FDA Approves Injectable Form of Lilly's Zyprexa(R)
30 March 2004 - 11:00PM
PR Newswire (US)
FDA Approves Injectable Form of Lilly's Zyprexa(R) Helps Control
Acute Agitation in Schizophrenia and Bipolar Mania INDIANAPOLIS,
March 30 /PRNewswire-FirstCall/ -- Physicians have a new
fast-acting option for controlling the potentially crippling
effects of acute agitation in patients suffering with schizophrenia
and bipolar mania. The U.S. Food and Drug Administration (FDA) has
approved Zyprexa(R) IntraMuscular (olanzapine for injection), an
injectable form of Lilly's top-selling medication. Clinical data
demonstrate that Zyprexa IntraMuscular enables physicians to
rapidly and dependably relieve patients of the effects of acute
agitation without many of the debilitating side effects of
conventional injectable therapies. This new formulationof Zyprexa
is the first medication in its class to be indicated for the
treatment of acute agitation associated with both bipolar mania and
schizophrenia. Sixty-five percent of hospital-based psychiatrists
or emergency room physicians are not satisfied with current
intramuscular antipsychotic therapies, primarily due to side
effects that are difficult for patients to tolerate and because
patients must be switched to a different oral therapy once they are
stabilized, according to the Psychiatrist International Project
conducted by PKS Research Partners in February 2004. In addition,
60 percent of these physicians said that currently available
intramuscular treatments are not adequate in rapidly calming the
agitated patient, which can help the physician to gain a patient's
trust and cooperation. "Acute agitation is terribly frightening and
potentially dangerous for patients and their caregivers," said
Barry Jones, M.D., professor of psychiatry, McMaster University,
Toronto, Canada. "Zyprexa IntraMuscular enables doctors to help
patients regain control quickly, often with just a single
injection. Further, because Zyprexa IntraMuscular is not overly
sedating, it can help the physician and patient to begin
communicating and working together to achieve treatment goals and
help move the patient's life forward." Acute Agitation Acute
agitation is a well-recognized behavioral syndrome with a range of
symptoms, including hostility, extreme excitement, poor impulse
control, tension and uncooperativeness. The syndrome can occur with
a number of conditions, including schizophrenia and bipolar
disorder. Patients suffering from agitation in its severe forms are
usually in an emergency situation and require immediate treatment
to alleviate personal distress and to prevent harm to themselves
and others. Seamless Transition to Long-term Therapy FDA labeling
for Zyprexa IntraMuscular specifically states that if ongoing
Zyprexa therapy is needed, physicians may transition patients with
schizophrenia and bipolar mania from Zyprexa IntraMuscular to oral
Zyprexa as soon as clinically appropriate. More than 56 percent of
physicians say it is very important or important that an
antipsychotic can be used in an injectable formulation for
agitation andan oral formulation for long-term disease management.
"With Zyprexa IntraMuscular physicians have a new option for
treating agitation in schizophrenia and acute bipolar mania
patients," said Mauricio Tohen, M.D., Dr.P.H., Lilly Distinguished
Scholar. "We can offer highly agitated patients Zyprexa's
dependable control from day one and then smoothly and assuredly
transition them to oral Zyprexa for maintenance treatment." Design
and Results of Pivotal Trials Zyprexa IntraMuscular's efficacy in
controlling acute agitation was evaluated in three randomized,
double-blind, placebo-controlled studies in patients with
schizophrenia (two studies) and bipolar mania (one study). In these
studies, the control of agitation with Zyprexa IntraMuscular was
assessed using several scales, including the Positive and Negative
Symptom Scale Excited Component (PANSS EC). Using these scales,
Zyprexa IntraMuscular was statistically superior to placebo in all
studies. On the primary efficacy measure, the PANSS EC,10 mg
injections of Zyprexa IntraMuscular were significantly superior to
placebo at the first time point measured (15 or 30 minutes) after
injection. In the two studies in agitated patients with
schizophrenia, Zyprexa IntraMuscular was compared to haloperidol
(Haldol(R)) intramuscular and to placebo. The injectable formation
of haloperidol, a first generation or "typical" antipsychotic, has
been the standard of care for acutely agitated patients for many
years. Results showed that both Zyprexa IntraMuscular and
haloperidol intramuscular were superior to placebo. No adverse
event occurred significantly more often with Zyprexa IntraMuscular
than with haloperidol intramuscular. In fact, in these studies,
painful muscle contractions called dystonia occurred in 6.6 percent
of haloperidol intramuscular-treated patients, but did not occur
with Zyprexa IntraMuscular. Additional side effects that occurred
significantly more often with haloperidol intramuscular -- but not
with Zyprexa IntraMuscular -- included tremors, muscle spasms,
indigestion and blurred vision. Zyprexa IntraMuscular was compared
to lorazepam (Ativan(R)) intramuscular and to placebo in the study
involving agitated patients with bipolar mania. Lorazepam, which is
an antianxiety,sedative and anticonvulsant medication, also has
been used for decades. In this study, Zyprexa IntraMuscular was
superior to placebo. No adverse event occurred significantly more
often with Zyprexa IntraMuscular than with lorazepam intramuscular.
Incontrast, nausea and vomiting were reported significantly more
often in lorazepam intramuscular-treated patients than in Zyprexa
IntraMuscular-treated patients. Zyprexa Background and Safety
Information In the three Zyprexa IntraMuscular trials, adverse
events included drowsiness, dizziness and muscle weakness. In
addition, Zyprexa IntraMuscular was associated with infrequent
decreases in blood pressure and heart rate that were clinically
manageable. However, in an open-label clinical pharmacology study
in non-agitated patients with schizophrenia in which the safety and
tolerability of intramuscular olanzapine were evaluated under a
maximal dosing regimen (three 10 mg doses administered 4 hours
apart), approximately one- third of these patients experienced a
significant orthostatic decrease in systolic blood pressure (i.e.,
decrease greater than or equal to 30 mmHg). The risk for
hypotension (low blood pressure), bradycardia (slowing of heart
rate), and sinus pause may be greater in non-psychiatric patients
compared to psychiatric patients who are possibly more adapted to
certain effects of psychotropic drugs. Oral Zyprexa is indicated in
the United States for the short-term and long-term treatment of
schizophrenia, for maintenance in the treatment of bipolar
disorder, 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 14 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 atypicalsshould 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 notbeen 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. In addition,
Lilly has completed a medical review of five placebo-controlled
trials in elderly patients with dementia, and found an increased
incidence of mortality from any cause in the Zyprexa group compared
to patients who took placebo (3.5% vs. 1.5%). In this review, risk
factors that predisposed Zyprexa patients to increased mortality
included age greater than 80 years, sedation, simultaneous use of
certain sedative and anti-anxiety medications (called
benzodiazepines) or presence of pulmonary conditions such as
pneumonia. Lilly is currently addressing this mortality data with
the FDA. Full prescribing information is available at
http://www.zyprexa.com/ . About Eli Lilly and Company 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
IntraMuscular 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. (Logo:
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO)
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO DATASOURCE:
Eli Lilly and Company CONTACT: Marni Lemons of Eli Lilly and
Company, +1-317-433-8990
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