: (a) Calamine, within a concentration range of 5 to 25 percent by weight per dosage unit (based on the zinc oxide content of calamine). (b) Witch hazel, 10 to 50 percent. (c) Zinc oxide, within a concentration range of 5 to 25 percent by weight per dosage unit. [55 FR 31779, Aug. 3, 1990, as amended at 59 FR 28767, June 3, 1994] § 346.20 Keratolytic active ingredients. The active ingredient of the product consists of any of the following when used within the concentration range established for each ingredient: (a) Alcloxa 0.2 to 2 percent. (b) Resorcinol 1 to 3 percent. § 346.22 Permitted combinations of anorectal active ingredients. (a) Any two, three, or four protectants identified in § 346.14(a) may be combined, except aluminum hydroxide gel in § 346.14(a)(1) and kaolin in § 346.14(a)(5) may not be combined with any ingredient in § 346.14(a) (2), (4), (6), (7), (8) and (10), and (b) (2) and (3), provided that the combined percentage by weight of all protectants in the combination is at least 50 percent of the final product (e.g., 1 gram of a 2-gram dosage unit). Any protectant ingredient included in the combination must be present at a level that contributes at least 12.5 percent by weight (e.g., 0.25 gram of a 2-gram dosage unit), except cod liver oil and shark liver oil. If an ingredient in § 346.14(b) is included in the combination, it must not exceed the concentration limit specified in § 346.14(b). (b) Any single anorectal ingredient identified in § 346.10, 346.12, 346.16, 346.18, or 346.20 may be combined with up to four protectants in accordance with paragraph (a) of this section. (c) Any single local anesthetic identified in § 346.10 may be combined with any single vasoconstrictor identified in § 346.12. (d) Any single local anesthetic identified in § 346.10 may be combined with any single astringent identified in § 346.18. (e) Any single local anesthetic identified in § 346.10 may be combined with any single keratolytic identified in § 346.20. (f) Any single vasoconstrictor identified in § 346.12 may be combined with any single astringent identified in § 346.18. (g) Any single analgesic, anesthetic, and antipruritic identified in § 346.16 may be combined with any single astringent identified in § 346.18. (h) Any single analgesic, anesthetic, and antipruritic identified in § 346.16 may be combined with any single keratolytic identified in § 346.20. (i) Any single astringent identified in § 346.18 may be combined with any single keratolytic identified in § 346.20. (j) Any single local anesthetic identified in § 346.10 may be combined with any single vasoconstrictor identified in § 346.12 and with any single astringent identified in § 346.18. (k) Any single local anesthetic identified in § 346.10 may be combined with any single astringent identified in § 346.18 and with any single keratolytic identified in § 346.20. (l) Any single vasoconstrictor identified in § 346.12 may be combined with any single analgesic, anesthetic, and antipruritic identified in § 346.16 and with any single astringent identified in § 346.18. (m) Any single analgesic, anesthetic, and antipruritic identified in § 346.16 may be combined with any single astringent identified in § 346.18 and with any single keratolytic identified in § 346.20. (n) Any combination of ingredients listed in paragraphs (c) through (m) of this section may be combined with up to four protectants in accordance with paragraph (a) of this section. (o) Any product containing calamine for use as a protectant and/or as an astringent and/or containing zinc oxide for use as a protectant and/or as an astringent may not have a total weight of zinc oxide exceeding 25 percent by weight per dosage unit. Subpart C—Labeling § 346.50 Labeling of anorectal drug products. The labeling of the product contains the following information for anorectal ingredients identified in §§ 346.10, 346.12, 346.14, 346.16, 346.18, and 346.20, and for combinations of anorectal ingredients identified in § 346.22. Unless otherwise specified, the labeling in this subpart is applicable to anorectal drug products for both external and intrarectal use. (a) Statement of identity. (b) Indications. (1) (“For the temporary relief of,” “Gives temporary relief of,” or “Helps relieve the”) (As an option, select one or both of the following: “local” or “anorectal”) [select one or more of the following: “discomfort,” “itching,” or “itching and discomfort,” followed by: “in the perianal area” or “associated with” (select one or more of the following: “hemorrhoids,” “anorectal disorders,” “inflamed hemorrhoidal tissues,” “anorectal inflammation,” “hemorrhoidal tissues,” or “piles (hemorrhoids).”)] (2) Additional indications. (i) For products for external use only containing any ingredient identified in § 346.10. (ii) For products containing epinephrine or epinephrine hydrochloride identified in § 346.12 (b) and (c) for external use only, and for products containing ephedrine sulfate or phenylephrine hydrochloride identified in § 346.12 (a) and (d). (A) “Temporarily reduces the swelling associated with” (select one of the following: “irritated hemorrhoidal tissue and other anorectal disorders” or “irritation in hemorrhoids and other anorectal disorders”). (B) “Temporarily shrinks hemorrhoidal tissue.” (iii) For products for external use only containing glycerin identified in § 346.14(a)(3) and for products for external and/or intrarectal use containing any protectant identified in § 346.14(a) (2), (4), (6) through (10), and (b) (1) through (4). (A) “Temporarily forms a protective coating over inflamed tissues to help prevent drying of tissues.” (B) “Temporarily protects irritated areas.” (C) “Temporarily relieves burning.” (D) “Provides temporary relief from skin irritations.” (E) “Temporarily provides a coating for relief of anorectal discomforts.” (F) “Temporarily protects the inflamed, irritated anorectal surface” (select one of the following: “to help make bowel movements less painful” or “from irritation and abrasion during bowel movement”). (G) “Temporarily protects inflamed perianal skin.” (H) “Temporarily relieves the symptoms of perianal skin irritation.” (iv) For products containing aluminum hydroxide gel identified in § 346.14(a)(1) and for products containing kaolin identified in § 346.14(a)(5). (v) For products for external use only containing any analgesic, anesthetic, and antipruritic identified in § 346.16. (B) “Can help distract from pain.” (C) “May provide a cooling sensation.” (vi) For products for external use only containing witch hazel identified in § 346.18(b), and for products for external use and/or intrarectal use containing calamine or zinc oxide identified in § 346.18 (a) and (c). (A) “Aids in protecting irritated anorectal areas.” (B) “Temporary relief of” (select one or both of the following: “irritation” or “burning”). (vii) For products for external use only containing any ingredient identified in § 346.20. (c) Warnings. (1) “If condition worsens or does not improve within 7 days, consult a doctor.” (2) “Do not exceed the recommended daily dosage unless directed by a doctor.” (3) “In case of bleeding, consult a doctor promptly.” (4) For products for external use only. (5) For products for intrarectal use to be used with a special applicator such as a pile pipe or other mechanical device. (6) For products for external use only containing any local anesthetic identified in § 346.10, menthol identified in § 346.16(c), or resorcinol identified in § 346.20(b). (7) For products containing any vasoconstrictor identified in § 346.12. (ii) “Ask a doctor or pharmacist before use if you are [bullet] 1 1 (iii) For products containing ephedrine sulfate identified in § 346.12(a). (8) For products containing aluminum hydroxide gel identified in § 346.14(a)(1) and for products containing kaolin identified in § 346.14(a)(5). (9) For products for external use only containing resorcinol identified in § 346.20(b). (d) Directions. (1) “ Adults: (2) For products for external use only. (3) For products for external use that are pads containing anorectal ingredients. (4) For products for intrarectal use that are wrapped suppositories. (5) For products for intrarectal use that are to be used with a special applicator such as a pile pipe or other mechanical device. (6) For products for external use only containing any of the local anesthetics identified in § 346.10; analgesics, anesthetics, and antipruritics identified in § 346.16; or alcloxa or resorcinol identified in § 346.20. (i) For products for external use only containing dibucaine or dibucaine hydrochloride identified in § 346.10 (c) and (d). (ii) For products for external use only containing pramoxine hydrochloride identified in § 346.10(g). (7) For products containing vasoconstrictors identified in § 346.12. (8) For products for external use only containing glycerin identified in § 346.14(a)(3) or witch hazel identified in § 346.18(b), and for products for external and/or intrarectal use containing any protectant identified in § 346.14(a)(1), (2), (4), (5), (6), (7), and (9), and (b)(1), (2), (3), and (4), or any astringent identified in § 346.18(a) and (c). (9) For products containing petrolatum or white petrolatum identified in § 346.14(a)(8) and (10). (e) The word “physician” may be substituted for the word “doctor” in any of the labeling statements in this section. [55 FR 31779, Aug. 3, 1990, as amended at 59 FR 28767, June 3, 1994; 64 FR 13295, Mar. 17, 1999] § 346.52 Labeling of permitted combinations of anorectal active ingredients. Indications, warnings, and directions for use, respectively, applicable to each ingredient in the product may be combined to eliminate duplicative words or phrases so that the resulting information is clear and understandable. (a) Statement of identity. (b) Indications. (c) Warnings. (d) Directions.