Efficacy in Bipolar
Depression

Significant efficacy in acute depressive episodes of bipolar disorder1,2

The efficacy of SEROQUEL XR® (quetiapine fumarate) 300 mg/day in the acute treatment of depressive episodes associated with bipolar disorder was demonstrated in an 8-week randomized trial that included both patients with bipolar I and bipolar II disorder.1,2

Incidence of treatment-emergent mania, defined by YMRS* score ≥16 at 2 consecutive visits or at last visit, was low for SEROQUEL XR (4.4%) and placebo (6.4%). There were no adverse events of treatment-emergent mania or hypomania for either the SEROQUEL XR or the placebo group.1

*Young Mania Rating Scale (YMRS) is an 11-item, multiple-choice diagnostic questionnaire used to evaluate manic symptoms at baseline and over time in individuals with mania6.

Efficacy as early as Week 1 and continuing through Week 81,b

SEROQUEL XR 300 mg/day delivered significant efficacy as monotherapy in acute depressive episodes of bipolar I and bipolar II disorder as early as Week 1, continuing through Week 8 (primary end point)1

Proven Efficacy for Acute Episodes in Bipolar 1 and Bipolar 2 Disorder
  • Mean change from baseline in MADRSc Total Score at Week 8 was -17.4 with SEROQUEL XR vs -11.9 with placebo (P<0.001, primary end point) in patients with bipolar depression1
  • Patients were titrated to the recommended dose of 300 mg/day by Day 4

bData from an 8-week, multicenter, randomized, double-blind, parallel-group, placebo-controlled monotherapy trial in the treatment of patients with depressive episodes associated with bipolar I or bipolar II disorder. Patients received SEROQUEL XR 50 mg/day on Day 1; 100 mg/day on Day 2; 200 mg/day on Day 3; from Day 4 to the end of study, 300 mg/day. Baseline mean MADRS Total Score was -30.

cMontgomery-Åsberg Depression Rating Scale (MADRS) is a 10-item diagnostic questionnaire used for the evaluation of symptoms of depression in adults and for the assessment of changes in these symptoms.4

Significant improvement in depressive episodes in
patients with bipolar II disorder at Week 81,4,a

Subgroup of patients with bipolar II disorder
Improvement in acute depressive symptoms

Significant Improvement in acute Depressive Episodes in Patients with Bipolar 2 Disorder at Week 8

In a prespecified subgroup analysis at Week 8:

  • Mean change from baseline in MADRS Total Score at Week 8 for patients with bipolar II disorder receiving SEROQUEL XR was -19.3 vs -15.0 for placebo (P<0.05)4
  • Patients in the study met the DSM-IV-TR criteria for bipolar I or bipolar II disorder1
    • Patients were excluded from the study if they had a DSM-IV-TR diagnosis of another Axis I disorder that was symptomatic or had required treatment 6 months prior to enrollment

aSubgroup of data from an 8-week, multicenter, randomized, double-blind, parallel-group, placebo-controlled monotherapy trial in the treatment of patients with depressive episodes associated with bipolar I or bipolar II disorder. Prespecified analytical statistics (P-values) were not conducted for Weeks 1 through 7.

Significant improvement in depressive episodes in
patients with bipolar I disorder at Week 81,4,a

Subgroup of patients with bipolar I disorder
Improvement in acute depressive symptoms

Significant Improvement in acute Depressive Episodes in Patients with Bipolar 1 Disorder at Week 8

In a prespecified subgroup analysis at Week 8:

  • Mean change from baseline in MADRS Total Score at Week 8 for patients with bipolar I disorder receiving SEROQUEL XR was -19.7 vs -13.2 for placebo (P<0.001)4
  • Patients in the study met the DSM-IV-TR criteria for bipolar I or bipolar II disorder1
    • Patients were excluded from the study if they had a DSM-IV-TR diagnosis of another Axis I disorder that was symptomatic or had required treatment 6 months prior to enrollment

aSubgroup of data from an 8-week, multicenter, randomized, double-blind, parallel-group, placebo-controlled monotherapy trial in the treatment of patients with depressive episodes associated with bipolar I or bipolar II disorder. Prespecified analytical statistics (P values) were not conducted for Weeks 1 through 7.

Efficacy in Bipolar
Mania

SEROQUEL XR reduced manic symptoms

Extended-release SEROQUEL XR is a once-daily monotherapy proven effective for the acute treatment of both depressive and manic episodes of bipolar disorder.2

The efficacy of SEROQUEL XR in the treatment of acute manic or mixed episodes of bipolar I disorder was demonstrated based on the results of a 3-week placebo-controlled trial. In this trial, the primary rating instrument used to assess symptoms was the YMRS.2*

In patients with bipolar I disorder, SEROQUEL XR at a dose of 400 to 800 mg, given QD in the evening as monotherapy, was superior to placebo in reducing manic symptoms, as assessed by change in YMRS Total Score from baseline to Week 3.2

The YMRS*, an 11-item clinician-rated scale, ranges from 0 (no manic features) to 60 (the maximum score).6

In a clinical trial

Significant efficacy as early as Day 4 and continuing
through Week 37,8,a

Improvement in acute manic or mixed episodes of bipolar I disorder

Significant Efficacy as Early as Day 4 and Continuing Through Week 3 in acute manic or mixed episodes

bP<0.001 vs placebo.

cP<0.01 vs placebo.

LSM, least squares mean.

Baseline mean YMRS Total Score was 28.4-28.8.

  • Mean change from baseline in YMRS* Total Score at Week 3 was -14.3 with SEROQUEL XR vs -10.5% with placebo (P<0.001, primary end point) in patients with bipolar mania7,a
  • 50% reduction in mean YMRS* Total Score from baseline to Week 3 for SEROQUEL XR vs 37% for placebo7,8

*Young Mania Rating Scale (YMRS) is an 11-item, multiple-choice diagnostic questionnaire used to evaluate manic symptoms at baseline and over time in individuals with mania.

aData from a 3-week, multicenter, randomized, double-blind, placebo-controlled monotherapy trial in the treatment of patients with manic or mixed episodes associated with bipolar I disorder. Patients received SEROQUEL XR 300 mg on Day 1; SEROQUEL XR 600 mg/day on Day 2; from Day 3 to Day 22, flexible dosing from 400 mg/day to 800 mg/day. The mean dose was 604 mg/day.

1321503-2436100 Last updated 6/14

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formulary access in your area

72% of patients* are covered nationwide with no prior authorization.5†

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on Dosing

SEROQUEL XR should be dosed in the evening, eg, within 3-4 hours before bedtime.

Important Safety Information About SEROQUEL XR

Increased Mortality in Elderly Patients with Dementia-Related Psychosis: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. SEROQUEL XR is not approved for the treatment of patients with dementia-related psychosis.

Suicidal Thoughts and Behavior: Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older. In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber. SEROQUEL XR is not approved for use in pediatric patients under ten years of age.

Contraindication: Hypersensitivity to quetiapine or to any excipients in the SEROQUEL XR formulation. Anaphylactic reactions have been reported in patients treated with SEROQUEL XR.

Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-Related Psychosis: In placebo-controlled trials with risperidone, aripiprazole, and olanzapine in elderly subjects with dementia, there was a higher incidence of cerebrovascular adverse reactions (cerebrovascular accidents and transient ischemic attacks), including fatalities, compared to placebo-treated subjects. SEROQUEL XR is not approved for the treatment of patients with dementia-related psychosis.

Neuroleptic Malignant Syndrome (NMS): A potentially fatal symptom complex, sometimes referred to as NMS, has been reported in association with administration of antipsychotic drugs, including SEROQUEL XR. Rare cases of NMS have been reported with SEROQUEL XR. 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. Management should include immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, intensive symptomatic treatment, and medical monitoring, and treatment of any concomitant serious medical problems.

Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that include hyperglycemia/diabetes mellitus, dyslipidemia, and body weight gain. In some patients, a worsening of more than one of the metabolic parameters of weight, blood glucose, and lipids was observed in clinical studies. Changes in these metabolic profiles should be managed as clinically appropriate.

Hyperglycemia and Diabetes Mellitus: Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma, or death, has been reported in patients treated with atypical antipsychotics, including SEROQUEL XR. 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. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of antidiabetic treatment despite discontinuation of the suspect drug.

Dyslipidemia: Undesirable alterations in lipids have been observed with SEROQUEL XR use. Increases in total cholesterol, LDL-cholesterol and triglycerides, and decreases in HDL-cholesterol have been reported in clinical trials. Appropriate clinical monitoring is recommended, including fasting blood lipid testing at the beginning of and periodically during treatment.

Weight Gain: Increases in weight have been observed in clinical trials. Patients receiving SEROQUEL XR should receive regular monitoring of weight.

Tardive Dyskinesia (TD): 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. Although much less commonly, TD can develop after relatively brief treatment periods at low doses or even after treatment discontinuation. TD may remit, partially or completely, if antipsychotic treatment is withdrawn. SEROQUEL XR should be prescribed in a manner that is most likely to minimize the occurrence of TD, and discontinuation should be considered if signs and symptoms of TD occur.

Hypotension: SEROQUEL XR may induce orthostatic hypotension with associated dizziness, tachycardia, and syncope, especially during the initial dose titration period and should be used with caution in patients predisposed to hypotension or with known cardiovascular or cerebrovascular disease.

Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia, neutropenia, and agranulocytosis (including fatal cases), have been reported temporally related to atypical antipsychotics, including SEROQUEL XR. 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.

Cataracts: 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.

QT Prolongation: Postmarketing cases show increases in QT interval in patients who overdosed on quetiapine, in patients with concomitant illness, and in patients taking medicines known to cause electrolyte imbalance or increase the QT interval. Avoid use with drugs that increase the QT interval and in patients with risk factors for prolonged QT interval.

Seizures: SEROQUEL XR should be used cautiously in patients with a history of seizures or with conditions that potentially lower the seizure threshold (eg, Alzheimer’s dementia).

Potential for Cognitive and Motor Impairment: Since SEROQUEL XR has the potential to impair judgment, thinking, or motor skills, patients should be cautioned about performing activities requiring mental alertness, such as operating a motor vehicle or operating hazardous machinery, until they are reasonably certain that SEROQUEL XR therapy does not affect them adversely.

Body Temperature Regulation: Disruption of the body’s ability to reduce core body temperature has been attributed to antipsychotics. Appropriate care is advised for patients who may exercise strenuously, be exposed to extreme heat, receive concomitant medication with anticholinergic activity, or be subject to dehydration.

Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Use caution in patients at risk for aspiration pneumonia. Aspiration pneumonia is a common cause of morbidity and mortality in elderly patients, in particular those with advanced Alzheimer's dementia.

Warnings and Precautions Also Include: The risk of hypothyroidism, hyperprolactinemia, and discontinuation syndrome.

Common Adverse Reactions: The most commonly observed adverse reactions (incidence >5% and twice placebo) associated with the use of SEROQUEL XR versus placebo in clinical trials for all adult indications were somnolence (25%-52% vs 9%-13%), dry mouth (12%-40% vs 1%-8%), constipation (6%-11% vs 3%-6%), dizziness (10%-13% vs 4%-11%), increased appetite (2%-12% vs 0%-6%), dyspepsia (2%-7% vs 1%-4%), weight gain (3%-7% vs 0%-1%), fatigue (3%-14% vs 2%-4%), dysarthria (2%-5% vs 0%), and nasal congestion (2%-5% vs 1%).

Indications

SEROQUEL XR is indicated in adults for (1) adjunctive therapy to antidepressants in major depressive disorder; (2) acute depressive episodes in bipolar disorder; (3) acute manic or mixed episodes in bipolar I disorder, as either monotherapy or adjunct therapy to lithium or divalproex; (4) maintenance treatment of bipolar I disorder as an adjunct to lithium or divalproex; and (5) schizophrenia. Patients should be periodically reassessed to determine the need for treatment and the appropriate dose.

Please read full Prescribing Information for SEROQUEL XR including Boxed WARNINGS.

*“Patients” means all covered lives (Medicare MA, Medicare PDP, Medicare SN) at Tiers 1-3 in the US calculated by Fingertip Formulary®, as of May 2014, that do not require additional information to the health plan in order for SEROQUEL XR to be covered.

May be subject to quantity limitations.

AstraZeneca does not endorse any individual Commercial, Medicare Part D, or Medicaid Plan or Plans.

REFERENCES:

1. Suppes T, Datto C, Minkwitz M, Nordenhem A, Walker C, Darko D. Effectiveness of the extended release formulation of quetiapine as monotherapy for the treatment of acute bipolar depression. J Affect Disord. 2010;121(1-2):106-115.

2. Prescribing Information for SEROQUEL XR. AstraZeneca Pharmaceuticals LP, Wilmington, DE.

3. Data on file, 1716812, AstraZeneca Pharmaceuticals LP.

4. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382-389.

5. Data on file, 1717002, AstraZeneca Pharmaceuticals LP.

6. Fingertip Formulary®, May 2014.

7. Young RC, Biggs JT, Ziegler VE, Meyer DA. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry.1978;133:429-435.

8. Cutler AJ, Datto C, Nordenhem A, Minkwitz M, Acevedo L, Darko D. Extended-release quetiapine as monotherapy for the treatment of adults with acute mania: a randomized, double-blind, 3-week trial. Clin Ther. 2011;33(11):1643-1658.

9. Data on file, 1716904, AstraZeneca Pharmaceuticals LP.

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