WILMINGTON, Del., May 14 /PRNewswire-FirstCall/ -- AstraZeneca (NYSE:
AZN) today announced that the U.S. Food and Drug Administration (FDA) has
approved SEROQUEL(R) (quetiapine fumarate tablets) for the maintenance
treatment of patients with bipolar I disorder, as adjunct therapy to
lithium or divalproex. SEROQUEL is approved by the FDA for the treatment of
schizophrenia, and is also the only single agent approved by the FDA for
the treatment of both depressive episodes in bipolar disorder and acute
manic episodes associated with bipolar I disorder. (1,2)
Considered one of the most severe forms of mental illness, bipolar
disorder currently affects about 8 million adults in the U.S.(3-5) Bipolar
I disorder is a lifelong psychiatric condition characterized by manic or
mixed mood episodes, interspersed with major depressive episodes. (6) It is
estimated that 0.4 percent to 1.6 percent of individuals will develop
bipolar I disorder in their lifetime. (6)
"This new indication for SEROQUEL marks an important milestone in the
treatment of bipolar I disorder because it provides patients with another
option over the long-term. In fact, despite the number of currently
available treatments, many patients with bipolar I disorder do not receive
effective therapy and some 20 to 30 percent of patients continue to display
residual mood symptoms of bipolar I disorder," said Mark Scott, Executive
Director, Clinical Development, SEROQUEL. "The studies showed that
SEROQUEL, with lithium or divalproex, can provide clinicians with a safe
and effective long-term treatment option that reduced the risk of relapse
of both manic and depressive mood events in bipolar I disorder."
The FDA approval was based on two multicenter, randomized,
double-blind, placebo-controlled clinical trials that evaluated SEROQUEL
when used as an adjunct therapy to lithium or divalproex in the maintenance
treatment of adult patients with bipolar I disorder (n=703, n=623
respectively). (7,8) The rigorous study design included a 12 to 36 week
stabilization phase which was followed by a longer-term, randomized,
double-blind treatment phase that had a mean duration of exposure of 213.2
days for SEROQUEL and 152.4 days for placebo. (9)
In both studies, patients with bipolar I disorder whose most recent
episode was manic, depressed, or mixed, were treated with either SEROQUEL
(flexible dosing between 400 and 800 mg per day in divided doses) plus
lithium-or-divalproex or placebo plus lithium-or-divalproex. (9) The
primary endpoint, which was time to recurrence of a depressive, manic, or
mixed mood event, was significant for SEROQUEL compared with placebo in
both studies. (9) Pooled study results indicated that patients treated with
SEROQUEL plus lithium-or-divalproex (n=646) had a risk reduction of 70%
relative to those treated with placebo plus lithium-or-divalproex (n=680)
for time to recurrence of a mood event (HR: 0.30; 95% CI: 0.24, 0.37;
p<0.001). (9) This reduction in risk was significant for both recurrence of
manic episodes (HR: 0.30; 95% CI: 0.22, 0.41; p less than 0.001) and
recurrence of depressive episodes (HR: 0.30; 95% CI: 0.23, 0.40; p less
than 0.001). The proportion of patients who relapsed when treated with
SEROQUEL was 19.3% [125/646] versus 50.4% [343/680] of patients on placebo.
(9)
Adverse events in these trials, which were monitored during both the
open-label stabilization phase and the randomized controlled-phase, were
generally consistent with those reported in short term, placebo-controlled
trials for SEROQUEL. In the pooled data of the two clinical studies, a
greater incidence of blood glucose increases to hyperglycemic levels
(Greater Than or Equal to 126mg/dL) was observed in patients randomized to
SEROQUEL plus lithium-or-divalproex than in patients randomized to placebo
plus lithium-or-divalproex. The SEROQUEL prescribing information was
updated in July 2007 to reflect the increases in blood glucose levels
observed in these trials.
"To date, long-term controlled studies of maintenance therapies have
been relatively few and typically focused on either the manic or depressive
phase of the illness, but not on both," said Mark Scott, Executive
Director, Clinical Development, SEROQUEL. "SEROQUEL is the only single
agent to offer proven efficacy in both the manic and depressive episodes in
bipolar disorder, and now has demonstrated proven efficacy as an adjunct
treatment for the maintenance treatment of bipolar I disorder."
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.
IMPORTANT SAFETY INFORMATION FOR SEROQUEL
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; maintenance
treatment of bipolar I disorder, as adjunct 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 is 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 is not approved for use in patients under the age of
18 years. 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 reactions 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 less than 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 reactions 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 reactions 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 reactions 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.
About Bipolar Disorder
Approximately eight million American adults are affected by bipolar
disorder, a serious psychiatric condition also known as manic depressive
illness. (4,5) 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. (6) 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 three times longer
than manic symptoms (10,11) Similarly, patients with bipolar II disorder
spend almost forty times longer in the depressed state than in hypomania.
(12) Bipolar disorder is often misdiagnosed as unipolar depression. This
misdiagnosis can lead to treatment that may exacerbate the disease. In
fact, many patients face up to ten years without appropriate treatment
before a correct diagnosis is made. (13) Up to 50 percent of patients with
bipolar disorder attempt suicide, and approximately 10 to 15 percent
complete suicide. (14) Bipolar Disorder is typically managed through a
treatment strategy with several phases -- including acute and maintenance
phases. In the acute phase, the aim is to improve the acute symptoms of the
patient; the maintenance treatment phase aims to reduce the risk of
recurrence of future episodes. (3,15)
About AstraZeneca
AstraZeneca is a major international healthcare business engaged in the
research, development, manufacturing and marketing of meaningful
prescription medicines and supplier for healthcare services. AstraZeneca is
one of the world's leading pharmaceutical companies with healthcare sales
of $29.55 billion and is a leader in gastrointestinal, cardiovascular,
neuroscience, respiratory, oncology and infectious disease medicines. In
the United States, AstraZeneca is a $13.35 billion dollar healthcare
business with 12,200 employees committed to improving people's lives.
AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as
well as the FTSE4Good Index.
For more information visit http://www.astrazeneca-us.com.
The statements contain herein include forward-looking statements.
Although we believe our expectations are based on reasonable assumptions,
any forward-looking statements, by their very nature, involve risks and
uncertainties and may be influenced by factors that could cause actual
outcomes and results to be materially different from those predicted. The
forward-looking statements reflect knowledge and information available at
the date of the preparation of this press release and the Company
undertakes no obligation to update these forward-looking statements.
Important factors that could cause actual results to differ materially from
those contained in forward-looking statements, certain of which are beyond
our control, include, among other things, those risk factors identified in
the Company's Annual Report/Form 20-F for 2007. Nothing contained herein
should be construed as a profit forecast.
References:
1. SEROQUEL Prescribing Information. Available at
http://www1.astrazeneca-us.com/pi/seroquel.pdf. Accessed April 23,
2008.
2. Data on File, AstraZeneca LP, DA-SER-51.
3. Shastry, BS. Bipolar disorder: an update. Neurochemistry International.
2005; 46:273-279.
4. Hirschfeld RMA, Calabrese JR, Weissman MM, et al. Screening for Bipolar
in the Community. J Clin Psychiatry. 2003; 64:53-59.
5. U.S. Bureau of the Census -- 2005. Available at:
http://www.census.gov/popest/national/asrh/NC-EST2005/NC-EST200502.xls.
Accessed April 2, 2007.
6. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,
Text Revision. Washington, DC: American Psychiatric Association; 2000:
382-392.
7. Vieta E, Eggens I, Persson I, et al. Efficacy and safety of quetiapine
in combination with lithium or divalproex as maintenance treatment for
bipolar I disorder [poster]. Presented at: The 20th European College of
Neuropsychopharmacology Congress; October 13-17, 2007; Vienna, Austria.
8. Suppes T, Liu S, Paulsson B, et al. Maintenance treatment in Bipolar I
disorder with quetiapine concomitant with lithium or divalproex: a
North American placebo-controlled, randomized multicenter trial
[poster]. Presented at the 46th Annual Meeting of the American College
of Neuropsychopharmacology; December 9-13, 2007; Boca Raton, FL, USA.
9. Brecher M, Liu S, Paulsson B. Quetiapine in the maintenance treatment
of bipolar I disorder: combined data from two long-term, phase III
studies [poster]. Presented at: the 3rd Biennial Conference of the
International Society for Bipolar Disorders; January 27-28, 2008;
Delhi, India; January 30, 2008; Agra, India.
10. Introduction to Depression and Bipolar Disorder. Available at:
http://www.dbsalliance.org/pdfs/introbrochurec2.pdf. Accessed March
12, 2007.
11. 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.
12. 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.
13. 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.
14. Oquendo MA, Chaudhury SR, Mann JJ. Pharmacotherapy of Suicidal
Behavior in Bipolar Disorder. Archives of Suicide Research. 2005;
9(3):237-250.
15. American Psychiatric Association. Practice Guideline for the Treatment
of Patients With Bipolar Disorder, Second Edition. April 2002.
http://www.psychiatryonline.com/pracGuide/loadGuidelinePdf.aspx?file=
Bipolar2ePG_05-15-06.
262387 5/08
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