Weight Changes
Some patients may experience weight gain with SEROQUEL and SEROQUEL XR.
- In pivotal trials of all approved indications, when weight gain was defined as an increase in weight of 7% or more from baseline, the incidence was 8% to 23% in patients receiving SEROQUEL or SEROQUEL XR vs 2% to 7% in patients receiving placebo1,2
- Patients with bipolar depression treated with SEROQUEL 300 mg (n=283) and SEROQUEL 600 mg (n=271) experienced a mean weight gain of 1.2 kg and 1.5 kg, respectively, after 8 weeks of treatment*3
- Patients with acute bipolar mania treated with SEROQUEL† monotherapy (n=209) experienced a mean weight gain of 1.8 kg after 12 weeks of treatment*4
- Patients with schizophrenia treated with SEROQUEL XR (300–800 mg/day) (n=920) experienced a mean weight gain of 1.27 kg after 6 weeks of treatment*5
- Based on a retrospective analysis of patients with schizophrenia treated with SEROQUEL monotherapy‡6,7:
- Mean weight gain was 3.59 kg after 52 weeks of treatment (n=297)6
- Most of the weight gain occurred in the first 12 weeks of treatment6,7
*Last observation carried forward.
†In pivotal mania trials, the average dose in responders (patients with ≥50% improvement in Young Mania Rating Scale total score) was 600 mg/day.
‡Based on retrospective analysis of data from patients with schizophrenia treated with SEROQUEL from the SEROQUEL Clinical Trials Database, 1993-1999.
Hyperglycemia
Important Safety Information for SEROQUEL and SEROQUEL XR
SEROQUEL XR is indicated for the acute and maintenance treatment of schizophrenia. SEROQUEL is indicated for the treatment of depressive episodes in bipolar disorder; acute manic episodes in bipolar I disorder, as either monotherapy or adjunct therapy to lithium or divalproex; for the maintenance treatment of bipolar I disorder as adjunct therapy to lithium or divalproex; and 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 and SEROQUEL XR are 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 and SEROQUEL XR are not approved for use in patients under the age of 18 years. SEROQUEL XR is not approved for the treatment of depression; however, SEROQUEL is approved for the treatment of bipolar depression. (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
- 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 and 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 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, hyperlipidemia, 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 observed adverse reactions associated with the use of SEROQUEL XR versus placebo in clinical trials for schizophrenia and bipolar disorder 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%).
- In long-term clinical trials of quetiapine, hyperglycemia (fasting glucose ≥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)
Please see Prescribing Information for SEROQUEL and SEROQUEL XR, including Boxed Warnings.
REFERENCES:
- SEROQUEL Prescribing Information, AstraZeneca Pharmaceuticals LP.
- SEROQUEL XR Prescribing Information, AstraZeneca Pharmaceuticals LP.
- Data on file, DA-SER-46, AstraZeneca Pharmaceuticals LP.
- Vieta E, Mullen J, Brecher M, et al. Quetiapine monotherapy for mania associated with bipolar disorder: combined analysis of two international, double-blind, randomised, placebo-controlled studies.
Curr Med Res Opin. 2005;21(5):923-934.
- Data on file, DA-SXR-05, AstraZeneca Pharmaceuticals LP.
- Brecher M, Leong RW, Stening G, et al. Quetiapine and long-term weight change: a comprehensive data review of patients with schizophrenia. J Clin Psychiatry. 2007;68:597-603.
- Data on file, DA-SER-44, AstraZeneca Pharmaceuticals LP.