Quetiapine

SEROQUEL is an atypical antipsychotic indicated for the treatment of: • Schizophrenia. • Bipolar I disorder manic episodes. • Bipolar disorder, depressive episodes

The mechanism of action of quetiapine in the listed indications is unclear. However, the efficacy of quetiapine in these indications could be mediated through a combination of dopamine type 2 (D 2 ) and serotonin type 2 (5HT 2 ) antagonism. The active metabolite, N-desalkyl quetiapine (norquetiapine), has similar activity at D 2, but greater activity at 5HT 2A receptors, than the parent drug (quetiapine).

• SEROQUEL can be taken with or without food. Indication Initial Dose Recommended Dose Maximum Dose Schizophrenia - Adults 25 mg twice daily 150-750 mg/day 750 mg/day Schizophrenia - Adolescents (13-17 years) 25 mg twice daily 400-800 mg/day 800 mg/day Bipolar Mania - Adults Monotherapy or as an adjunct to lithium or divalproex 50 mg twice daily 400-800 mg/day 800 mg/day Bipolar Mania - Children and Adolescents (10-17 years), Monotherapy 25 mg twice daily 400-600 mg/day 600 mg/day Bipolar Depression - Adults 50 mg once daily at bedtime 300 mg/day 300 mg/day • Geriatric Use: Consider a lower starting dose (50 mg/day), slower titration and careful monitoring during the initial dosing period in the elderly. • Hepatic Impairment: Lower starting dose (25 mg/day) and slower titration may be needed

Hypersensitivity to quetiapine or to any excipients in the SEROQUEL formulation. Anaphylactic reactions have been reported in patients treated with SEROQUEL. Known hypersensitivity to SEROQUEL or any components in the formulation.

Boxed warning: 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 is not approved for the treatment of patients with dementia-related psychosis. • Cerebrovascular Adverse Reactions: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack) has been seen in elderly patients with dementia-related psychoses treated with atypical antipsychotic drugs. • Neuroleptic Malignant Syndrome (NMS): Manage with immediate discontinuation and close monitoring. • Metabolic Changes: Atypical antipsychotics have been associated with metabolic changes.

The following adverse reactions are discussed in more detail in other sections of the labeling: • Increased mortality in elderly patients with dementia-related psychosis • Suicidal thoughts and behaviors in adolescents and young adults • Cerebrovascular adverse reactions, including stroke in elderly patients with dementia-related psychosis • Neuroleptic Malignant Syndrome (NMS) • Metabolic changes (hyperglycemia, dyslipidemia, weight gain) • Tardive dyskinesia • Hypotension • Falls • Increases in blood pressure (children and adolescents) • Leukopenia, neutropenia and agranulocytosis • Cataracts • QT Prolongation • Seizures • Hypothyroidism • Hyperprolactinemia • Potential for cognitive and motor impairment • Body temperature regulation • Dysphagia • Discontinuation Syndrome • Anticholinergic (antimuscarinic) Effects Most common adverse reactions (incidence ≥5% and twice placebo): Adults: somnolence, dry mouth, dizziness, constipation, asthenia, abdominal pain, postural hypotension, pharyngitis, weight gain, lethargy, ALT increased, dyspepsia.

• Concomitant use of strong CYP3A4 inhibitors: Reduce quetiapine dose to one sixth when coadministered with strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir). • Concomitant use of strong CYP3A4 inducers: Increase quetiapine dose up to 5 fold when used in combination with a chronic treatment (more than 7-14 days) of potent CYP3A4 inducers (e.g., phenytoin, rifampin, St. John’s wort). • Discontinuation of strong CYP3A4 inducers: Reduce quetiapine dose by 5-fold within 7-14 days of discontinuation of CYP3A4 inducers

Store at 25ºC (77ºF), excursions permitted to 15-30ºC (59-86ºF).