Halcion

Halcion, America's No. 1 bestselling insomnia drug, was recently banned in Great Britain and severely restricted in France.

Although the details of the British decision remain secret, they are known to involve evidence that the manufacturer, Upjohn, withheld adverse reaction data from the FDA and its British counterpart, the Committee on Safety of Medicine.

RXNEWS obtained a tape of a recent BBC television investigative report about Halcion. Previously unpublished, confidential reports show a pattern of troubling adverse reactions in Upjohn's early clinical trials, and the company's alleged attempts to cover them up. The following is a summary of the reports most disturbing findings:

* A study conducted at Jackson Prison in Michigan was designed to test the effects of 1 mg and .5 mg doses of Halcion on healthy individuals. The BBC journalists located and interviewed six of the original 30 participants; three described serious mental reactions to the drug, including paranoia and hallucinations. Upjohn's official summary was examined by independent experts who found these adverse reactions had been obscured. Although paid and offered better living conditions in exchange for their participation, many prisoners dropped out of the study, according to Upjohn's records. Half of those who stayed said they would never touch Halcion again.

An Upjohn spokesperson cited as evidence of Halcion's safety a 1978 study involving 90 healthy subjects followed over six months. Dr. Samuel Fuerst, a Vicksburg, Mississippi doctor in private practice, was paid by Upjohn to do the study. However, using documents obtained under the U.S. Freedom of Information Act, the journalists found that suspicious FDA investigators reexamined Dr. Fuerst's study documents in 1983 and decided he had faked all the results.

Documents show that as early as 1977 the FDA'S medical review officer, Dr. Theresa Wood, had serious questions about Halcion's safety. By 1982 she was convinced that the British had been right in not allowing the .5 mg dose to be sold. In 1983 the FDA approved marketing of Halcion at.5 mg as well as the lower dosages, despite Dr. Wood's concerns and the British disapproval.

By 1987 the FDA'S Dr. Diane Warsawski, who was tracking spontaneous adverse reaction reports involving Halcion, had concluded that its side effects were eight to 30 times more prevalent than with other marketed sleeping pills. The BBC report claims that Dr. Warsawski's boss, Dr. Paul Leber, was a vigorous defendant of Halcion's safety and did not allow the data to be published.

Holland was one of the first countries in which Halcion was marketed. Within several months, a Dutch psychiatrist, Dr. C. van der Kroef, reported in The Lancet that several of the patients for whom he had prescribed Halcion came back complaining of paranoia, aggression and other adverse mental disturbances. Dr. van der Kroef had welcomed Halcion because of what Upjohn claimed was its effectiveness and few, mostly minor, adverse effects. Within a short time, over 1,000 incidences of adverse drug reactions were reported to Dutch drug monitoring authorities by over 600 doctors. These reports of what came to be known as the "Van der Kroef syndrome" included: anxiety, despair, suicidal tendencies, nightmares and aggression. Holland ended up banning Halcion entirely until just recently, when it was reintroduced but only at doses of .25 mg and lower.

In 1989, the FDA held a special advisory committee conference to discuss growing concerns about Halcion. The committee did not consider the experiences in Europe and heard no report of the findings of Drs. Wood and Warsawski. A spokesperson for Upjohn assured the panel that "...there is no information available to Upjohn outside of this meeting that would tend to substantiate the early warning signal about Halcion." Overlooking the mounting evidence that there were serious problems with Halcion, the advisory committee's only action was to recommend strengthening the package insert warning about memory loss.

Under pressure both from the FDA and the European community, Upjohn announced last month that it would, in the future, provide stronger warnings and new packaging for Halcion. The doctor/pharmacist package insert will be changed to emphasize low dose, short term use and patient monitoring.

Many questions about the safety of Halcion remain unanswered. RxNEWS believes there is sufficient cause for the FDA to consider following England's lead and suspending sales of Halcion. The availability of substitute drugs whose safety and efficacy is more certain than Halcion means that people with severe sleep disorders would not be denied treatment.

COPYRIGHT 1991 Center for Medical Consumers, Inc.
COPYRIGHT 2004 Gale Group