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Executive Summary

FDA's proposed final rule for OTC anorectal products, published in the Aug. 3 Federal Register, designates 33 ingredients as safe and effective for relief of symptoms of hemorrhoids and other rectal conditions. The final rule excludes 30 ingredients for lack of evidence of safety and efficacy (see box, p. 15). FDA said it not yet ready to make a final determination on the status of live yeast cell derivative, the active ingredient in American Home Products' Preparation H and Wyanoids suppositories. FDA listed as Category I (safe and effective): alcloxa, aluminum hydroxide gel, benzocaine, benzyl alcohol, calamine, camphor, cocoa butter, cod liver oil, dibucaine, dibucaine hydrochloride, dyclonine hydrochloride, ephedrine sulfate, epinephrine and epinephrine hydrochloride, glycerin, hammamelis water (NF X1), hard fat, juniper tar, kaolin, lanolin, lidocaine, menthol, mineral oil, petrolatum, phenylephrine hydrochloride, pramoxine hydrochloride, resorcinol, shark liver oil, tetracaine, tetracaine hydrochloride, topical starch, white petrolatum and zinc oxide. The only addition to Category I from the Tentative Final Monograph published in August, 1988, is hard fat (cocoa butter substitutes, hydrogenated coco-glycerides, and hydrogenated palm kernel glycerides). Among the ingredients excluded from the final anorectal monograph as unsafe or ineffective are peruvian balsam and bismuth subgallate (two ingredients in Parke-Davis' Anusol suppositories). Products that contain any of the 30 excluded ingredients will have twelve months from the date of the notice to reformulate. Live yeast cell derivative (LYCD) as a wound healing agent is one of two ingredients still under review by FDA, the agency noted. Whitehall submitted two clinical studies a year ago in an attempt to demonstrate efficacy for LYCD ("The Pink Sheet" Aug. 28, 1989, T&G-11), which was Category III in the TFM. Products containing LYCD can remain on the market at this time and are not affected by the current final rule. The second held-over decision is on hydrocortisone as a combination with other OTC ingredients, such as pramoxine; no OTC anorectals with such combinations are currently on the market, FDA notes, but several manufacturers are interested in pursuing the indication. The agency will amend the final rule once its review of the two ingredients is completed. Regarding labelling, FDA notes that ingredients specifically used for relief of pain are approved for external use only; all ingredients for those indications will have to bear a warning against use inside the rectum itself, FDA specifies. Ingredients that have been approved for shrinking hemorroidal tissue, meanwhile, must bear the warning: "Do not use this product if you have heart disease, high blood pressure, thyroid disease, diabetes or difficulty in urination due to enlargement of the prostate gland unless directed by a doctor." Certain other ingredients must also be accompanied by specific warnings. The anesthetic ingredients, plus menthol and resorcinol, must carry a warning that certain individuals are allergic to those ingredients. Products containing ephedrine sulfate, an ingredient in Bristol-Myers' Pazo suppositories and ointment, must warn "some users of this product may experience nervousness, tremor, sleeplessness, nausea and loss of appetite. If these symptoms persist...consult your doctor." Under the notice's indications section, specific claims that may be used with certain ingredients are also spelled out. Products containing epinephrine, epinephrine HCl, ephedrine, or phenylephrine can state "temporarily shrinks hemorrhoidal tissue." Skin protectant-containing products and products containing the astringents calamine, hamamelis water, and zinc oxide can claim "temporarily protects irritated areas...temporarily relieves burning" and similar statements. Products containing aluminum hydroxide gel can claim "for the temporary relief of itching associated with most anorectal conditions." Anesthetic, analgesic and antipruritic-containing products can state "temporary relief of pain/burning...can help distract from pain...may help provide a cooling sensation." The final rule contains one minor alteration of the TFM's ruling that any of the skin protectants can be combined with each other. FDA has now determined that aluminum hydroxide gel and kaoln should not be combined with any of the "greasy" skin protectants (cocoa butter, cod liver oil, hard fat, lanolin, mineral oil, petrolatum, shark liver oil and white petrolatum) because they interfere with the greasy ingredients' adherence to skin. The proposal also outlines all other permissible combinations of ingredients, which remain the same as in the TFM. Among the combinations allowed by the monograph are: any single monograph ingredient in combination with up to four skin protectants; and any single anesthetic ingredient together with any single vasoconstrictor. Any single anesthetic can be in combination with any single vasoconstrictor. Other possible combos are any single anesthetic and any single astringent; any one anesthetic and any single keratolytic; or any single vasoconstrictor together with any single astringent. Other allowable mixtures are: any antipruritic combined with any single keratolytic; or, any single astringent with any single keratolytic. Each single anesthetic can be put together with any single vasoconstrictor plus any single astringent. Any anesthetic plus any one astringent and any one keratolytic is allowable. Additionally, any single vasoconstrictor may be combined with any one analgesic, any one antipruritic, and any one astringent. Any particular approved antipruritic may be added to any single astringent plus any single keratolytic. FDA OTC Drug Evaluation Director William Gilbertson noted in an agency release on the final rule that at least one of the approved ingredients was already present in "virtually every major nonprescription rectal product" currently sold in the U.S. He estimated the size of the U.S. OTC hemorrhoid market at $150 mil.

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