Indicated for:

Schizophrenia:

• The treatment of schizophrenia in adult and pediatric patients (13-17 years of age).

Bipolar Disorder:

• The acute treatment of manic or mixed episodes associated with bipolar I disorder, both as monotherapy and as an adjunct to lithium or divalproex in adults and pediatric patients (10-17 years of age).

• The acute treatment of depressive episodes associated with bipolar disorder in adult patients.

• The maintenance treatment of bipolar I disorder, as an adjunct to lithium or divalproex in adult patients.

Adjunctive Treatment of Major Depressive Disorder (MDD):

• Use as adjunctive therapy to antidepressants for the treatment of MDD in adult patients.

Consideration should be given to a slower rate of dose titration and a lower target dose in the elderly and in patients who are debilitated or who have a predisposition to hypotensive reactions.

Increases in systolic and diastolic blood pressure occurred in children and adolescents and did not occur in adults.

Patients with hepatic impairment should be started on SEROQUEL XR 50 mg/day.

Elderly patients should be started on SEROQUEL XR 50 mg/day and the dose can be increased in increments of 50 mg/day depending on the clinical response and tolerability of the individual patient.

Patients who are currently being treated with SEROQUEL (immediate release formulation) may be switched to SEROQUEL XR at the equivalent total daily dose taken once daily.

SEROQUEL XR is not approved for use in pediatric patients under ten years of age.

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.

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.

Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment.

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.

Atypical antipsychotic drugs have been associated with metabolic changes that include hyperglycemia, diabetes mellitus, dyslipidemia, and body weight gain. While all of the drugs in the class have been shown to produce some metabolic changes, each drug has its own specific risk profile. In some patients, a worsening of more than one of the metabolic parameters of weight, blood glucose, and lipids was observed in clinical studies.

Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics, including quetiapine.

A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs including quetiapine. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome.

Quetiapine may induce orthostatic hypotension associated with dizziness, tachycardia and, in some patients, syncope, especially during the initial dose-titration period, probably reflecting its ά1-adrenergic antagonist properties.

Quetiapine should be used with particular caution in patients with known cardiovascular disease (history of myocardial infarction or ischemic heart disease, heart failure or conduction abnormalities), cerebrovascular disease or conditions which would predispose patients to hypotension (dehydration, hypovolemia and treatment with antihypertensive medications).

Atypical antipsychotic drugs, including SEROQUEL XR, may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries.

In clinical trials and postmarketing experience, events of leukopenia/neutropenia have been reported temporally related to atypical antipsychotic agents, including quetiapine fumarate. Agranulocytosis has also been reported. Agranulocytosis has been reported with quetiapine, including fatal cases and cases in patients without pre-existing risk factors.

The development of cataracts was observed in association with quetiapine treatment in chronic dog studies. Lens changes have also been observed in adults, children, and adolescents during long-term quetiapine treatment but a causal relationship to quetiapine use has not been established. Nevertheless, the possibility of lenticular changes cannot be excluded at this time.

As with other antipsychotics, quetiapine fumarate should be used cautiously in patients with a history of seizures or with conditions that potentially lower the seizure threshold, e.g., Alzheimer’s dementia. Conditions that lower the seizure threshold may be more prevalent in a population of 65 years or older.

Clinical trials with quetiapine demonstrated dose-related decreases in thyroid hormone levels.

Like other drugs that antagonize dopamine D2 receptors, SEROQUEL XR elevates prolactin levels in some patients and the elevation may persist during chronic administration. Hyperprolactinemia, regardless of etiology, may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients.

Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds. Long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both female and male subjects.

Disruption of the body’s ability to reduce core body temperature has been attributed to antipsychotic agents. Appropriate care is advised when prescribing SEROQUEL XR for patients who will be experiencing conditions which may contribute to an elevation in core body temperature, e.g., exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity, or being subject to dehydration.

Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Aspiration pneumonia is a common cause of morbidity and mortality in elderly patients, in particular those with advanced Alzheimer’s dementia. SEROQUEL XR and other antipsychotic drugs should be used cautiously in patients at risk for aspiration pneumonia.

Acute withdrawal symptoms, such as insomnia, nausea and vomiting have been described after abrupt cessation of atypical antipsychotic drugs, including quetiapine fumarate.

Constipation was a commonly reported adverse event in patients treated with quetiapine and represents a risk factor for intestinal obstruction. Intestinal obstruction has been reported with quetiapine, including fatal reports in patients who were receiving multiple concomitant medications that decrease intestinal motility.

SEROQUEL XR should be used with caution in patients with a current diagnosis or prior history of urinary retention, clinically significant prostatic hypertrophy, or constipation, or increased intraocular pressure.

Since quetiapine 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 (including automobiles) or operating hazardous machinery until they are reasonably certain that quetiapine therapy does not affect them adversely. Somnolence may lead to falls.

The use of quetiapine should be avoided in combination with other drugs that are known to prolong QTc including Class 1A antiarrhythmics (e.g., quinidine, procainamide) or Class III antiarrhythmics (e.g., amiodarone, sotalol), antipsychotic medications (e.g., ziprasidone, chlorpromazine, thioridazine), antibiotics (e.g., gatifloxacin, moxifloxacin), or any other class of medications known to prolong the QTc interval (e.g., pentamidine, levomethadyl acetate, methadone).

Quetiapine should also be avoided in circumstances that may increase the risk of occurrence of torsade de pointes and/or sudden death including (1) a history of cardiac arrhythmias such as bradycardia; (2) hypokalemia or hypomagnesemia; (3) concomitant use of other drugs that prolong the QTc interval; and (4) presence of congenital prolongation of the QT interval.

Caution should also be exercised when quetiapine is prescribed in patients with increased risk of QT prolongation (e.g., cardiovascular disease, family history of QT prolongation, the elderly, congestive heart failure and heart hypertrophy).

Norquetiapine, an active metabolite of quetiapine, has moderate to strong affinity for several muscarinic receptor subtypes. This contributes to anticholinergic adverse reactions when SEROQUEL XR is used at therapeutic doses, taken concomitantly with other anticholinergic medications, or taken in overdose.

SEROQUEL XR dose should be reduced to one sixth of original dose when co-medicated with a potent CYP3A4 inhibitor (e.g., ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.). When the CYP3A4 inhibitor is discontinued, the dose of SEROQUEL XR should be increased by 6 fold.

SEROQUEL XR dose should be increased up to 5 fold of the original dose when used in combination with a chronic treatment (e.g., greater than 7-14 days) of a potent CYP3A4 inducer (e.g., phenytoin, carbamazepine, rifampin, avasimibe, St. John’s wort etc.). The dose should be titrated based on the clinical response and tolerance of the individual patient. When the CYP3A4 inducer is discontinued, the dose of SEROQUEL XR should be reduced to the original level within 7­ 14 days.

Given the primary CNS effects of SEROQUEL XR, caution should be used when it is taken in combination with other centrally acting drugs.

Quetiapine potentiated the cognitive and motor effects of alcohol in a clinical trial in subjects with selected psychotic disorders, and alcoholic beverages should be limited while taking quetiapine.

Because of its potential for inducing hypotension, SEROQUEL XR may enhance the effects of certain antihypertensive agents.

SEROQUEL XR may antagonize the effects of levodopa and dopamine agonists.

There are no adequate and well-controlled studies of SEROQUEL XR use in pregnant women. Animal studies: embryo-fetal toxicity.

SEROQUEL XR was excreted into human milk. Because of the potential for serious adverse reactions in nursing infants from SEROQUEL XR, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother’s health.

GoToSource

• Use in patients under the age of 10 for bipolar disorder. GoToSource

• Use in patients under the age of 13 for schizophrenia. GoToSource

• Use in patients under the age of 18 for maintenance treatment of schizophrenia, bipolar depression, maintenance treatment of bipolar disorder, or treatment of major depressive disorder. GoToSource

• Generalized anxiety disorder, dementia, obsessive compulsive disorders and psychotic symptoms in patients with parkinson’s disease. GoToSource

• Aggression in autistic spectrum disorder and other pervasive developmental disorders. GoToSource

• Prevention of refractory migraines. GoToSource

• Symptoms of alzheimer’s disease. GoToSource

• Panic attacks and post‑traumatic stress disorder. GoToSource

• Monotherapy for maintenance treatment of bipolar disorder. GoToSource

• Tourette syndrome. GoToSource

Weight gain and hyperlipidemia (elevated lipid/fat levels in blood). GoToSource

Restless legs syndrome. GoToSource

Akathisia (movement disorder). GoToSource

Constipation, postural hypotension, bone marrow suppression and liver failure. GoToSource

Sleep-related eating disorders and somnambulism (sleep walking). GoToSource

New-onset type 2 diabetes. GoToSource

Hypothyroidism (underactive thyroid). GoToSource

Prolonged QT and sudden cardiac death. GoToSource

Increased risk of death in elderly patients with dementia-related psychosis. GoToSource

Stevens-johnson syndrome, toxic epidermal necrolysis and erythroderma (potentially fatal skin reaction). GoToSource

Neuroleptic malignant syndrome (life-threatening neurological disorder). GoToSource

Rhabdomyolysis (breakdown of muscle fibers). GoToSource

Tardive dyskinesia. GoToSource

Manic episodes. GoToSource

Interaction with general anesthesia causing refractory hypotension. GoToSource

Hypocortisolism (adrenal insufficiency). GoToSource

Ischemic strokes. GoToSource 

Leukopenia (decreased number of white blood cells in blood) and neutropenia (low levels of neutrophils in blood). GoToSource

Development of cataracts. GoToSource

Seizures. GoToSource

Hyperprolactinemia (high levels of prolactin in the blood, a hormone secreted by the pituitary gland). GoToSource

Dysphagia (difficulty swallowing). GoToSource

Discontinuation syndrome. GoToSource

Drug rash with eosinophilia and systemic symptoms (life-threatening hypersensitivity reaction). GoToSource

Edema (swelling). GoToSource 

Suicidality and suicidal ideation. GoToSource

Lawsuits filed for diabetes, neuroleptic malignant syndrome and tardive dyskinesia.