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ASPIRIN IN CHEWING GUM BASE IS CATEGORY III AS ANESTHETIC/ANALGESIC FOR ORAL CAVITY; PERBORATE FOR DEBRIDING IS SWITCHED BY FDA TO CATEGORY I INGREDIENT

Executive Summary

Additional efficacy data is needed on aspirin in a chewing base as an anesthetic or analgesic agent for oral health care, FDA concluded in the Tentative Final Monograph (TFM) for OTC Oral Health Care Drug Products. Aspirin previously had been recommended as a Category I (safe and effective) ingredient by the Oral Cavity Panel. Despite the panel's recommendation for Category I, a minority of panel members had questioned both the safety and efficacy of topically applied aspirin. FDA explained that it is reclassifying the agent because of the panel's disagreement as well as new study results which bring into question the efficacy of topical aspirin. "The agency believes that because there was a divided recommendation by the Oral Cavity Panel, because two other panels [the Topical Analgesic Panel and the Internal Analgesic Panel] concluded that aspirin has no known local analgesic effect, and because [published studies] present conflicting data, a reasonable question exists regarding the ability of aspirin to exert a topical analgesic effect on the oral mucosa," FDA said. The agency suggests that companies check on efficacy protocols before beginning studies. "Testing using protocols similar to those employed in a study" published in 1981 by J. Andriani, S. Minokaden, and M. Naraghi, were recommended by FDA. FDA, however, does not challenge the status of topical aspirin as a safe ingredient for use in the oral cavity. "With regard to the safety of aspirin for topical use in the oral cavity, the agency accepts the conclusion of the majority of the panel and agrees with the comments that aspirin in a chewing gum base is safe for topical use on the mucous membranes of the mouth and throat when labeled with adequate warnings," the TFM states. Should aspirin be included in the final monograph, FDA proposes that the products carry a warning statement: "Do not use if you have a bleeding problem, if you are taking a prescription drug for anticoagulation (thinning the blood), if your mouth is highly irritated or ulcerated, or for at least 7 days after surgery in the mouth or throat except under the advice and supervision of a dentist or doctor." Sodium perborate monohydrate, classified as a Category II ingredient by the panel, was moved to Category I status in the TFM (see chart next page for a comparison of panel and FDA classifications of all ingredients). FDA explained that it was moving the ingredient to a "safe and effective" classification based on its status in the OTC TFM for oral mucosal injury drug products. "The agency is incorporating part of the rulemaking on OTC oral mucosal injury drug products into the sections of this [TFM] pertaining to debriding agents," FDA explained. "Therefore, the agency is proposing a Category I classification for sodium perborate monohydrate as a debriding agent/oral wound cleanser." Sugars and sorbitol are listed as Category III (more study needed) agents for use as active oral health care demulcent ingredients. The panel had not reviewed the two ingredients. FDA noted that it added sugars (sucrose, dextrose, fructose, and dextrins) and sorbitol based on a comment submitted to the agency. The comment included a double-blind study comparing the effectiveness of a candy-based, 2.4 mg hexylresorcinol lozenge with two candy-based placebo lozenges, one flavored. FDA's "review of the results showed that there was some immediate subjective relief of sore throat pain in all groups tested and that the degree of relief was virtually the same in all three groups. At five minutes, the relief of sore throat pain provided by the hexylresorcinol lozenge was significantly better than the relief provided by the candy-based control lozenges," the TFM states. "Nevertheless," FDA added, the control lozenges provided some sore throat relief." FDA explained that it "agrees with the comment that sugars and sorbitol may have demulcent activity when used in lozenge or syrup form," but that adequately designed and controlled studies are necessary to assess efficacy. The submitted study, FDA said, "does not demonstrate the effectiveness of sugar as a demulcent in lozenges because the ingredients used to formulate the candy-based lozenges are not identified or quantitated and because both unmedicated lozenges were candy-based." The comment also submitted two studies evaluating the antitussive effectiveness of sugar and sorbitol through a citric acid aerosol challenge-cough induction technique. Those studies, FDA said, "do not clearly demonstrate the demulcent effectiveness of sugars or sorbitol because the subjects studied did not have a sore mouth and throat." Therefore, FDA advised, "studies conducted to demonstrate the demulcent effect of ingredients must be conducted in the correct target population, i.e., subjects with a sore mouth or throat." FDA deferred a decision on oral health care expectorant and decongestant ingredients for future monographs on cough-cold products. The ingredients will be discussed in the OTC nasal decongestant and OTC expectorant sections of the monograph, respectively. As proposed by the Oral Cavity Panel, systemic relief of sore throat pain is not considered in the oral health care TFM, but will be addressed in the rulemaking for OTC internal analgesic, antipyretic, and antirheumatic drug products. The TFM also defers consideration of the combination of oral wound cleansers and antiseptics. The combinations will be reviewed in the antimicrobial segment of the rulemaking for OTC oral health care products. In line with its combination drug policy, FDA rejected the panel's recommendation that a combination of oral health care ingredients from the same category demonstrate improved efficacy or safety when compared to the single agents. The TFM requires only that combinations from the same therapeutic category which have different mechanisms of action demonstrate an advantage over individual ingredients. The TFM proposes two combination products in Category I: benzocaine with phenol, and benzocaine with menthol. The TFM specifically asks for comments on how to distinguish menthol as an active ingredient, as well as the minimum amount of the ingredient needed to achieve a flavoring effect and a therapeutic effect. Category III combinations in the monograph include: menthol and benzyl alcohol, phenol, or salicyl alcohol; an anesthetic/analgesic and an internal analgesic; and an anesthetic analgesic, an internal analgesic, and a demulcent. The agency proposed a Category II classification for a product combining a debriding agent/oral wound cleanser and demulcent. Chart omitted.
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