WILMINGTON, Del., Nov. 16 /PRNewswire-FirstCall/ -- AstraZeneca (NYSE:
AZN) today announced that the U.S. Food and Drug Administration (FDA) has
approved once-daily SEROQUEL XR(TM) (quetiapine fumarate) Extended-Release
Tablets for maintenance treatment of schizophrenia in adult patients. On
May 17, 2007, the FDA approved SEROQUEL XR for the acute treatment of
schizophrenia in adult patients.
Schizophrenia patients experience high rates of symptom relapse, and as
a result, there is an important need for long-term treatment options for
schizophrenia to help reduce the risk of the recurrence of acute psychotic
episodes. (1,2)
In the clinical trial supporting this approval, patients with
schizophrenia who were treated with SEROQUEL XR experienced a significantly
longer time to relapse, compared with patients receiving placebo. Patients
receiving SEROQUEL XR demonstrated an 84% reduction in the relative risk of
relapse (hazard ratio 0.16; p<0.0001). Results showed the estimated risk of
relapse after six months was 14.3% in the SEROQUEL XR group versus 68.2% in
the placebo group (p<0.0001). Differences in relapse rate between active
treatment and placebo were large enough to require the study to be stopped
early. The complete results of the clinical trial appear in the November
issue of the journal Psychiatry 2007.(3)
"Today's FDA approval helps address the need for longer-term treatment
options for patients with schizophrenia," said Mark Scott, Ph.D., Executive
Director for Development, AstraZeneca. "The clinical trial results provided
compelling evidence for reducing the risk of relapse when these patients
are treated with SEROQUEL XR."
Schizophrenia is a serious brain disorder with symptoms including
distorted perceptions of reality, hallucinations and delusions, illogical
thinking, and flat or blunted emotions, affecting over 2 million American
adults -- about 1% of the population 18 years and older.(4,5)
The FDA approval for maintenance treatment of schizophrenia was based
on clinical trial results in which patients who had responded to SEROQUEL
XR for the treatment of schizophrenia for 16 weeks (n=197) were randomized
and either continued on SEROQUEL XR (n=94; 400-800 mg/day, flexibly dosed)
or were switched to placebo (n=103). The primary endpoint was the time from
randomization to psychiatric relapse (hospitalization for worsening
schizophrenia, increase in PANSS* Total score Greater Than or Equal To 30%,
Clinical Global Impression-Global Improvement [CGI-I]** score Greater Than
or Equal To 6, or need for additional antipsychotic medication to treat
psychosis).(3)
* Schizophrenic symptomatology is measured on 30-item Positive and
Negative Syndrome Scale (PANSS) scale. Each symptom was rated on a
severity scale from 1-7. PANSS positive (7 items), negative (7 items),
and general psychopathology (16 items) subscale scores were summarized
to give the PANSS total score.(8)
** The Clinical Global Impression (CGI) consists of 3 global scales or
items (Severity of Illness; Global Improvement; Efficacy Index). For
the primary endpoint of Study 004, item 2, the Global Improvement
scale, was used to evaluate patients. The Global Improvement scale
involves the physician rating total improvement whether or not, in the
physician's judgment, it is due entirely to drug treatment (1=very much
improved to 7=very much worse).(9)
The adverse reactions reported for SEROQUEL XR in the longer-term
placebo- controlled schizophrenia trial were generally consistent with
those reported in the short-term placebo-controlled schizophrenia trials.
The most common (Greater Than or Equal To 5% of patients) treatment
emergent adverse events for the SEROQUEL XR group versus placebo group in
the randomized phase were insomnia (8.5% vs 17.5%) and headache (7.4% vs
4.9%).(3,6)
Launched in 1997, SEROQUEL has been prescribed to millions of patients
worldwide. It is approved in 88 countries for the treatment of
schizophrenia, in 77 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 US 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.(3)
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%), headache (7% vs
5%), 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 Schizophrenia
Schizophrenia is a serious brain disorder with symptoms including
distorted perceptions of reality, hallucinations and delusions, illogical
thinking, and flat or blunted emotions.(4) Schizophrenia affects men and
women with equal frequency, but the first signs of schizophrenia typically
emerge earlier in men (in late teens or early twenties) compared to women
(in twenties or early thirties). Approximately 2.4 million American adults
-- about 1.1 % of the population age 18 and older -- suffer from
schizophrenia.(5) Medications are important in the management of symptoms.
While there is no cure for schizophrenia, it is a highly treatable and
manageable illness. Medications are classified into two categories --
"conventional" and "atypical" antipsychotics.(7)
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) Altamura AC, Bobo WV, Meltzer HY. Factors affecting outcome in
schizophrenia and their relevance for psychopharmacological treatment.
Int Clin Psychopharmacol. 2007;22:249-267.
(2) Robinson D, Woerner MG, Alvir JMJ, et al. Predictors of Relapse
Following Response From a First Episode of Schizophrenia or
Schizoaffective Disorder. "Arch Gen Psychiatry. 1999; 56: 241-247.
(3) Peuskens J, Trivedi J, Malyarov S, et al. Prevention of schizophrenia
relapse with extended release quetiapine fumarate dosed once daily: A
randomized, placebo-controlled trial in clinically stable patients.
Psychiatry 2007. 2007; 4(11):34-50.
(4) American Psychiatric Association. Diagnostic and Statistical Manual of
Mental Disorders (DSM-IV-TR). Fourth Edition. Arlington, VA, 2000:
299.
(5) National Alliance for the Mentally Ill: About Mental
Illness/Schizophrenia fact sheet. Reviewed by Kenneth Duckworth, MD:
February 2007. Accessed on September 24, 2007 at
http://www.nami.org/PrinterTemplate.cfm?Section=By_Illness&Template=/
TaggedPage/TaggedPageDisplay.cfm&TPLID=54&ContentID=23036&lstid=327.
(6) SEROQUEL XR(TM) Prescribing Information.
(7) National Institutes of Mental Health. The Numbers Count: Mental
Disorders in America. NIH Publication No. 06-4584. December 2006.
Accessed on September 24, 2007 at
http://www.nimh.nih.gov/publicat/numbers.cfm.
(8) Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale
(PANSS) for schizophrenia. Schizophr Bull. 1987; 13: 261-276.
(9) Guy, W. Clinical Global Impressions. ECDEU Assessment Manual for
Psychopharmacology, Revised (DHEW Publ. No. ADM 76-338). Rockville,
MD: National Institute of Mental Health; 1976: 218- 222.
SOURCE AstraZeneca
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Related links:
http://www.astrazeneca-us.com/
http://www.prnewswire.com/comp/985887.html /
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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