FDA Approves Zyprexa(R) for Maintenance of Bipolar Disorder
First Atypical Antipsychotic Approved for Treatment of
Bipolar Mania Is First Mania Treatment in 30 Years to Receive
Additional Approval for Bipolar Maintenance
INDIANAPOLIS, Jan. 14 /PRNewswire-FirstCall/ -- The U.S. Food and Drug
Administration (FDA) has approved Zyprexa(R) (olanzapine) for maintenance in
the treatment of bipolar disorder, Eli Lilly and Company announced today.
This FDA approval recognizes that Zyprexa is an effective treatment to delay
relapse into either mania or depression in patients with bipolar disorder.
Zyprexa is the first treatment in nearly 30 years to be recognized by the FDA
as a treatment for both acute mania and maintenance treatment in bipolar
disorder.
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"Bipolar disorder is a serious condition that can be difficult to treat.
For those who achieve stability on existing medications, relapse of symptoms
is all too common," said Frederick K. Goodwin, MD, Director, Center on
Neuroscience, Medical Progress and Society, at the George Washington
University Medical Center, Washington, D.C. "It is good news that the FDA has
now approved Zyprexa as a new tool for physicians to use to delay relapse and
prolong periods of stability and wellness."
Zyprexa was approved by the FDA in 2000 for the short-term treatment of
acute mixed or manic episodes associated with bipolar disorder and is the
first medication approved to both treat acute mania and delay relapse of
symptoms associated with bipolar disorder since lithium received approval from
the FDA in 1974. In addition, the FDA recently approved Symbyax(TM) for the
treatment of bipolar depression. Symbyax combines the active ingredients in
Zyprexa and Prozac(R), and is the first and only FDA-approved treatment for
this devastating and difficult-to-treat phase of bipolar disorder.
Zyprexa Delayed Relapse Into Both Mania and Depression in Clinical Trials
The new indication is based on data from a double-blind, placebo-
controlled study that showed time to relapse of either mania or depression was
significantly longer for Zyprexa patients than patients treated with placebo.
Zyprexa-treated patients had a significantly lower rate of either a mania
(16.4 percent for Zyprexa versus 41.2 percent for placebo) or depression
relapse (34.7 percent for Zyprexa versus 47.8 percent for placebo).
"We believe that physicians are looking for treatments, like Zyprexa, that
demonstrate that they can effectively delay relapse, not only into the manic
phase, but also into the depressive phase of bipolar disorder," said Mauricio
Tohen, MD, Dr. P.H., Lilly clinical research fellow, Lilly Research
Laboratories and Zyprexa product team leader. "This new indication provides a
treatment option to clinicians and patients that is dependable in treating
both acute manic episodes and delaying new episodes. Longer stable periods
may provide greater opportunities for clinicians to work with their patients
on improving work or family life."
In the placebo-controlled study, common and significant adverse events for
the Zyprexa patients were weight gain, fatigue and inner and outer
restlessness (akathisia).
About Bipolar Disorder
Bipolar disorder, also known as manic-depressive illness, is a complex
mental illness characterized by debilitating swings in mood. These swings
range from manic episodes, marked by abnormal euphoria, elation and
irritability, to episodes of deep depression, marked by extreme sadness and
difficulty functioning. These periods of illness are interspersed with
periods of normal mood. Although a lifelong illness, bipolar disorder
typically emerges in adolescence or young adulthood, and episodes continue
intermittently throughout life.
More than 2.5 million Americans live with a diagnosis of bipolar disorder
but recent research indicates the real number may be as high as 10 million.
The results of untreated bipolar disorder can be catastrophic. According to
the National Institute of Mental Health, nearly one in every five people with
the illness ends their life by suicide. The World Health Organization
estimates that bipolar disorder is the sixth leading cause of disability in
the world.
During relapse into mania or depression, people with bipolar disorder may
experience disruptions in relationships and jobs, suffer feelings of failure
or become suicidal. Recurring relapse may lead to both a worsening of the
disease itself and may contribute to more frequent episodes of relapse.
Important Information About Zyprexa and Symbyax
In addition to the newly approved indication, Zyprexa is indicated in the
United States for the short-term and long-term treatment of schizophrenia, and
either alone or in combination with lithium or valproate (Depakote(R), Abbott)
for the short-term treatment of acute mixed or manic episodes associated with
bipolar disorder. Since Zyprexa was introduced in 1996, it has been
prescribed to more than 12.5 million people worldwide.
The most common treatment-emergent adverse event associated with Zyprexa
in placebo-controlled, short-term schizophrenia and bipolar mania trials was
drowsiness. Other common events were dizziness, weight gain, personality
disorder (COSTART term for nonaggressive objectionable behavior),
constipation, restlessness, episodes of low blood pressure, dry mouth,
weakness, upset stomach, increased appetite, and tremor. A small number of
patients experienced asymptomatic elevations of certain liver enzymes; none of
these patients experienced jaundice.
Hyperglycemia, in some cases associated with ketoacidosis, coma, or death,
has been reported in patients treated with atypical antipsychotics including
Zyprexa. Assessment of the relationship between atypical antipsychotic use
and glucose abnormalities is complicated by the possibility of an increased
background risk of diabetes mellitus in patients with schizophrenia and the
increasing incidence of diabetes mellitus in the general population. The
available data are insufficient to provide reliable estimates of differences
in hyperglycemia-related adverse event risk among the marketed atypical
antipsychotics. All patients taking atypicals should be monitored for
symptoms of hyperglycemia. Persons with diabetes who are started on atypicals
should be monitored regularly for worsening of glucose control; those with
risk factors for diabetes should undergo baseline and periodic fasting blood
glucose testing. Patients who develop symptoms of hyperglycemia during
treatment should undergo fasting blood glucose testing.
Prescribing should be consistent with the need to minimize the risk of
neuroleptic malignant syndrome, tardive dyskinesia, seizures and low blood
pressure.
In short-term (six-week) acute bipolar mania trials in combination with
lithium or valproate, the most common treatment emergent adverse event
associated with Zyprexa and lithium or valproate was dry mouth. Other common
events were weight gain, increased appetite, dizziness, back pain,
constipation, speech disorder, increased salivation, amnesia and abnormal
burning or tingling of the skin.
Although the efficacy of Zyprexa in elderly patients with dementia has not
been established in clinical trials and Zyprexa is not approved for use in
this patient population, it is important to note the label for Zyprexa
includes a warning for elderly patients with dementia. The warning states
that strokes or mini-strokes (also called transient ischemic attacks or TIAs),
including fatalities were reported in elderly patients with dementia-related
psychosis participating in Zyprexa clinical trials.
Full prescribing information is available at http://www.zyprexa.com .
Symbyax is indicated in the United States for the treatment of depressive
episodes associated with bipolar disorder.
The most common adverse events reported in patients taking Symbyax in
clinical trials was drowsiness. Other common events noticed in clinical
trials were weight gain, increased appetite, feeling weak, swelling, tremor,
sore throat, and difficulty concentrating.
Hyperglycemia, in some cases associated with ketoacidosis, coma or death,
has been reported in patients treated with atypical antipsychotics, including
olanzapine, and concomitant olanzapine and fluoxetine. Assessment of the
relationship between atypical antipsychotic use and glucose abnormalities is
complicated by the possibility of an increased background risk of diabetes
mellitus in patients with schizophrenia and the increasing incidence of
diabetes mellitus in the general population. The available data are
insufficient to provide reliable estimates of differences in hyperglycemia-
related adverse-event risk among the marketed atypical antipsychotics. All
patients taking atypicals should be monitored for symptoms of hyperglycemia.
Persons with diabetes who are started on atypicals should be monitored
regularly for worsening of glucose control; those with risk factors for
diabetes should undergo baseline and periodic fasting blood-glucose testing.
Patients who develop symptoms of hyperglycemia during treatment should undergo
fasting blood-glucose testing.
Although Symbyax is not approved for elderly patients with dementia it is
important to note the label for Symbyax includes a warning for patients in
this population. The warning states that strokes or mini-strokes (also called
transient ischemic attacks or TIAs), including fatalities were reported in
elderly patients with dementia-related psychosis participating in clinical
trials for olanzapine, an active ingredient in Symbyax. In fact, Symbyax has
not been studied in elderly patients with dementia, nor do we expect Symbyax
to be used to treat these patients.
Symbyax may induce orthostatic hypotension (a drop in blood pressure when
standing up), associated with dizziness, speeding or slowing of heart rate,
and in some patients, fainting, especially during initial therapy.
Symbyax prescribing should be consistent with the need to minimize the
risk of neuroleptic malignant syndrome, tardive dyskinesia, and orthostatic
hypotension.
Symbyax should not be administered until at least two weeks have passed
since discontinuing an MAO inhibitor, and an MAO inhibitor is contraindicated
for at least five weeks after discontinuation with Symbyax. Thioridazine
should not be administered with Symbyax or within a minimum of 5 weeks after
discontinuing Symbyax. Symbyax should be discontinued immediately if rash or
other possibly allergic phenomena appear for which an alternative explanation
cannot be identified.
Due to the cyclical nature of bipolar disorder, patients should be
monitored for the signs of mania and hypomania during treatment with Symbyax.
Patients should inform their physicians if they are taking Zyprexa,
Prozac, Sarafem or fluoxetine.
Full prescribing information is available at http://www.symbyax.com .
Lilly, a leading innovation-driven corporation, is developing a growing
portfolio of first-in-class and best-in-class pharmaceutical products by
applying the latest research from its own worldwide laboratories and from
collaborations with eminent scientific organizations. Headquartered in
Indianapolis, Ind., Lilly provides answers -- through medicines and
information -- for some of the world's most urgent medical needs. Additional
information about Lilly is available at http://www.lilly.com .
This press release contains forward-looking statements about the potential
of Zyprexa for maintenance treatment of bipolar disorder and reflects Lilly's
current beliefs. However, as with any pharmaceutical product, there are
substantial risks and uncertainties in the process of development and
commercialization. There is no guarantee that the product will prove to be
commercially successful. For further discussion of these and other risks and
uncertainties, see Lilly's filings with the United States Securities and
Exchange Commission. Lilly undertakes no duty to update forward-looking
statements.
SOURCE Eli Lilly and Company
