Last October, the Food and Drug Administration took the unprecedented step of switching a prescription medicine to over-the-counter status on its own initiative, without prompting from the medicine's manufacturers.
Now that the product, a popular inhaler sold as Alupent or Metaprel, is on the market, the agency has come under strong criticism and is giving the decision another look.
Dr. James P. Mann, director of the FDA's Division of Surgical-Dental Drug Products and the official primarily responsible for the decision, said he wanted to help many of the millions of asthmatics in this country.
He said the inhalers, which release a "metered dose" of medicine to unclog an asthma victim's air passages, had an unexcelled safety record in a decade of heavy prescription use. Mann said they are not only less prone to overuse than over-the-counter (OTC) aerosols containing epinephrine, but are also more effective.
Mann, who has worked for the FDA for 4 1/2 years, said he thought the switch was so noncontroversial that there was no need to run it by the agency's Pulmonary-Allergy Drugs Advisory Committee. Nor did the agency announce the move with a press release. Instead it published a notice in the Oct. 26 Federal Register, which physicians rarely see.
Even the two manufacturers were caught off guard. Lucrative as the big new OTC market may be, they had not asked the agency to create it and were not ready to move into it.
"We were surprised because we always believed we had to carry the ball," said Dr. Harvey S. Sadow, president of Boehringer-Ingelheim Ltd., the maker of Alupent. The Dorsey Laboratories Division of Sandoz Inc. makes Metaprel.
The move drew heavy fire from some members of the FDA advisory panel and other medical scientists. They contend that some asthma sufferers, particularly adolescents and younger children, will overuse the inhalers and be seriously or even fatally harmed.
Eight of the nine committee members were surveyed, and all said Mann should have consulted them. Several pointed out that England and Australia have already gone in the opposite direction, shifting the inhalers from OTC to prescription status. Two members said they will ask the FDA to withdraw or suspend the decision.
"If I had it do over again," Mann said, "I would have taken it to the advisory committee."
Panel Chairman Anne L. Davis, an associate professor of medicine at Bellevue Hospital in New York, said that the OTC decision had "quite wide implications" and that she has "some reservations" about it.
Panel member William E. Pierson of Seattle, associate director of a children's lung center, said he will urge the FDA to suspend the action pending "a worldwide review." He said he is "very concerned" about possible overuse by adolescents and children, resulting in irregular heartbeat or heart failure. Pierson said he also thought there was not enough data on safe dosages in children.
But panel member A.J. Grant of the University of Texas in Galveston said there are "very compelling arguments on both sides." He and panelist Albert L. Sheffer II of Harvard praised Mann for his scientific abilities.
Other medical experts also expressed concern. Dr. Raymond G. Slavin of St. Louis, president of the American Academy of Allergy and Immunology, said, "The medical and scientific community was not adequately consulted before the decision was made." He pointed out that children under 12, who were not advised to get Alupent and Metaprel inhalers by prescription, may now have easier access to them.
In response to a questionnaire completed by more than 200 members of the allergy academy, 51.4 percent said they "strongly agreed" that making inhalers available over the counter would "result in overuse and abuse . . . by asthmatics." Another 30.4 percent said they agreed with the statement.
While the companies prepared to make their product available to consumers, Dr. Leslie Hendeles, a professor of pharmacology and pediatrics at the University of Florida and the survey's organizer, worked to mobilize his professional colleagues against over-the-counter sales of the inhalers. Hendeles wrote FDA Commissioner Arthur Hull Hayes Jr. in March, asking him to reverse the decision.
Hendeles emphasized data from Australia. The data indicated that inhalers containing the drug in question, metaproterenol sulfate, had a "strong correlation" with asthma deaths. In addition, two Australian scientists who investigated the deaths of 21 asthmatics found a record of excessive use of metaproterenol in 16 cases.
The FDA recently decided to give the panel a chance to discuss the issue at a hurriedly scheduled meeting May 13.
What action may result is uncertain, partly because over-the-counter sales began a couple of months ago, are building rapidly and could be difficult to halt. Television viewers already have begun seeing commercials for "prescription-strength Alupent."