Lilly Announces FDA Approval of First Medication for Bipolar
Depression
Symbyax Combines Active Ingredients of Zyprexa and
Prozac to Fill Unmet Medical Need
 |
Symbyax
6 mg/25
mg dosage |
(Dec. 29, 2003) -- Eli Lilly and Company announced today that the U.S. Food
and Drug Administration (FDA) has approved Symbyax™ (olanzapine and fluoxetine HCl) for the
treatment of depressive episodes associated with bipolar disorder.
Symbyax (pronounced SIMM-bee-ax), which is a combination of olanzapine, the
active ingredient in Zyprexa ®, and fluoxetine, the active ingredient in
Prozac ®, is the first FDA-approved medication for bipolar depression, a
notoriously difficult-to-treat condition that afflicts millions of Americans.
"There is a desperate need for an effective treatment for bipolar
depression, a devastating condition which often leads patients to take
their own lives," said Terence A. Ketter, M.D., associate professor of
psychiatry & behavioral sciences, and chief, Bipolar Disorders Clinic,
Stanford University School of Medicine.
"We are pleased to be able to provide clinicians with Symbyax, the
first FDA-approved option to help physicians help their patients with bipolar
depression," said Mauricio Tohen, M.D., Ph.D., Lilly clinical research
fellow, Lilly Research Laboratories and Zyprexa product team leader.
"Patients suffering from this debilitating condition can now benefit from
the combination of the active ingredients in Zyprexa and Prozac, two of the
most successful and proven medications in neuroscience history."
Bipolar disorder is a complex mental illness characterized by debilitating
mood swings ranging from episodes of deep depression marked by feelings of
extreme guilt, sadness, anxiety and, at times, suicidal thoughts to episodes of
mania (abnormal euphoria, elation and irritability), interspersed with periods
of normal mood.
Patients with bipolar disorder spend more than three times longer in the
depressive phase than in the manic phase of the disorder and take longer to
recover from it. Additionally, the depressive phase of bipolar disorder is
associated with higher rates of morbidity and mortality. It is estimated that
one in four people with bipolar disorder will attempt suicide at least once,
and the relative risk of suicide among patients with bipolar depression has
been shown to be nearly 35 times greater than for patients in the manic phase
of bipolar disorder.
Symbyax Patients Experienced Robust Symptom Relief In Clinical Trials
According to a study (Tohen, et al.) published in the November 2003
issue of Archives of General Psychiatry, Symbyax helped to treat the symptoms of bipolar
depression more effectively and at a significantly faster rate than
placebo. In the pooled eight-week studies, patients in the Symbyax group
experienced significantly greater improvement in depressive symptoms at weeks
one, three, four, six and eight, compared with patients taking placebo. That
robust symptom improvement was sustained throughout the entire eight weeks of
the study. In addition, Symbyax patients had no statistically greater risk of
treatment-emergent mania than patients taking placebo. In patients with bipolar
depression, a manic episode is a potential consequence of treatment with a
conventional antidepressant alone.
"Medications that clinicians have traditionally used to treat bipolar
patients in a depressive phase can often take several weeks to work and have
the additional risk of sending the patient into a manic episode," said
Ketter. "Having a medication that can provide symptom relief quickly,
while avoiding mania, will be so important to physicians in effectively
treating patients with bipolar depression, particularly because these
individuals are at a high risk of suicide."
Important Information on Symbyax
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 five 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.
Prescribing Information and Availability
Full prescribing information is accessible at www.symbyax.com. Symbyax will be available
in pharmacies by mid-January of 2004.
Bipolar Disorder Background
Bipolar disorder,
also known as manic-depressive illness, affects an individual's mood,
behavior and thinking. Unlike many illnesses, symptoms may be quite different
in different phases of the illness. Treatment is more challenging because some
therapies that are effective in one phase of the illness may be
counterproductive in another, such as the observation that treatment with an
antidepressant alone can precipitate manic episodes.
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. An estimated 25
percent of patients with bipolar disorder attempt suicide at least once and
approximately 20 percent actually succeed. This is one of the highest rates for
any psychiatric disorder and three times higher than that of the general
population. The World Health Organization estimates that bipolar disorder is
the sixth leading cause of disability in the world.
Zyprexa Background
Zyprexa is indicated in the United States for the treatment of schizophrenia
and the short-term treatment of acute manic episodes associated with bipolar
disorder and for the long-term therapy and maintenance of treatment response of
schizophrenia. Additionally, Zyprexa is under review by the FDA for long-term
maintenance of bipolar disorder. (Zyprexa is not indicated for the treatment of
bipolar depression.) 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,
akathisia, postural hypotension, dry mouth, asthenia, dyspepsia, increased
appetite and tremor.
A small number of patients in premarketing trials experienced asymptomatic
elevations of hepatic transaminase; none of these patients developed jaundice.
Periodic assessment of transaminases is recommended in patients with
significant hepatic disease. Prescribing should be consistent with the need to
minimize the risk of neuroleptic malignant syndrome, tardive dyskinesia,
seizures, and orthostatic hypotension.
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.
Full Zyprexa prescribing information.
Prozac Background
Prozac was the first of a new class of drugs, called selective serotonin
reuptake inhibitors (SSRIs), to be approved for use in the United States. This
type of medication helps patients with depression by increasing the
availability of serotonin in the brain. Scientists believe serotonin affects
many types of activity in the brain, including the regulation of mood.
Prozac was initially approved for treatment of depression in Belgium in 1986
and in the United States in 1987. (Prozac is not indicated for the treatment of
bipolar depression.) Since then, it has been approved and marketed in more than
90 countries and used by more than 40 million people worldwide. The safety and
effectiveness of Prozac have been thoroughly studied in clinical trials with
more than 11,000 patients. There have been more than 3,500 publications on
Prozac in medical and scientific journals.
The most commonly observed adverse events associated with the use of Prozac
vs. placebo in U.S.-controlled clinical trials for depression, obsessive
compulsive disorder (OCD) and bulimia combined were nausea (23 vs. 10 percent),
headache (21 vs. 20 percent), insomnia (20 vs. 11 percent), anxiety (13 vs. 8
percent), nervousness (13 vs. 9 percent) and somnolence (13 vs. 6 percent).
Prozac is contraindicated 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
Prozac. Thioridazine should not be administered with Prozac or within a minimum
of 5 weeks after discontinuing Prozac. Prozac should be discontinued
immediately if rash or other possibly allergic phenomena appear for which an
alternative explanation cannot be identified.
Full Prozac prescribing information.
SOURCE: Eli Lilly press release
More Symbyax Information
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