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Executive Summary

OTC PHENERGAN LABELING WILL CONTRAINDICATE USE in children under two years of age, Wyeth-Ayerst stated in recent comments to FDA. "Wyeth-Ayerst agrees that promethazine should not be used in infants, and has determined to label any OTC promethazine-containing drug marketed by it similarly to its prescription promethazine products, so as to clearly state that the drug is not to be used in children under two years of age," the firm said. Wyeth-Ayerst's comments were submitted in response to Public Citizen Health Research Group's (HRG) citizen petition requesting an immediate ban on OTC sales of products containing promethazine HCl, including Wyeth-Ayerst's Phenergan DM and Phenergan VC. The petition, submitted by HRG and the University of Maryland's Sudden Infant Death Institute, was filed with FDA on Dec. 14 ("The Pink Sheet" Dec. 19, 1988, T&G-14). The petition asserts that "use of promethazine syrups at therapeutic doses has been highly significantly associated with Sudden Infant Death Syndrome (SIDS) in one study, and with an increase in infant sleep apneas, in another." The petition also requests that FDA require a mandatory patient package insert that would caution against the products' use by children under the age of two and by pregnant or breast feeding women, and that a modified dosage schedule be used for the elderly. Additionally, HRG asked that FDA change the physician labeling to include a bold, boxed warning with similar cautions. Wyeth-Ayerst received approval for OTC marketing of Phenergan DM and Phenergan VC on Aug. 11, 1988 via supplemental NDAs ("The Pink Sheet" Oct. 24, T&G-1). One day later, FDA published the tentative final monograph for combination cough/cold products, which allowed promethazine-based combinations to be marketed OTC. HRG reiterated its request to prevent OTC sales in an April 17 letter to FDA Commissioner Young. The group noted that "four months have lapsed since lodging our petition [and] there has been no official response." HRG stated that since the petition was filed there has been a report of a "death of a six-week old infant, who died after being given Phenergan prescribed for colic" and a report of "two 'near-miss SIDS' episodes associated with Phenergan." The two cases are discussed in a paper to be published on May 5 in Pediatrics, HRG added. HRG's letter cited a 1982 case-control study of children dying of SIDS in Belgium. The study has shown that the children "are ten times more likely than controls to have been given promethazine [or] an analog." In its comments, Wyeth-Ayerst described the study as "flawed and inconclusive." The company stated that the study is "not well controlled," since "the control subjects were, among other deficiencies, drawn from referrals and thus were not randomly selected." Wyeth-Ayerst added that "the incidence of administration of particular phenothiazines (promethazine or alimemazine) is not stated." Wyeth-Ayerst also noted that FDA Office of Epidemiology and Biostatistics Director Gerald Faich, MD, "found the study to be flawed," noting that the case-control study, as well as other published studies, were submitted to FDA as part of the Phenergan filings. Summarizing its response to HRG's assertions, Wyeth-Ayerst said: "The petition is based on (1) reports or data on adverse events involving largely either phenothiazines other than promethazine, or where a causal association with promethazine has not been established, and (2) reports or data involving promethazine use as a single ingredient and at doses far in excess of those permitted for OTC use . . . as well as in excess of drug prescription limits in some cases."

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