WHITEHALL COAL TAR/MENTHOL SHAMPOO (DENOREX) IS MORE EFFECTIVE THAN COAL TAR ALONE

WHITEHALL COAL TAR/MENTHOL SHAMPOO (DENOREX) IS MORE EFFECTIVE THAN COAL TAR ALONE for relieving itch associated with dandruff, according to the results of a clinical trial submitted to FDA on March 23 in support of reopening the dandruff final monograph. Based on a 300-person, three-armed study comparing 9% coal tar/1.5% menthol shampoo, 9% coal tar shampoo and 1.5% menthol shampoo, Whitehall stated that the combination and "menthol alone were significantly superior to coal tar alone in both control of [dandruff] itch and relief of itch at almost every point" in the one-hour post-treatment follow-up. Coal tar and menthol are the active ingredients in Whitehall's Denorex dandruff shampoo. While coal tar is Category I for treating flaking, menthol was placed in Category II for treating scalp itching in the dandruff final monograph published in December 1991. The latest study (WM-613), conducted by Peter Winters, MD, Indianapolis, was submitted in support of a 1987 Whitehall study. The single-dose, double-blind, randomized parallel study was "designed to address" March 1991 comments from FDA on the original protocol by including "a menthol-only arm and appropriate blinding procedures," Whitehall noted in its letter to the agency. FDA accepted the study protocol in a January 1992 letter to Whitehall, sent one month after the December 1991 publication of the final rule on OTC dandruff, seborrheic dermatitis and psoriasis products. The study, which enrolled 300 subjects with moderate to severe dandruff and "at least a moderately intense degree of itching," was designed to measure the safety and efficacy of menthol as an antipruritic agent in dandruff shampoo. Treatment consisted of a one-and-a-half minute shampoo with either 9% coal tar and 1.5% menthol in combination or as single ingredients. For one hour after the shampoo, the subjects were asked to rate the antipruritic activity of whatever treatment they received at intervals of five, 15, 30 and 60 minutes using a "control of itch" visual analog scale (0 = does not itch, 100 = itches a lot) and a six-category "relief of itch" scale. The study found that "the control of itch improved over time in all three groups." However, the combination shampoo "was shown to be statistically superior to coal tar alone at five, 15 and 30 minutes" and "showed numerical, but not statistical, superiority to coal tar at 60 minutes. The menthol shampoo was statistically superior to coal tar at every time point," the study states. "It is evident from these results that the combination of menthol and coal tar provided additional itch control and significantly greater relief of itch over coal tar alone in the immediate post-treatment period," the study concludes. Whitehall declared that "the data presented here confirm the findings of the previous study." In earlier correspondence with the company, FDA questioned the acceptability of the 1.5% menthol level in the Denorex formulation due to concerns about safety. Whitehall stated in the letter to the agency that the safety profile in the study "supports our contention that given the dilution with water during shampooing the actual concentration of menthol coming in contact with the scalp is much less than 1.5% and would therefore be in the concentration acceptable for an analgesic/anesthetic/antipruritic." The single-use study found only one adverse reaction in the coal tar group -- alopecia -- that was later determined to probably result from "a history of chemically based hair processing treatments," Whitehall noted. In denying the combination of coal tar and menthol Category I status in the final monograph, FDA determined that the submitted data did "not demonstrate that the combination offers any advantage."