Cetylpyridinium chloride mouthwash ingredient voted Category I for safety, efficacy.

CETYLPYRIDINIUM CHLORIDE MOUTHWASH INGREDIENT DEEMED CATEGORY I for plaque and gingivitis treatment by FDA's Dental Products Panel Plaque Subcommittee at its May 8-9 meeting in Bethesda, Md. The eight-member subcommittee unanimously voted that the ingredient, contained in Procter & Gamble's Scope, J.B. Williams' Cepacol and other products, including Plus+White Anti-Stain Oral Rinse (CCA Industries), Swish (Unico) and Tech 2000 (Care-Tech Labs), should be classified as safe and effective for the treatment of both plaque and gingivitis.

Procter & Gamble presented safety and efficacy data in support of the use of CPC at the subcommittee's Dec. 16-17 meeting ("The Tan Sheet" Dec. 23, 1996, pp. 1-8). However, the subcommittee opted to defer voting on the ingredient until the company showed "clinical relevance data" for CPC, similar to what had been shown during P&G's December presentation for stannous fluoride. The committee requested this type of analysis for all ingredients under consideration.

P&G Associate Director and Senior Researcher Matthew Dayle, PhD, presented data at the May 8 meeting showing that over 35% of users of CPC showed a 50% reduction in gingival bleeding sites after six months of using products containing concentrations of CPC between .05%-.1%.

Between 25%-30% of CPC users experienced a 25% reduction in bleeding sites after six months, slightly less than the number of controls that experienced benefits of that magnitude. Between 10%-15% of CPC users had no change, with a slightly lower number actually worsening while receiving treatment. Between 25%-30% of controls experienced a 25% worsening of bleeding sites over the course of the trial period.

P&G also compared the improvements experienced with CPC therapy with other oral care practices: users of CPC in two P&G studies averaged a 19.5% improvement in gingival index and a 26.5% improvement in bleeding; increasing brushing frequency from once to twice a day causes 17.6% and 27.7% improvements in the two measurements, respectively; and increasing dental visits from once to twice a year effects improvements in gingival index and improvement in bleeding of 19.3% and 36.5%. Introducing dental floss into a "floss-less" oral hygiene regimen, however, produces the greatest improvements: 32.9% and 51.4%, respectively, in gingival index and bleeding.

Overall, P&G found that users of CPC across four studies were about three times as likely to experience a 33% reduction in the number of bleeding sites as their control group counterparts. The odds are about the same at three to four months of use and at six months of use.

Dennis Houston, a representative from Cepacol maker J.B. Williams, noted that in P&G's previous presentation to the committee on cetylpyridinium chloride, the firm provided "information that said it is possible to formulate products that are not active that contain CPC" and "introduced several methods...for demonstrating how to insure effectiveness." The consultant queried whether P&G would propose, in recommending Category I status, "that there be additional criteria for CPC to meet in order to meet monograph requirements."

At the December meeting, P&G recommended that "prudence" be exercised during formulation; surfactants or anionic material in the product can de-activate CPC, the company said.

At the subcommittee's August 1995 meeting, Chairman Robert Genco, PhD/DDS, SUNY-Buffalo, noted that data presented by P&G showing gingivitis efficacy did not agree with data presented by Marion Merrell Dow, then-owners of Cepacol, that showed no efficacy of the ingredient against gingivitis ("The Tan Sheet" Aug. 21, 1995, pp. 11-12). Both companies presented data demonstrating plaque efficacy for CPC. However, at the subcommittee's meeting the following June, P&G said the discrepancy was due to differences in formulation between the two products ("The Tan Sheet" June 17, 1996, p. 6).

At the most recent meeting, P&G said the discrepancy is due to "chemically available and biologically effective" levels of CPC in the product -- not, P&G's Doyle said, the "nominal level" of CPC. Two assays P&G conducted on its CPC formulation confirmed both chemical availability and biological effectiveness of its product, Doyle added.

"Are you suggesting...that monograph products now each have to be clinically studied," Houston continued. P&G's Doyle declined to make a "suggestion," adding: "That's part of the deliberations that this subcommittee has before them."

P&G noted that there is little dose-response shown in its studies of CPC. "We see relatively similar efficacy across the dose range of .05% to .1%," Doyle noted. CPC, "for a variety of outcome variables, has a rather steep pharmacologic curve, and it appears we're on the plateau," he said.