WILMINGTON, Del., Jan. 2 /PRNewswire-FirstCall/ -- AstraZeneca (NYSE:
AZN) today announced that the company has submitted two separate
supplemental New Drug Applications (sNDAs) to the U.S. Food and Drug
Administration (FDA) for once-daily SEROQUEL XR(TM) (quetiapine fumarate)
Extended-Release Tablets to seek approval for the treatment of manic
episodes associated with bipolar disorder and the treatment of depressive
episodes associated with bipolar disorder.
The bipolar mania submission is based on a clinical study of once-daily
treatment with SEROQUEL XR, compared to placebo, with a primary endpoint of
change in YMRS (Young Mania Rating Scale) total score (week 3), in 316
patients suffering from bipolar mania. The bipolar depression submission is
supported by a clinical study of once-daily treatment with SEROQUEL XR,
compared to placebo, with a primary endpoint of change from baseline in
MADRS (Montgomery Asberg Depression Rating Scale) total score after 8 weeks
of treatment, in 280 patients diagnosed with bipolar depression(1). Doses
of SEROQUEL XR administered in both the bipolar mania (400 mg to 800
mg/day) and bipolar depression (300 mg/day) studies were comparable to the
FDA-approved recommended doses for SEROQUEL (quetiapine fumarate) immediate
release tablets in those indications(1,2). Both studies met their primary
endpoint and it is expected that they will be presented at major scientific
congresses in 2008.
SEROQUEL XR is currently approved in 8 countries including the U.S.,
Canada and The Netherlands, for the acute and maintenance treatment of
schizophrenia in adults.
Launched in 1997, SEROQUEL has been prescribed to millions of patients
worldwide. It is approved in 88 countries for the treatment of
schizophrenia, in 79 countries for the treatment of bipolar mania, and in
11 countries including the U.S. for the treatment of bipolar depression.
SEROQUEL XR was launched for the treatment of schizophrenia in the U.S. in
2007, and clinical development programs and regulatory filings are planned
for a number of other indications.
Important Safety Information for SEROQUEL and SEROQUEL XR
SEROQUEL XR is indicated for the acute and maintenance treatment of
schizophrenia. SEROQUEL is indicated for the treatment of depressive
episodes in bipolar disorder; acute manic episodes in bipolar I disorder,
as either monotherapy or adjunct therapy to lithium or divalproex; and
schizophrenia. Patients should be periodically reassessed to determine the
need for treatment beyond the acute response.
Elderly patients with dementia-related psychosis treated with atypical
antipsychotic drugs are at an increased risk (1.6 to 1.7 times) of death,
compared to placebo (4.5% vs 2.6%, respectively). SEROQUEL and SEROQUEL XR
are not approved for the treatment of patients with dementia-related
psychosis. (See Boxed Warning.)
Antidepressants increased the risk of suicidal thinking and behavior in
children, adolescents, and young adults in short-term studies of major
depressive disorder and other psychiatric disorders. Patients of all ages
started on therapy should be observed closely for clinical worsening,
suicidality, or unusual changes in behavior. Families and caregivers should
be advised of the need for close observation and communication with the
prescriber. SEROQUEL and SEROQUEL XR are not approved for use in patients
under the age of 18 years. SEROQUEL XR is not approved for the treatment of
depression; however, SEROQUEL is approved for the treatment of bipolar
depression. (See Boxed Warning.)
Hyperglycemia, in some cases extreme and associated with ketoacidosis,
hyperosmolar coma, or death, has been reported in patients treated with
atypical antipsychotics, including quetiapine. The relationship of atypical
use and glucose abnormalities is complicated by the possibility of
increased risk of diabetes in the schizophrenic population and the
increasing incidence of diabetes in the general population. However,
epidemiological studies suggest an increased risk of treatment-emergent,
hyperglycemia-related adverse events in patients treated with atypical
antipsychotics. Patients starting treatment with atypical antipsychotics
who have or are at risk for diabetes should undergo fasting blood glucose
testing at the beginning of and periodically during treatment. Patients who
develop symptoms of hyperglycemia should also undergo fasting blood glucose
testing.
A potentially fatal symptom complex, sometimes referred to as
Neuroleptic Malignant Syndrome (NMS), has been reported in association with
administration of antipsychotic drugs, including quetiapine. Rare cases of
NMS have been reported with quetiapine. Clinical manifestations of NMS are
hyperpyrexia, muscle rigidity, altered mental status, and evidence of
autonomic instability (irregular pulse or blood pressure, tachycardia,
diaphoresis, and cardiac dysrhythmia). Additional signs may include
elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute
renal failure. The management of NMS should include immediate
discontinuation of antipsychotic drugs.
Tardive dyskinesia (TD), a potentially irreversible syndrome of
involuntary dyskinetic movements, may develop in patients treated with
antipsychotic drugs. The risk of developing TD and the likelihood that it
will become irreversible are believed to increase as the duration of
treatment and total cumulative dose of antipsychotic drugs administered to
the patient increase. TD may remit, partially or completely, if
antipsychotic treatment is withdrawn. Quetiapine should be prescribed in a
manner that is most likely to minimize the occurrence of TD.
Leukopenia, neutropenia, and agranulocytosis (including fatal cases),
have been reported temporally related to atypical antipsychotics, including
quetiapine. Patients with a pre-existing low white blood cell (WBC) count
or a history of drug induced leukopenia/neutropenia should have their
complete blood count monitored frequently during the first few months of
therapy. In these patients, SEROQUEL and SEROQUEL XR should be discontinued
at the first sign of a decline in WBC absent other causative factors.
Patients with neutropenia should be carefully monitored, and SEROQUEL and
SEROQUEL XR should be discontinued in any patient if the absolute
neutrophil count is < 1000/mm.
Warnings and Precautions also include the risk of orthostatic
hypotension, cataracts, seizures and hyperlipidemia. Examination of the
lens by methods adequate to detect cataract formation, such as slit lamp
exam or other appropriately sensitive methods, is recommended at initiation
of treatment, or shortly thereafter, and at 6-month intervals during
chronic treatment.
The most commonly observed adverse events associated with the use of
SEROQUEL monotherapy versus placebo in clinical trials for schizophrenia
and bipolar disorder were dry mouth (9%-44% vs 3%-13%), sedation (30% vs
8%), somnolence (18%-28% vs 7%-8%), dizziness (11%-18% vs 5%-7%),
constipation (8%- 10% vs 3%-4%), SGPT increase (5% vs 1%), dyspepsia (5%-7%
vs 1%-4%), lethargy (5% vs 2%), and weight gain (5% vs 1%). The most
commonly observed adverse events associated with the use of SEROQUEL versus
placebo in clinical trials as adjunct therapy with lithium or divalproex in
bipolar mania were somnolence (34% vs 9%), dry mouth (19% vs 3%), asthenia
(10% vs 4%), constipation (10% vs 5%), abdominal pain (7% vs 3%), postural
hypotension (7% vs 2%), pharyngitis (6% vs 3%), and weight gain (6% vs 3%).
The most commonly observed adverse events associated with the use of
SEROQUEL XR versus placebo in clinical trials for schizophrenia were dry
mouth (12% vs 1%), constipation (6% vs 5%), dyspepsia (5% vs 2%), sedation
(13% vs 7%), somnolence (12% vs 4%), dizziness (10% vs 4%), and orthostatic
hypotension (7% vs 5%).
In long-term clinical trials of quetiapine, hyperglycemia (fasting
glucose greater than or equal to 126 mg/dL) was observed in 10.7% of
patients receiving quetiapine (mean exposure 213 days) vs 4.6% in patients
receiving placebo (mean exposure 152 days).
Please see Prescribing Information, including Boxed Warnings, for
SEROQUEL and SEROQUEL XR.
About Bipolar Disorder
Approximately eight million American adults are affected by bipolar
disorder, a serious psychiatric condition also known as manic depressive
illness(3,4). Bipolar disorder consists of recurring episodes of mania and
depression. Bipolar I disorder is characterized by one or more manic or
mixed episodes, often with episodes of major depression, whereas bipolar II
disorder is distinguished by one or more major depressive episodes
accompanied by at least one hypomanic episode(5). In the long term,
patients with bipolar I disorder experience depressive symptoms --
including prolonged periods of sadness, loss of energy, persistent
lethargy, and recurring thoughts of death or suicide(6) - three times
longer than manic symptoms(7). Similarly, patients with bipolar II disorder
spend almost forty times longer in the depressed state than in
hypomania(8). Bipolar disorder is often misdiagnosed as unipolar
depression. This misdiagnosis can lead to unfocused treatment that may
exacerbate the disease. In fact, many patients face up to ten years without
appropriate treatment before a correct diagnosis is made(9). Up to 50
percent of patients with bipolar disorder attempt suicide, and
approximately 15 to 20 percent complete suicide(10).
About AstraZeneca
AstraZeneca is a major international healthcare business engaged in the
research, development, manufacture and marketing of prescription
pharmaceuticals and the supply of healthcare services. It is one of the
world's leading pharmaceutical companies with healthcare sales of $26.47
billion and leading positions in sales of gastrointestinal, cardiovascular,
neuroscience, respiratory, oncology and infection products. AstraZeneca is
listed in the Dow Jones Sustainability Index (Global) as well as the
FTSE4Good Index.
In the United States, AstraZeneca is a $12.44 billion healthcare
business with more than 12,000 employees. For nearly three decades,
AstraZeneca has offered drug assistance programs side by side with its
medicines, and over the past five years, has provided over $3 billion in
savings to more than 1 million patients throughout the US and Puerto Rico.
AstraZeneca has been named one of the "100 Best Companies for Working
Mothers" by Working Mother magazine and is the only large pharmaceutical
company named to FORTUNE magazine's 2007 list of "100 Best Companies to
Work For." In 2006, for the fifth consecutive year, Science magazine named
AstraZeneca a "Top Employer" on its ranking of the world's most respected
biopharmaceutical employers.
For more information about AstraZeneca, please visit:
http://www.astrazeneca-us.com.
The statements herein include forward-looking statements. By their
nature, forward-looking statements and forecasts involve risk and
uncertainty. For a discussion of those risks and uncertainties please see
the company's Annual Report/Form 20-F for 2006.
References:
1. Data on file, DA-SXR-11.
2. SEROQUEL(R) Prescribing Information
3. Hirschfeld RMA, Calabrese JR, Weissman MM, et al. Screening for Bipolar
in the Community. J Clin Psychiatry. 2003; 64:53-59.
4. US Bureau of the Census. Available at:
http://www.census.gov/popest/national/asrh/NC-EST2005/NC-EST2005-02.xls.
Accessed April 2, 2007.
5. American Psychiatric Association. Diagnostic and Statistical Manual of
Mental Disorders. Fourth Edition Text Revision. Washington DC: 2000.
6. Introduction to Depression and Bipolar Disorder. Available at:
http://www.dbsalliance.org/pdfs/introbrochurec2.pdf. Accessed March 12,
2007.
7. Judd LL, Akiskal HS, Schettler PJ, et al. The Long-term Natural History
of the Weekly Symptomatic Status of Bipolar I Disorder. Arch Gen
Psychiatry. 2002; 59:530-537.
8. Judd LL, Akiskal HS, Schettler PJ, et al. A Prospective Investigation
of the Natural History of the Long-term Weekly Symptomatic Status of
Bipolar II Disorder. Arch Gen Psychiatry. 2003; 60:26 -269.
9. Hirschfeld RMA, Lewis L, Vornik LA. Perceptions and Impact of Bipolar
Disorder: How Far Have We Really Come? Results of the National
Depressive and Manic-Depressive Association 2000 Survey of Individuals
With Bipolar Disorder. J Clin Psychiatry. 2003; 64:161-174.
10. Oquendo MA, Chaudhury SR, Mann JJ. Pharmacotherapy of Suicidal
Behavior in Bipolar Disorder. Arch Suicide Res. 2005; 9(3):237-250.
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Related links:
http://www.astrazeneca-us.com
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CONTACT:
Jim Minnick, +1-302-886-5135,
jim.minnick@astrazeneca.com, or Abigail Baron, +1-302-885-3578,
abigail.baron@astrazeneca.com, both of AstraZeneca
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