FYI

Eli Lilly's best selling drug, olanzapine (Zyprexa), originally approved
for schizophrenia, then for bi-polar disorder, is prescribed widely.
But the drug has been shown to produce early onset diabetes,
severe hyperglycemia--and deaths. Adolescents and young adults
appear to be at particular risk.

On  November 28, 2001, the Journal of the American Medical Association
published a letter written by Dr. Elizabeth Koller, an FDA medical officer,
Dr. P. Murali Doraiswamy, a Duke University psychiatrist warning that
according to FDA's MedWatch data, patients taking either olanzapine or
clozapine were 10 times more likely to become
diabetic than the general population.
http://jama.ama-assn.org/issues/current/ffull/jlt1128-4.html
 Vol. 286 No. 20,

Those findings have been corroborated by several other studies.
Yet, the FDA has done little to warn doctors and consumers.
Patients taking the drug should, at the very least have their
blood sugar monitored, but if doctors are unaware of the risk
patients are not monitored.

The Baltimore Sun reports:
"Japan's Health Ministry, concerned by reports of two deaths and seven
comas, barred doctors last year from prescribing Zyprexa for any new
patients with diabetes, and warned them to monitor closely those already on
the drug by regularly measuring blood-sugar levels. British drug regulators
issued a warning in April."

According to Dr. Doaiswamy, in Japan, a strong, highlighted warning appears
at the very beginning of the Zyprexa label. The FDA has not required a
warning beyond inconspicuous mention of the possibility of sugar problems in
patients who take atypicals.

Public Citizen advises physicians and consumers to look to the Japanese
label for the most accurate information. It states:

* Olanzapine is contraindicated for use in patients with diabetes or a
history of diabetes.

* Olanzapine should be used with caution in patients with risk factors for
diabetes, including hyperglycemia, obesity or a family history of diabetes.

* Patients receiving olanzapine should be carefully monitored for symptoms
of hyperglycemia and the drug should be discontinued if such symptoms occur.
The symptoms of severe hyperglycemia include weakness, excessive eating,
excessive thirst, and excessive urination.

* Physicians should educate patients and their family members about the risk
of serious hyperglycemia associated with the olanzapine and how to identify
the symptoms of hyperglycemia

See: http://www.citizen.org/eletter/articles/hyperglycemia2.htm

~~~~~~~~~~~~~~~~~~~~~
THE BALTIMORE SUN
http://www.sunspot.net/bal-te.drug19mar19.story

Risks from mental illness drug not adequately noted, some say

Studies link Zyprexa to diabetes deaths

By Timothy B. Wheeler
Sun Staff

March 19, 2003

Rob Liversidge had reason to hope he was on the long road back from the
severe mental illness that had derailed his life.

Aided by a powerful anti-psychotic medication, the 39-year-old Silver Spring
man planned to resume the government career that his bipolar disorder had
interrupted.

But in October, a week before he was to start a new job, Liversidge
collapsed and was rushed to a local hospital. Despite doctors' efforts, he
went into a coma and died four days later.

"It was like he never had a chance," says his mother, Ellen Liversidge. Her
grief about her son's mysterious death turned to anger, however, when she
learned that at least 23 other people had died, and hundreds more suffered
potentially life-threatening illness, while taking the same medication.

Zyprexa, widely prescribed to treat bipolar disorder and schizophrenia, has
been linked in multiple studies in this country and abroad with diabetes and
severe hyperglycemia, a related failure of the body's ability to process
sugar. It can quickly lead to coma and death if not discovered and treated
soon enough.

Those studies, and actions taken recently by drug regulators in other
countries, have prompted some U.S. physicians to call for more prominent
warnings to doctors and the public about the potentially life-threatening
side effects of this otherwise helpful medication.

"It's clear this is not rare," says Dr. E. Fuller Torrey, director of the
Stanley Medical Research Institute in Bethesda, which studies the causes and
cures of schizophrenia. "How common it is is not clear yet, but it's very
serious."

Torrey contends that the Food and Drug Administration, which regulates the
safety of medications, should require a "black-box" warning - with the text
in bold type - on Zyprexa's label about the risks of hyperglycemia and
diabetes. "There's almost no one who's aware of it out there," he said. "You
may be getting deaths of individuals, but no one is putting it together."

An FDA spokeswoman said the agency is reviewing the reports of illness and
death, but declined to provide details.

"FDA is evaluating all this information, and we'll make a determination if
action is needed," said Susan Cruzan, the spokeswoman. She said regulators
are looking at the potential side effects of all anti-psychotic drugs, not
just Zyprexa.

The consumer group Public Citizen is considering whether to ask the FDA to
require a more prominent label warning for Zyprexa and one or more other
anti-psychotic medications that seem to have similar side effects.

"This is a very good drug," said Dr. Sidney Wolfe, executive director of
Public Citizen's Health Watch group. But he added: "You could warn people
better than what looks like the case right now, and allow the use to be
safer."

A spokeswoman for Eli Lilly & Co., which makes Zyprexa, maintains the drug
is safe and effective. "No one has yet proved any sort of causality," said
Marni Lemons, the spokeswoman.

Zyprexa has been the Indianapolis-based drug maker's top-selling
medication - surpassing even the popular antidepressant Prozac - since it
went on the market in 1996. With more than 11 million people taking Zyprexa
worldwide, global sales approached $4 billion last year, Lemons said.

Psychiatrists and other researchers agree that Zyprexa has helped in
treating schizophrenia - a disease characterized by incoherent thinking,
disordered memory and delusions - and in managing bipolar disorder, in which
sufferers swing between moods of elation and depression.

It is part of a "second generation" of anti-psychotic drugs that have come
on the market in the past decade or so, which treat mental illness without
the jerky movements, facial disfiguration and other side effects of
traditional anti-psychotic medications.

Yet there have been reports since the late 1990s noting that patients taking
Zyprexa - as well as some of the other new anti-psychotics - seem prone to
diabetes and related illnesses.

In July, researchers from Duke University and the FDA identified 289 reports
of patients taking Zyprexa who had developed diabetes or hyperglycemia. They
tallied 23 deaths from the mid-1990s through February of last year in the
journal Pharmacotherapy.

Though the researchers concluded that the deaths and the drug were linked,
Dr. Robert W. Baker, Lilly's senior clinical research physician, says the
evidence is not persuasive. "It's especially hard to know what would have
happened to those people on some other treatment or no treatment at all," he
said.

Baker noted that Zyprexa's label does mention that both diabetes and
hyperglycemia were reported during clinical trials of the drug. They are
listed among dozens of "infrequent" adverse effects reported while using the
medication.

FDA's Cruzan said the agency did not see any "affirmative evidence" that
Zyprexa causes or worsens diabetes before approving the drug in the
mid-1990s. "That is still the outstanding question," she added.

Complicating the issue is research showing that more schizophrenics are
diabetic or prone to diabetes than the general population, even without
taking anti-psychotic medications.

"There appears to be some kind of link, we don't really understand its
nature," said Dr. Lisa Dixon, a psychiatrist at the University of Maryland
medical school and with the Veterans Affairs Hospital.

But Dixon and Dr. William Carpenter, director of the Maryland Psychiatric
Research Center at UM, said there are enough reports linking diabetes with
anti-psychotic drugs - particularly Zyprexa and an older drug, Clozaril - to
be careful about prescribing it for patients who are already overweight. One
of Zyprexa's best-known side effects is weight gain, and obesity can lead to
diabetes.

Many who have developed diabetes while taking Zyprexa, like Amanda Yates of
Glen Burnie, had no history of it. The 27-year-old insurance adjuster made
two trips to the emergency room for dangerously high blood-sugar levels and
had to take daily injections of insulin for several months to get her
condition under control. Once her doctor took her off Zyprexa, she
recovered.

"I'm just very, very lucky," she said.

Japan's Health Ministry, concerned by reports of two deaths and seven comas,
barred doctors last year from prescribing Zyprexa for any new patients with
diabetes, and warned them to monitor closely those already on the drug by
regularly measuring blood-sugar levels. British drug regulators issued a
warning in April.

Lilly has been making efforts to alert physicians to diabetes risks in
mentally ill patients through company-sponsored seminars, but the firm
disagrees with Japan's action, Lemons said. Putting warnings on the drug's
label "has the potential to misinform patients and their caregivers, causing
them to cease taking the medication."

Rob Liversidge had conquered his mood swings and suicidal thoughts after two
years of treatment with Zyprexa, his mother said. Of average weight before
he started taking the pills, he gained up to 100 pounds on the drug. "He
didn't feel he had that many choices. He had been on the old
anti-psychotics, and he said they made him feel like a robot," his mother
said.

No one had warned him, though, to have his blood-sugar level checked for
signs of hyperglycemia, which ultimately killed him, she says.

Ellen Liversidge has hired a California law firm and is considering filing a
lawsuit against Lilly. Yet she says her chief aim is to alert others to the
potential hazards of the drug.

"I think it helped Rob," she says. "I'm not damning the drug. I'm damning
the fact there was no warning on the label."

Copyright (c) 2003, The Baltimore Sun

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