PROMETHAZINE WILL BE LIMITED TO Rx-ONLY STATUS "AT THIS TIME," FDA SAYS IN POLICY STATEMENT; WYETH-AYERST RESPONSE CITES NEED FOR OTC ADVISORY COMMITTEE

FDA is prohibiting over-the-counter sales of promethazine until the agency can review all related data and make a final decision on the safety of the agent for OTC use, FDA announced in a policy statement to appear in the Sept. 5 Federal Register. "FDA has concluded that it should accept the advisory committee's advice and is limiting cough-cold combination drug products containing promethazine hydrochloride to prescription-only status at this time," the notice states. At its July 31 meeting, FDA's Pulmonary-Allergy Drugs Advisory Committee recommended that FDA reverse its decision on allowing OTC marketing of promethazine. The committee suggested that, while available data were inconclusive, the agent might be associated with Sudden Infant Death Syndrome (SIDS) and obstructive apnea ("The Pink Sheet" Aug. 7, p. 10). The agency plans to reopen the administrative record for OTC cough/cold combo products to gather additional information on promethazine. The notice soliciting comments and data will be published in the Federal Register. "FDA is aware that there is some controversy in the scientific and medical communities concerning whether a cause-and-effect relationship exists between use of promethazine hydrochloride containing drug products and the occurrence of SIDS and/or sleep apnea," FDA explained. "There are also differences of opinion whether a modified dosage schedule should be used in elderly patients and on the extent of concern about possible neurologic toxicity resulting from the use of promethazine hydrochloride at proposed OTC dosages. The agency intends to reopen the record . . . to allow additional information to be submitted on these and related subjects." The advisory committee review was prompted by Health Research Group's challenge of FDA's decision to allow the ingredient to go OTC. FDA cleared OTC use of the antihistamine via supplemental NDAs for Wyeth-Ayerst's Phenergan and Phenergan DM, on Aug. 11, 1988, and in the OTC cough/cold combo tentative final monograph, published one day later. HRG and the University of Maryland's SIDS Institute petitioned the agency in December to ban OTC sales and restrict prescription use. * FDA noted that it intends to "fully and thoroughly evaluate the data and information submitted to date . . . and other data and information that may be pertinent . . . before making a final decision concerning OTC status for these products and before responding to the various requests in the citizen petition." Wyeth-Ayerst parent, American Home Products, wrote FDA Aug. 10 to express its "dismay" at the advisory committee's recommendations. The firm maintained that the committee's conclusion underscores the need for a separate advisory committee to deal specifically with OTC issues. "If nothing else," American Home Products Chairman John Stafford stated in the letter, "we believe this episode should motivate FDA to establish an advisory committee for OTC issues exclusively, so that future presenters of OTC matters can receive the fairness and objectivity the FDA procedures are intended to and normally provide." Following the advisory panel's conclusion, Wyeth-Ayerst sent a "Dear Doctor" letter informing physicians that the launch of OTC Phenergan was being "postponed" ("The Pink Sheet" Aug. 21, T&G-8). The launch had initially been scheduled for June, but Wyeth-Ayerst agreed to delay the OTC introduction until September to allow the committee the opportunity to consider the switch. Stafford maintained: "We believe that the advisory committee process worked most unsatisfactorily in this instance and we disagree with the recommendations the committee made." He added that "we look forward to full participation in the careful and correct administrative review of the committee's actions, to which I am sure you are committed." * American Home Products told FDA that it had "submitted to advisory committee review because in our discussion with you in mid-June . . . we believed a clear understanding was reached that the committee would assess OTC marketing of our products in the context of their overall safety, particularly with respect to examination of epidemiological evidence of the relationship of these products to SIDS and sleep apnea." Consequently, the company said it was "dismayed" at the "completely undisciplined examination the committee was permitted to conduct." The committee found a "possible" link between promethazine and SIDS "notwithstanding the complete rejection by every participating expert, even FDA's own, of the scant and admittedly unreliable evidence which exists, suggesting this association." The advisory panel's decision may generate concern over prescription use of promethazine, American Home contends. "The committee's approach, and almost unavoidable resultant conclusion, will cast a undeserved stigma on our product, even in its prescription form, that we will find extremely difficult to dispel, though it is completely unjustified on the basis of scientific evidence," Stafford asserted. House Government Operations/Intergovernmental Relations Subcommittee Chairman Weiss (D-N.Y.) has also gotten involved in the promethazine issue. The subcommittee requested data from FDA on its earlier approval of promethazine as an OTC cold remedy. FDA has reportedly responded to Weiss by sending documents to the subcommittee staff.