FDA FINAL MONOGRAPH FOR OTC ANTITUSSIVES EXCLUDES DUPONT's PRESCRIPTION DRUG TESSALON (BENZONATATE); CHLOPHEDIANOL SWITCHED TO OVER-THE-COUNTER STATUS

DuPont's Tessalon (benzonatate) will remain a prescription antitussive, according to FDA's decision in the final monograph for OTC antitussive drug products published in the Aug. 12 Federal Register. Despite the recommendation that benzonatate be given Category I OTC status in the 1983 tentative final monograph, both FDA and DuPont agreed that benzonatate should not be switched from Rx to OTC because of potential concerns about misuse. In 1983, FDA had initiated an OTC switch for the drug, calling it safe and effective for non-prescription use ("The Pink Sheet" Oct. 24, 1983, p. 3). DuPont's Tessalon is currently the only benzonatate product on the market. The company had submitted a supplemental NDA requesting OTC status for the drug in 1981; however, DuPont has since withdrawn its supplemental NDA for OTC status. FDA noted that DuPont, in comments on the tentative final monograph, "requested that benzonatate remain available by prescription only." DuPont predicted that "expanded use of benzonatate by the 'unsophisticated consumer,' not under professional supervision, could further complicate the issue." The DuPont cough product was not reviewed by the OTC Cough/Cold Panel. Therefore, at the time of the TFM, the agency decided to evaluate public comments on the proposed switch in status before allowing OTC marketing. In response to the TFM, FDA received two comments opposing the Rx-to-OTC switch and one in favor of the reclassification. "The agency has reviewed the comments and finds a lack of support in switching benzonatate to OTC status," FDA states in the final monograph. The comments opposing the switch specifically "requested that benzonatate remain a prescription drug because of the possibility of oropharyngeal anesthesia if benzonatate is released in the oral cavity." FDA notes that the anesthetic action could result in choking. Concerns were also raised over the possibility of anaphylactic reactions. However, the antitussive final rule switched one previously Rx-only ingredient to OTC status. The final monograph gives OTC marketing status to chlophedianol hydrochloride based on "a careful review of the approved NDA, the marketing history, the available adverse reaction reports, and safety and effectiveness data in the scientific literature." Because chlophedianol had not been considered by the OTC Cough/Cold Panel, the ingredient's reclassification also depended on comments to the TFM. In 1976, Riker petitioned the agency to allow OTC marketing of its Ulo Syrup, which contained chlophedianol hydrochloride as its active ingredient. The manufacturer has since discontinued the product. The other igredients approved in FDA's final rule for antitussive products are: codeine ingredients (codeine, codeine phosphate, and codeine sulfate), dextromethorphan, dextromethorphan hydrobromide, camphor, and menthol. The "nonmonograph" ingredients include benzonatate, camphor lozenges, cod liver oil. eucalyptol/eucalyptus oil, carbetapentane citrate, and noscapine hydrochloride. In response to a comment requesting that camphor and menthol be placed in Category I for use in a hot steam vaporizer, the agency concurred and included the products in the final rule "as antitussives for individual use in a hot steam vaporizer at concentrations of 0.05 percent menthol or 0.1 percent camphor in the water of the vaporizer." When labeling OTC antitussive products, the final rule states that manufacturers must follow the precise language of the final monograph for warnings, directions and statements of identity. "All required OTC drug labeling other than indications for use . . . must appear in the specific wording established under an OTC drug monograph," FDA says. However, in keeping with FDA's new policy regarding OTC labeling, the agency said it agrees "that flexibility in the expression of antitussive indications is desirable." The final rule also adds two new indications for the APPROVED USES section of the labeling in response to a comment seeking "alternative indications." One indication allows for the labeling to state that an antitussive product temporarily relieves "cough due to minor throat and bronchial irritations" or "cough due to minor bronchial irritation." In addition, an antitussive may relieve "cough as may occur with," "associated with," or "occurring with" a common cold. Another change regarding labeling is the deletion of the word "high" from the warning for antitussives proposed in the tentative final monograph. "Fever may be low grade, moderate, high, intermittent, or sustained," FDA explains. "[T]he agency believes that it is important for the consumer to recognize the presence of fever regardless of whether the fever is high or low." Furthermore, the final monograph states that a warning concerning a persistent cough as a sign of a serious condition be required on all antitussive drug products. Previously, the warning was required only for adults or only for children under 12 years of age.