SANDOZ' TAVIST-1 "LOW DROWSINESS" NEWSPAPER AD CLAIM IS BASED ON DATA PREVIOUSLY FOUND INADEQUATE TO ALLOW LABEL CHANGE, AGENCY TELLS FIRM

Sandoz's Tavist-1 daily newspaper ad claim of "low drowsiness" is based on data that FDA concluded in 1985 was inadequate to support a label change, the agency said in an Oct. 19 letter to the firm. In 1985, the letter points out, Sandoz subsidiary Dorsey Labs submitted a supplemental NDA seeking to switch Tavist-1 from prescription to OTC and to include the claim, "Unique, clinically proven low drowsiness (7% incidence) antihistamine." FDA's Surgical/Dental Drug Products Division rejected the claim, telling Sandoz that "information regarding the low incidence of drowsiness and decrease of drowsiness with continued use should be deleted in the absence of data comparing the degree of drowsiness of clemastine to other antihistamines." FDA said it based its rejection of the low-drowsiness claim on the absence of studies showing that the product caused a lower rate of drowsiness than other antihistamines. The company's original Tavist-1 NDA, submitted in 1977, contained two placebo comparison clinical studies. The letter from FDA Office of Drug Standards Director Peter Rheinstein, MD, was in response to Tavist-1 newspaper advertisements appearing in mid-September ("The Pink Sheet" Sept. 21, p. 3). At the request of FDA, Sandoz put the ads on hold beginning Sept. 25. "The agency considers the comparative safety and effectiveness claims made in this advertisement to be false and misleading," the letter states. "The implication that Tavist-1 is less sedating than other antihistamines raises a safety concern. Finally, the advertisement's headline 'Special Update for Doctors' implies that Tavist-1 is new, which is not correct." The product has been marketed in the U.S. since 1979, and newness claims are limited to a six-month period after initial domestic marketing, according to the agency. In a press statement prepared Oct. 23, Sandoz noted that FDA "has raised a question concerning the claim for low drowsiness." The company stated: "We are certain that this claim, made in our ad, is appropriate and, in fact, was approved by the FDA in 1982." Sandoz added that the advertisement "would never have been published without the advice and approval of the FDA." FDA indicated that Sandoz would have to conduct clinical studies comparing Tavist-1 to other antihistamines before a superior efficacy claim could be made. "There is evidence, however, from a controlled direct comparison study not performed by Sandoz, that Tavist-1 is in fact less effective than one of its major competitors," the agency added, not naming the product. Sandoz' claim of a 7% "net rate" of drowsiness, according to FDA, appeared to be based on data from six studies submitted with the NDA supplement in 1985, in which a range of 4-25% drowsiness was seen with Tavist-1. "Patients with a high rate of sedation from one investigator were excluded, placebo rates were subtracted and inappropriate statistical methods were used," the letter states. Also under question is the advertisement's reference to "net rate," a non-standard term that the agency feels requires further clarification. Rep. Dingell's (D-Mich.) Energy & Commerce oversight subcommittee is planning to take a look at FDA's activities regarding the Tavist-1 newspaper ads. In an Oct. 21 letter to the agency, Dingell requested all documents relating to FDA's consideration of the Sandoz ad. An Oct. 14 meeting between Sandoz and FDA was postponed and has not yet been rescheduled. In the meantime, the agency has requested that Sandoz confirm within 10 days after receipt of the letter that the advertisement has been canceled and will not be resumed.