FDA Advisory Committee Documents for SEROQUEL XR Available on AstraZeneca Web Site
04 April 2009 - 5:15AM
PR Newswire (US)
WILMINGTON, Del., April 3 /PRNewswire-FirstCall/ -- AstraZeneca
(NYSE: AZN) is aware that earlier today, the US Food and Drug
Administration (FDA) posted to its web site -- and subsequently
removed -- briefing documents for the April 8, 2009
Psychopharmacologic Drugs Advisory Committee (PDAC) meeting. The
PDAC meeting is scheduled to discuss the safety and efficacy data
provided in supplemental new drug applications (sNDA) for SEROQUEL
XR(R) (quetiapine fumarate) Extended-Release Tablets proposed for
the treatment of major depressive disorder (MDD) and generalized
anxiety disorder (GAD). AstraZeneca understands that some people
accessed these documents before they were removed from the FDA
site. To ensure that all investors have access to the information
contained in the previously released FDA briefing materials, the
company has now posted these documents, along with the AstraZeneca
briefing documents, to its web site. A link can be found on the
AstraZeneca homepage at http://www.astrazeneca.com/ Important
Safety Information for SEROQUEL XR SEROQUEL XR is indicated for the
treatment of acute depressive episodes associated with bipolar
disorder, acute manic or mixed episodes associated with bipolar I
disorder as monotherapy and as an adjunct to lithium or divalproex;
maintenance treatment of bipolar I disorder as adjunct therapy to
lithium or divalproex, and acute and maintenance treatment of
schizophrenia. Patients should be periodically reassessed to
determine the need for continued treatment and the appropriate
dose. 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 XR 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 XR is not approved
for use in patients under the age of 18 years. (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. 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). Clinically significant increases in cholesterol
(7%-16% for quetiapine vs. 3%-9% for placebo) and triglycerides
(8%-23% for quetiapine vs. 5%-16% for placebo) have been observed
in clinical trials. The proportion of patients in clinical trials
meeting a weight gain criterion of Greater Than or Equal To 7% of
body weight was 5%-23% for quetiapine vs. 0%-7% for placebo. 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. 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 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 XR should be discontinued in any patient if
the absolute neutrophil count is < 1000/mm3. 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. Warnings and Precautions also include the
risk of orthostatic hypotension, cataracts, seizures,
hyperprolactinemia, and possibility of suicide attempts.
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
possibility of a suicide attempt is inherent in schizophrenia, and
close supervision of high risk patients should accompany drug
therapy. The most commonly reported adverse reactions associated
with the use of SEROQUEL XR vs. placebo in clinical trials for
schizophrenia and bipolar disorder were somnolence (25%-52% vs.
10%-13%), dry mouth (12%-37% vs. 1%-7%), constipation (6-10% vs.
3-6%), dyspepsia (5-7% vs. 1-4%), dizziness (10-13% vs. 4-11%),
orthostatic hypotension (7% vs. 5%), weight gain (7% vs. 1%),
increased appetite (12% vs. 6%), fatigue (6-7% vs. 2-4%),
dysarthria (5% vs. 0%), and nasal congestion (5% vs. 1%). Please
see full Prescribing Information, including Boxed Warnings, for
SEROQUEL XR. About AstraZeneca AstraZeneca is engaged in the
research, development, manufacturing and marketing of meaningful
prescription medicines and in the supply of healthcare services.
AstraZeneca is one of the world's leading pharmaceutical companies
with global healthcare sales of $ 31.6 billion and is a leader in
gastrointestinal, cardiovascular, neuroscience, respiratory,
oncology and infectious disease medicines. In the United States,
AstraZeneca is a $13.5 billion dollar healthcare business. For more
information about AstraZeneca in the US or our AZ&Me(TM)
Prescription Savings programs, please 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.
DATASOURCE: AstraZeneca CONTACT: Kirsten Evraire, +1-302-885-0435,
, or Abigail Baron, +1-302-885-0435, , both of AstraZeneca Web
Site: http://www.astrazeneca-us.com/
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