FDA proposes to remove ephedrine OTC status citing abuse, misuse concerns.

EPHEDRINE WITHDRAWAL FROM OTC STATUS PROPOSED BY FDA in a July 27 Federal Register notice. FDA said the notice of proposed rulemaking was issued "in response to a request from the U.S. Department of Justice's Drug Enforcement Administration to restrict OTC availability of ephedrine" because of its use in the illicit manufacturing of controlled substances such as methamphetamine and methcathinone, and due to the potential for misuse and abuse of OTC ephedrine drug products.

Specifically, the proposal would amend the OTC bronchodilator final monograph to remove ephedrine, ephedrine hydrochloride, ephedrine sulfate and racephedrine hydrochloride and classify them as unsafe and ineffective for OTC use. The proposal also would ban combination products containing ephedrine. In a separate Federal Register notice, FDA also issued a final rule to remove theophylline-containing cough/cold products from over-the-counter status. Epinephrine, however, remains a safe and effective OTC bronchodilator ingredient so long as it is administered with a hand-held rubber bulb nebulizer, FDA stressed.

The proposal, FDA explained, would effectively remove "all oral systemically acting bronchodilator drugs from the OTC market."

The July 27 rulemaking follows other federal efforts to establish additional controls on the distribution of ephedrine. An Oct. 11, 1994 DEA final rule subjected all single-entity ephedrine drug transactions, regardless of size, to the applicable record-keeping and reporting provisions of the Controlled Substances Act ("The Tan Sheet" Oct. 17, 1994, p. 5). DEA also published a final rule in June that required single-ingredient OTC ephedrine products to be "stocked behind a counter" in retail establishments "where only employees have access" ("The Tan Sheet" July 3, p. 4).

The agency said that DEA sent a letter to FDA expressing concern that manufacturers of street drugs would "turn to combination drug products containing ephedrine and guaifenesin" in place of single-ingredient ephedrine products since the ephedrine can be "readily isolated" from the combination. The "best resolution for this misuse/abuse problem," the agency concluded, "is for ephedrine, singly or in combination products, not to be available OTC."

FDA said it has received comments from county, state and federal government organizations; pharmacists' organizations; and consumers who objected to the continued marketing of OTC ephedrine drug products because "some manufacturers are promoting these products for misuse as stimulant, weight control, and muscle enhancement products."

The agency said that it "is aware of numerous...reports involving young people who have overdosed by using OTC ephedrine products" which were mispromoted by manufacturers for weight loss or added energy. Overdoses also have occurred through use of "such products for recreational purposes in high doses and on a regular basis." An Indiana addictions program director, for instance, informed FDA that his locality was "experiencing a surge of adverse responses or reactions to the use of OTC ephedrine...for its stimulant effect."

These reports, the agency said, "show that OTC ephedrine drug products are marketed in ways that are misleading, that promote misuse and abuse, and that can be dangerous." Ephedrine misuse and abuse "is a widespread problem in the United States," FDA concluded.

The agency noted that regional responses to the problem of ephedrine abuse have been indicative of its seriousness. FDA pointed out that, "according to one source, at least 14 states have placed additional controls and restrictions on ephedrine," including the switching of the ingredient to prescription-only status "in at least five states." FDA said its proposal, when finalized, "will eliminate the need for future action by individual states."

The proposed rule follows a joint meeting of FDA's Nonprescription and Pulmonary-Allergy Drugs Advisory Committees in November 1994 that was held to discuss the continued OTC availability of asthma drugs ("The Tan Sheet" Nov. 21, 1994, p. 7). At the meeting, committee members "expressed concern about the reports of abuse and illicit diversion of ephedrine" and "one committee member mentioned that the removal of ephedrine from the OTC marketplace...would cause no harm and, indeed, would do some amount of good," FDA summarized.

FDA said it has "determined that legitimate drug manufacturers have little or no interest in single-ingredient OTC ephedrine drug products." The agency conceded, though, that "some manufacturers may have an interest in combination drug products containing ephedrine" and that the rule "would have an impact on consumers who legitimately use OTC" ephedrine products.

However, FDA stated that since OTC bronchodilator drug products are required to bear warnings that they should not be used unless the user's asthma has been diagnosed by a doctor, "it is presumed that legitimate users of these products have seen a doctor and are under a doctor's occasional care for the treatment of their asthma." Such users will be able to obtain the drug by prescription if it is appropriate for the treatment of their condition, the agency added.

Comments on the proposed rule are being accepted until Aug. 28. FDA explained that the short comment period reflects the "existing serious health problem" presented by misuse and abuse of OTC ephedrine products.