UNCOMMON PRACTICE

Patients going beyond drug's label to treat their ailments

Dr. Richard Glogau doesn't have the FDA's blessing when he injects
patients' armpits with botulism toxin to treat their problems with excess
sweat.

But the San Francisco dermatologist administers the unorthodox treatment
regularly winning raves from drenched hyperhidrosis sufferers, a byline in
an upcoming issue of the Journal of Dermatologic Surgery and even a few
visits from intrigued network news shows.

"This is a significant advance for patients," he said.

It also highlights one of the more peculiar features of the American
medical system: Fully half of all prescription drugs sold are used for
aliments other than those they were approved to treat.

Glogan and his patients are pioneers in what's known as "off-label" drug
use. That refers to any use other than that listed on the Food & Drug
Administration approved product description. FDA regulations allow any drug
approved for one condition to be freely prescribed for any other condition,
as long as the doctor sees a benefit.

There's no solid proof of safety and efficacy, but patients often are the
last ones to complain.

"I was desperate," said Brandon Burg, 30, a San Francisco
medical-management software consultant bedeviled since childhood by wildly
overactive sweat glands.

Multiple rounds of painful cutting, scraping and liposuction didn't work.
Ready to try anything, Burg found his way to Glogau's clinic at the
University of California at San Francisco and soon was undergoing
injections of a drug called Botox.

It's sold by Irvin based Allergan Inc. with full approval of the FDA. But
the only FDA-sanctioned use, based on extensive, rigorously controlled
clinical trials, is to control certain nervous disorders affecting muscles
of the eyelids and face.

Botulism toxin is deadly at full strength - a much feared agent of
biological warfare that paralyzes victims in seconds. But in its dilute
form, the same toxin can be used safely to tame overactive nerve junctions
in the muscles.

Along with at least two other researchers showing similar results, Glogau
found that Botox also keeps sweat glands under control, inhibiting the
neurotransmitter that causes muscles surrounding the glands to contract.
The only drawback so far seems to be that the effect wears off in a few
months, forcing patients back for repeat treatments. Each round of
injections costs $600 to $1,000.

From the standpoint of practitioners like Glogau, there's no reason to wait
for the government's permission to do what he can to help people.

"That's not how medicine operates," he said.

Glogau notes that only about half of his patients' insurance companies are
willing to pay for what some consider an experimental cosmetic procedure.

The FDA system doesn't allow Allergan to proclaim Botox's efficacy in
fighting sweat - unless the company is willing to finance full-blown
c~mical trials of Botox for sweat control.

Which it isn't.

Instead, Allergan is studying Botox as a treatment for cerebral palsy,
migraine headache, adult spasticity, spi~al cord in-jury and lower back
pain.

"You want to take a look at the bigger markets obviously because they bring
are-turn on your investment faster," said an Allergan spokesman. "Excess
sweating af-fects a narrow range of the population. It's not a place where
we have placed a lot of research money."

In fact, the company can't even say very much about what independent
researchers are doing. Even while drug ads flourish on TV, manufacturers
are strictly forbidden to discuss off-label uses of their products. This
policy is supposed to provide an incentive for the company to undergo
expensive product testing.

Now, though, the restrictions are starting to ease.

Congress ordered the FDA to implement new rules by November that allow
companies to hand out unsolicited copies of materials on off label drug
use. However, only medical-journal articles and other specialty materials
can be distributed, and then only if the drugmaker undertakes a clinical
trial within three years.

"There's an open question as to how much this will change things," said
Michael Landa, staff attorney at Fenwick & West in WashingtQn, D.C.

Some legal specialists charge the new law doesn't go nearly far enough,
suggesting there's no reason to restrict the free flow of information to
physicians trained to digest it.

"There's a natural conservatism among physicians, a built-in skepticism
about any new drug or untried use of an old drug," said Jonathan Emord, a
Washington, D.C., lawyer representing doctors and some health-product
makers.

"Not many doctors are eager to be on the cutting edge experimenting with
human beings as guinea pigs. There are some cases where they have no
choice. To fear the dissemination of science to scientists is just absurd,"
Emord said.

But most drugmakers seem reluctant to press the point, partly because the
1997 law eased other restrictions, such as those on advertising, that they
had chafed against, partly because doctors can find all the information
they need and then some just by searching the Internet.

"I haven't heard many complaints," said Carl Feldbaum, president of the
Biotechnology Industry Organization. He called the new change on off label
information "a careful compromise."

Many patient groups wanted the off-label rules lifted altogether, but
consumer advocates maintain it would be a big mistake to give manufacturers
free rein.

"The system is supposed to provide an incentive to conduct studies, and
this amounts to an end-run around the system," said Arthur Levin, director
of the Center for Medical Consumers, an advocacy group based in New York.