Halcion

XANAX AND HALCION: TWO DRUGS THAT RAISE CONCERN

The bestselling anti-anxiety drug Xanax (generic name: alprazolam) has just been approved for the treatment of panic disorder. Approval came with the provison that its manufacturer, Upjohn, develop labeling that warns of potential adverse reactions. Supplying the patient package insert (PPI) is mandatory, but, unfortunately, its distribution by the prescribing doctor will be voluntary.

The PPI will feature warnings about the rebound effect after discontinuing the drug, the severe difficulty some people have in withdrawal, the alternate treatments that are available, and the risk of withdrawal seizures related to dose. People taking this drug for anxiety should be aware that many of these risks apply to them. Xanax stays in the body a shorter time than most other anti-anxiety drugs and many users suffer withdrawal symptoms long after discontinuation. A rebound effect means an exacerbation of the problem for which the drug has been prescribed, in this case, anxiety or panic, upon withdrawal from the drug.

Request Denied

The FDA denied Upjohn's request for the drug's doctor/pharmacist labeling to recommend a dose of up to 10 mg. per day and a maximum duration of treatment of eight months for panic disorder. (Present labeling for treatment of anxiety advises a maximum dosage of 4 mg. per day and notes that efficacy has not be proven for over four months of use.) The FDA turned down the request because post-marketing reports received by the agency indicated that the incidence of withdrawal seizures was considerably higher for people taking more than 4 mg. per day. The evidence supporting Xanax's efficacy for panic disorder is short-term, and the proposed label change request erroneously implied long-term studies had been conducted.

ONE SMALL STEP TOWARD RECOGNIZING HALCION'S HAZARDS

While the FDA required a new warning about Halcion (generic name: triazolam), the nation's number I sleeping pill, a European psychiatrist has called for an outright ban. The physician/pharmacist drug labeling must now warn of the risk of short-term amnesia. Halcion is a relatively new member of the benzodiazepine "family" of anti-anxiety drugs whose best-known is Valium. Amnesia has been associated only with the benzodiazepines with a short half-life, that is, they are eliminated from the body more quickly. Labeling changes have been recommended by an FDA advisory committee for two other benzodiazepines, temazepam (brand name: Restoril) and flurazepam (brand name: Dalmane), with a short half-life. The amnesia warning-directed at physicians-is not likely to satisfy Ian Oswald, M.D., Department of Psychiatry, Royal Edinburgh Hospital, who has called for Halcion to be banned in a letter to the Editor of The Lancet (19 August 1989). Dr. Oswald reminded readers that ten years ago The Lancet published a letter from a Dutch psychiatrist, C. van der Kroef, who reported his experiences with 25 patients. [Halcion] Triazolam can produce the following symptoms: severe malaise; depersonalisation and derealisation; paranoid reactions; acute and chronic anxiety; continuous fear of going insane; depression and deterioration of existing depression; hyperaesthesia [heightened- sensitivityl, especially for sound but also for smell, taste and light; sometimes hypoaesthesia for the same stimuli; nightmares; restlessness; inability to concentrate; verbal and physical aggression; severe suicidal tendencies; hypnagogic hallucinations; impulse actions; amnaesia. . .." The drug was subsequently banned in Dr. van der Kroefs homeland, the Netherlands.

Dr. Oswald raises important questions about the adequacy of Upjohn's testing of Halcion prior to its approval in Europe and the U.S. The sleeping pill is most often prescribed to middle-aged or older people for months or years. Yet only 11 people over the age of 40 were known to have taken at least a 0.25 mg. triazolam dose for more than two weeks when the drug was first marketed. The drug was approved by the FDA for "short-term management of insomnia," noting that the studies verifying efficacy lasted no more than 42 days.

Upjohn used only breakfast-time questionnaires about the previous night's sleep to ascertain side effects, according to Dr. Oswald. This accounts for why "grogginess" was the only side-effect initially reported, leading to its early reputation as a drug of low toxicity.

After pointing out that many of Dr. van der Kroefs observations of a decade earlier were confirmed subsequently by other investigators, Dr. Oswald called for action to prohibit the sale of Halcion because "it was marketed on the basis of deficient research."

COPYRIGHT 1989 Center for Medical Consumers, Inc.
COPYRIGHT 2004 Gale Group