ATTAPULGITE ANTIDIARRHEAL EFFICACY IS UNPROVEN IN ADULTS

ATTAPULGITE ANTIDIARRHEAL EFFICACY IS UNPROVEN IN ADULTS, a joint session of FDA's OTC Drugs and Gastrointestinal Drugs Advisory Committees decided by a 14-1 vote (with one abstention) on April 9. The joint committee found that the data from four attapulgite studies were inconclusive to support the ingredient's efficacy for treating adult cases of simple acute diarrhea. The joint committee also agreed, with no opposition, that attapulgite's safety and effectiveness in children has not been established. OTC Advisory Committee Chairman Randy Juhl, PhD, University of Pittsburgh, noted that the committee was "not impressed with the data on attapulgite." Two of the trials considered by the panel lacked a placebo control and a third used a lactose-based placebo. Juhl suggested that "there are better ways to study this malady than some of these studies." The joint committee voted 8-6 that kaolin's effectiveness as an OTC antidiarrheal in adults had been established in two placebo-control studies (#303 and #302). The committee concluded that a kaolin's mean 10% effect in shortening duration of acute diarrhea combined with a stool hardening effect represented symptomatic relief. The committee heard presentations on four kaolin studies. Three of the studies, Portnoy et al., #295 and #303, showed statistically significant increased stool formation in the kaolin group. The last study presented to the committee, Alestig et al., showed no effect on either stool frequency or stool consistency. However, FDA Gastrointestinal and Coagulation Drug Products Division Director Stephen Fredd, MD, suggested that increased stool formation could be considered a cosmetic endpoint. Office of OTC Drug Evaluation Director-designate Michael Weintraub, MD, pointed out that "the number of patients recovering from diarrhea . . . [without] symptoms . . . may be the single most relevant thing." Of the attapulgite studies considered by the joint committee, de Sola Pool et al., which contained no control group, found no statistical significance between attapulgite and loperamide. Committee member Marcus Reidenberg, MD, Cornell Medical Center, suggested that the second trial, DuPont et al. -- another loperamide comparison trial without a placebo control -- was "just uninterpretable." Pfizer's 1974 study, a placebo-control trial with attapulgite, leaned toward the drug group in terms of effect on number of cramps, number of bowel movements, and the subjects' evaluation of effectiveness. However, the panel was skeptical of the results given that patients were not permitted to fill out their own data forms. Because Pfizer's 1980 study compared attapulgite/pectin to placebo, FDA decided it cannot be used to support use of attapulgite alone. The April 9 meeting was held, in part, to respond to a petition filed by Public Citizen in January seeking a ban of all OTC antidiarrheal products containing kaolin and pectin, activated charcoal and attapulgite. The petition also asked the committee to support oral rehydration therapy as an alternative to these products in the treatment of diarrhea. The joint advisory committee recommendations reverse the antidiarrheal TFM published in April 1986. Under the TFM, attapulgite was moved to Category I from Category III; kaolin and pectin were in Category III. The joint committee recommended that labeling of kaolin-containing OTC products include a statement that children under 12 should not take the product unless a physician has been consulted. Also, because it did not find either kaolin or attapulgite safe or effective for children, the committee agreed that FDA should not require information on oral rehydration therapy in OTC antidiarrheal labeling.