HIGHLIGHTS OF PRESCRIBING INFORMATION Major Depressive 50 mg/day 150-300 mg/day 300 mg/day These highlights do not include all the information needed to use Disorder, Adjunctive SEROQUEL XR safely and effectively. See full prescribing information Therapy with for SEROQUEL XR. Antidepressants - SEROQUEL XR® (quetiapine fumarate) extended-release tablets, for Adults (2.2) oral use Initial U.S. Approval: 1997 --------------------- DOSAGE FORMS AND STRENGTHS -------------------- Extended-Release Tablets: 50 mg, 150 mg, 200 mg, 300 mg, and 400 mg (3) WARNING: INCREASED MORTALITY IN ELDERLY ------------------------------ CONTRAINDICATIONS ----------------------------- PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS; and Known hypersensitivity to SEROQUEL XR or any components in the SUICIDAL THOUGHTS AND BEHAVIORS formulation. (4) See full prescribing information for complete boxed warning. Increased Mortality in Elderly Patients with Dementia-Related ----------------------- WARNINGS AND PRECAUTIONS ---------------------- Psychosis Cerebrovascular Adverse Reactions: Increased incidence of Elderly patients with dementia-related psychosis treated with cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack) antipsychotic drugs are at an increased risk of death. has been seen in elderly patients with dementia-related psychoses treated SEROQUEL XR is not approved for elderly patients with with atypical antipsychotic drugs (5.3) dementia-related psychosis. (5.1) Neuroleptic Malignant Syndrome (NMS): Manage with immediate Suicidal Thoughts and Behaviors discontinuation and close monitoring (5.4) Increased risk of suicidal thoughts and behavior in children, Metabolic Changes: Atypical antipsychotics have been associated with adolescents and young adults taking antidepressants. (5.2) metabolic changes. These metabolic changes include hyperglycemia, Monitor for worsening and emergence of suicidal thoughts and dyslipidemia, and weight gain (5.5) behaviors. (5.2) Hyperglycemia and Diabetes Mellitus: Monitor patients for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Monitor glucose regularly in -------------------------- RECENT MAJOR CHANGES -------------------------- patients with diabetes or at risk for diabetes Warnings and Precautions, Leukopenia, Neutropenia and Dyslipidemia: Undesirable alterations have been observed in Agranulocytosis (5.10) 11/2018 patients treated with atypical antipsychotics. Appropriate clinical monitoring is recommended, including fasting blood Warnings and Precautions, Anticholinergic lipid testing at the beginning of, and periodically, during (antimuscarinic) Effects (5.20) 11/2018 treatment Weight Gain: Gain in body weight has been observed; --------------------------- INDICATIONS AND USAGE -------------------------- clinical monitoring of weight is recommended SEROQUEL XR is an atypical antipsychotic indicated for the treatment of: Tardive Dyskinesia: Discontinue if clinically appropriate (5.6) Schizophrenia (1.1) Hypotension: Use with caution in patients with known cardiovascular or Bipolar I disorder, manic or mixed episodes (1.2) cerebrovascular disease (5.7) Bipolar disorder, depressive episodes (1.2) Increased Blood Pressure in Children and Adolescents: Monitor blood Major depressive disorder, adjunctive therapy with antidepressants pressure at the beginning of, and periodically during treatment in (1.3) children and adolescents (5.9) Leukopenia, Neutropenia and Agranulocytosis: Monitor complete blood ---------------------- DOSAGE AND ADMINISTRATION ---------------------- count frequently during the first few months of treatment in patients with Swallow tablets whole and do not split, chew or crush (2.1) a pre-existing low white cell count or a history of Take without food or with a light meal (approx. 300 calories) (2.1) leukopenia/neutropenia and discontinue SEROQUEL XR at the first Administer once daily, preferably in the evening (2.1) sign of a decline in WBC in absence of other causative factors (5.10) Cataracts: Lens changes have been observed in patients during long­ Geriatric Use: Consider a lower starting dose (50 mg/day), slower term quetiapine treatment. Lens examination is recommended when titration, and careful monitoring during the initial dosing period in the elderly. (2.3, 8.5) starting treatment and at 6-month intervals during chronic treatment (5.11) Hepatic Impairment: Lower starting dose (50 mg/day) and slower Anticholinergic(antimuscarinic) Effects: Use with caution with other titration may be needed (2.4, 8.7, 12.3) anticholinergic drugs and in patients with urinary retention, prostatic Indication Initial Recommended Maximum hypertrophy, constipation, or increased intraocular pressure (5.20). Dose Dose Dose Schizophrenia ­ 300 400-800 mg/day 800 mg/day ------------------------------ ADVERSE REACTIONS ----------------------------- Adults (2.2) mg/day Most common adverse reactions (incidence ≥5% and twice placebo): Schizophrenia ­ 50 mg/day 400-800 mg/day 800 mg/day Adults: somnolence, dry mouth, constipation, dizziness, increased appetite, Adolescents (13 to dyspepsia, weight gain, fatigue, dysarthria, and nasal congestion (6.1) 17 years) (2.2) Children and Adolescents: somnolence, dizziness, fatigue, increased appetite, Bipolar I Disorder 300 400-800 mg/day 800 mg/day nausea, vomiting, dry mouth, tachycardia, weight increased (6.1) manic or mixed ­ mg/day To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca Acute monotherapy at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. or adjunct to lithium or divalproex ­ ------------------------------ DRUG INTERACTIONS ----------------------------- Adults (2.2) Concomitant use of strong CYP3A4 inhibitors: Reduce quetiapine dose Bipolar I Disorder, 50 mg/day 400-600 mg/day 600 mg/day to one sixth when coadministered with strong CYP3A4 inhibitors (e.g., manic Acute ketoconazole, ritonavir) (2.5, 7.1, 12.3) monotherapy ­ Concomitant use of strong CYP3A4 inducers: Increase quetiapine dose Children and up to 5 fold when used in combination with a chronic treatment (more Adolescents (10 to than 7-14 days) of potent CYP3A4 inducers (e.g., phenytoin, rifampin, 17 years) (2.2) St. John’s wort) (2.6, 7.1, 12.3) Bipolar Disorder, 50 mg/day 300 mg/day 300 mg/day Discontinuation of strong CYP3A4 inducers: Reduce quetiapine dose Depressive Episodes by 5 fold within 7-14 days of discontinuation of CYP3A4 inducers - Adults (2.2) (2.6, 7.1, 12.3) 1 Reference ID: 4356288 ----------------------- USE IN SPECIFIC POPULATIONS ---------------------- See 17 for PATIENT COUNSELING INFORMATION and Medication Pregnancy: Limited human data. Based on animal data, may cause fetal Guide harm. Quetiapine should be used only if the potential benefit justifies Revised: 11/2018 the potential risk (8.1) Nursing Mothers: Discontinue drug or nursing, taking into consideration importance of drug to mother’s health (8.3) FULL PRESCRIBING INFORMATION: CONTENTS* WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS 5.18 Dysphagia WITH DEMENTIA-RELATED PSYCHOSIS; AND SUICIDAL 5.19 Discontinuation Syndrome THOUGHTS AND BEHAVIORS 5.20 Anticholinergic (antimuscarinic) Effects 1 INDICATIONS AND USAGE 6 ADVERSE REACTIONS 1.1 Schizophrenia 6.1 Clinical Studies Experience 1.2 Bipolar Disorder 6.2 Postmarketing Experience 1.3 Adjunctive Treatment of Major Depressive Disorder (MDD) 7 DRUG INTERACTIONS 1.4 Special Considerations in Treating Pediatric Schizophrenia and Bipolar 7.1 Effect of Other Drugs on Quetiapine I Disorder 7.2 Effect of Quetiapine on Other Drugs 2 DOSAGE AND ADMINISTRATION 8 USE IN SPECIFIC POPULATIONS 2.1 Important Administration Instructions 8.1 Pregnancy 2.2 Recommended Dosing 8.2 Labor and Delivery 2.3 Dose Modifications in Elderly Patients 8.3 Nursing Mothers 2.4 Dose Modifications in Hepatically Impaired Patients 8.4 Pediatric Use 2.5 Dose Modifications when used with CYP3A4 Inhibitors 8.5 Geriatric Use 2.6 Dose Modifications when used with CYP3A4 Inducers 8.6 Renal Impairment 2.7 Re-initiation of Treatment in Patients Previously Discontinued 8.7 Hepatic Impairment 2.8 Switching Patients from SEROQUEL Tablets to SEROQUEL XR 9 DRUG ABUSE AND DEPENDENCE Tablets 9.1 Controlled Substance 2.9 Switching from Antipsychotics 9.2 Abuse 3 DOSAGE FORMS AND STRENGTHS 10 OVERDOSAGE 4 CONTRAINDICATIONS 10.1 Human Experience 5 WARNINGS AND PRECAUTIONS 10.2 Management of Overdosage 5.1 Increased Mortality in Elderly Patients with Dementia-Related 11 DESCRIPTION Psychosis 12 CLINICAL PHARMACOLOGY 5.2 Suicidal Thoughts and Behaviors in Adolescents and Young Adults 12.1 Mechanism of Action 5.3 Cerebrovascular Adverse Reactions, Including Stroke, in Elderly 12.2 Pharmacodynamics Patients with Dementia-Related Psychosis 12.3 Pharmacokinetics 5.4 Neuroleptic Malignant Syndrome (NMS) 13 NONCLINICAL TOXICOLOGY 5.5 Metabolic Changes 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 5.6 Tardive Dyskinesia 13.2 Animal Toxicology and/or Pharmacology 5.7 Hypotension 14 CLINICAL STUDIES 5.8 Falls 14.1 Schizophrenia 5.9 Increases in Blood Pressure (Children and Adolescents) 14.2 Bipolar Disorder 5.10 Leukopenia, Neutropenia and Agranulocytosis 14.3 Major Depressive Disorder, Adjunctive Therapy to Antidepressants 5.11 Cataracts 16 HOW SUPPLIED/STORAGE AND HANDLING 5.12 QT Prolongation 17 PATIENT COUNSELING INFORMATION 5.13 Seizures 17.1 Information for Patients 5.14 Hypothyroidism MEDICATION GUIDE 5.15 Hyperprolactinemia 5.16 Potential for Cognitive and Motor Impairment 5.17 Body Temperature