No Evidence of Reye’s/Nonaspirin Salicylates Link - Procter & Gamble

Procter & Gamble will continue to support Reye's syndrome warnings for bismuth salicylates, provided that such warnings do not imply the ingredient increases risk of the disease.

P&G, which voluntarily has carried a warning on Pepto Bismol since 1992, supports use of the warning based on concerns the product could mask Reye's syndrome by reducing symptoms such as nausea and vomiting.

The company outlined its position in July 16 comments on the April 17, 2003 final rule on Labeling of Oral and Rectal Over-the Counter Drug Products Containing Aspirin and Nonaspirin Salicylates; Reye's Syndrome Warning.

The FDA-required warning language reads: "Reye's syndrome: Children and teenagers who have or are recovering from chicken pox or flu-like symptoms should not use this product. When using this product, if changes in behavior with nausea and vomiting occur, consult a doctor because these symptoms could be an early sign of Reye's syndrome, a rare but serious illness."

The P&G letter encloses company comments first submitted in 1993. The earlier document urges that warnings be limited to nonaspirin drugs that could be used to self-treat symptoms that may be early signs of Reye's syndrome, because such self-treatment could delay consumers from seeking prompt medical attention, in turn increasing risk if Reye's syndrome is present.

The consumer-products giant differentiated this symptom-masking rationale from the Reye's syndrome warning for aspirin, which is based on an association between use of the ingredient and development of the disease.

The warning contained in the final rule "is consistent with our previous comments," the July 16 letter states.

However, FDA said in the final rule that one warning should apply to all salicylates, regardless of whether the intended use is for symptoms that also can be associated with Reye's.

"Because of the serious consequences of Reye's syndrome," FDA determined, "in the interest of safe use of OTC drug products containing nonaspirin salicylates, these products should bear a warning to alert consumers that children and teenagers recovering from chicken pox or flu-like symptoms should not use these products."

P&G emphasizes the lack of relationship between bismuth subsalicylates and Reye's, acknowledging a statement in the April mongraph that "mandating warnings in an OTC monograph does not require a finding that any or all of the OTC drug products covered by the monograph actually caused an adverse event and the FDA does not so find."

The company agrees with the position that "there is no definitive evidence that drugs containing nonaspirin salicylates significantly increase the risk of Reye's syndrome."

P&G echoed that view in two sets of comments, also submitted July 16, on the OTC antidiarrheal drugs monograph and the proposed "traveler's diarrhea" indication in that monograph.

However, FDA's discussion about the Reye's syndrome warning was somewhat more qualified: "Although it does not have definitive evidence that drugs containing nonaspirin salicylates significantly increase the risk of Reye's syndrome, a number of case reports suggest an association," the agency stated.

FDA noted that a number of these reports involved bismuth subsalicylates and "possible diagnosis" of Reye's (¹ (Also see "Attapulgite, Polycarbophil Excluded From OTC Antidiarrheal Final Monograph" - Pink Sheet, 21 Apr, 2003.), p. 3).

P&G's "traveler's diarrhea" letter responds to a proposed rule issued concurrently with the antidiarrheal monograph, which stated that data submitted by the firm in 1986 "tentatively supports" the ingredient's use for that indication. (² (Also see "Bismuth Subsalicylate “Relieves Travelers’ Diarrhea” Claim Proposed by FDA" - Pink Sheet, 21 Apr, 2003.), p. 4).

P&G supports the proposed monograph amendment to allow bismuth subsalicylate products to carry the indication "controls" or "relieves" traveler's diarrhea, defined by FDA as "most commonly caused by an infectious agent."

The company says the amendment will "provide an effective therapy for the treatment of traveler's diarrhea.

"Procter & Gamble encourages the FDA to expeditiously amend the antidiarrheal monograph so this statement can be used on appropriate OTC products or agree to provide a stay of enforcement letter to companies which so request."