Bismuth Subsalicylate Inclusion In Overindulgence TFM Urged By P&G

An FDA request for more information on a 13-year-old Procter & Gamble submission on bismuth subsalicylate could indicate the agency's interest in moving towards completion of the overindulgence monograph.

FDA maintains the request simply reflected normal procedures, noting if the agency "receive[s] a comment to a particular rulemaking that does not provide enough information, we will follow up with the commenter to probe for additional information that would help us to consider their proposal."

In the same vein, the agency did not include the TFM for overindulgence products in its unified agenda released in June (¹ (Also see "HHS “Unified Agenda” Shows FDA Lagging On OTC Actions" - Pink Sheet, 5 Jul, 2004.), p. 12).

In July, P&G submitted four studies and additional literature in support of an original set of comments filed with the agency in 1991, when the TFM was first released. The firm markets bismuth subsalicylate-containing Pepto-Bismol chewable tablets, caplets and liquid.

The consumer research surveys, which included a U.S. nationally representative sample, were conducted by P&G; some were mail-back, self-completed questionnaires, while others required participants to keep a diary of familial stomach symptoms.

Based on the studies, the Cincinnati-based firm "continues to recommend that 'indigestion' be added to the symptoms associated with upset stomach due to overindulgence [of food] and drink."

Results of a survey involving more than 1,100 participants show "the words used to describe feelings associated with 'indigestion' and 'upset stomach,' with respect to the symptoms for which bismuth subsalicylate has Category I [safe and effective] status, were virtually indistinguishable," the comments state.

A second survey of 310 adults similarly supports those findings, P&G adds.

Moreover, the firm says survey findings of 450 households demonstrate that familial stomach symptoms experienced in a week did not discriminate based on age; the number of family members experiencing discomfort ranged from 5% to 10% in all age groups.

In addition, a mail-back survey of 159 parents indicated "the cause of upset stomach is as likely to be attributed to overindulgence in food and drink for children...as for adults."

The TFM therefore should be amended "to include dosing regimens for bismuth subsalicylate for relief of upset stomach due to overindulgence in food and drink in children aged 3 to 12 years," the submission states.

"We also recommend that the adult dose for bismuth subsalicylate for [overindulgence relief] be consistent with the dose for adults...regulated to the recently finalized Anti-Diarrheal OTC Drug Monograph," which was released in April 2003 (² (Also see "Attapulgite, Polycarbophil Excluded From OTC Antidiarrheal Final Monograph" - Pink Sheet, 21 Apr, 2003.), p. 3).

According to this scheme, children between ages nine and 12 would receive an adult dose for both Regular and Maximum Strength Pepto-Bismol, while children ages six through nine would receive 175 mg and 350 mg, respectively and those ages three to six would get 131 mg and 263 mg, depending on the strength.

Almost one year following finalization of the monograph, bismuth subsalicylate products were granted the "traveler's diarrhea" indication (³ 'The Tan Sheet' May 17, 2004, In Brief).

Finally, P&G seeks inclusion of combination bismuth subsalicylate and simethicone products "for the relief of gas and upset stomach" in the overindulgence monograph.

"When used under adequate directions for use and warnings against unsafe use specified in the monographs for each active ingredient, a bismuth subsalicylate and simethicone combination drug would...provide rational concurrent therapy for a significant proportion of the target population," the firm maintains.

Consumer studies show the safety and effectiveness of the two ingredients are not decreased in combination, an important finding since a separate study of 159 participants "showed that gas frequently occurs concurrently with the symptoms for which bismuth subsalicylate has shown to be effective."