openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
boxed warning
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS See full prescribing information for complete boxed warning. • Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Olanzapine is not approved for the treatment of patients with dementia-related psychosis. ( 5.1 , 8.5 , 17 ) When using olanzapine and fluoxetine in combination, also refer to the Boxed Warning section of the package insert for Symbyax. 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. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Olanzapine is not approved for the treatment of patients with dementia-related psychosis [see Warnings and Precautions ( 5.1 ), Use in Specific Populations ( 8.5 ), and Patient Counseling Information ( 17 )] . When using olanzapine and fluoxetine in combination, also refer to the Boxed Warning section of the package insert for Symbyax.
openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
warnings and cautions
5 WARNINGS AND PRECAUTIONS Elderly Patients with Dementia-Related Psychosis: Increased risk of death and increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack). ( 5.1 ) Suicide: The possibility of a suicide attempt is inherent in schizophrenia and in bipolar I disorder, and close supervision of high-risk patients should accompany drug therapy; when using in combination with fluoxetine, also refer to the Boxed Warning and Warnings and Precautions sections of the package insert for Symbyax.( 5.2 ) Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring. ( 5.3 ) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Discontinue if DRESS is suspected. ( 5.4 ) Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes including hyperglycemia, dyslipidemia, and weight gain. ( 5.5 ) Hyperglycemia and Diabetes Mellitus: In some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients taking olanzapine. Patients taking olanzapine should be monitored for symptoms of hyperglycemia and undergo fasting blood glucose testing at the beginning of, and periodically during, treatment. ( 5.5 ) Dyslipidemia: Undesirable alterations in lipids have been observed. Appropriate clinical monitoring is recommended, including fasting blood lipid testing at the beginning of, and periodically during, treatment. ( 5.5 ) Weight Gain: Potential consequences of weight gain should be considered. Patients should receive regular monitoring of weight. ( 5.5 ) Tardive Dyskinesia: Discontinue if clinically appropriate. ( 5.6 ) Orthostatic Hypotension: Orthostatic hypotension associated with dizziness, tachycardia, bradycardia and, in some patients, syncope, may occur especially during initial dose titration. Use caution in patients with cardiovascular disease, cerebrovascular disease, and those conditions that could affect hemodynamic responses. ( 5.7 ) Leukopenia, Neutropenia, and Agranulocytosis: Has been reported with antipsychotics, including olanzapine. Patients with a history of a clinically significant low white blood cell count (WBC) or drug induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and discontinuation of olanzapine should be con...
warnings and cautions table
Table 2: Changes in Fasting Glucose Levels from Adult Olanzapine Monotherapy Studies a Not Applicable. Up to 12 weeks exposure At least 48 weeks exposure LaboratoryAnalyte Category Change (at least once) from Baseline Treatment Arm N Patients N PatientsNormal to HighOlanzapine5432.2%34512.8%Fasting(<100 mg/dL to ≥126 mg/dL)Placebo2933.4%NA aNA aGlucoseBorderline to High (≥100 mg/dL and <126 mg/dL Olanzapine17817.4%12726.0%to ≥126 mg/dL)Placebo9611.5%NA aNA a
openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
adverse reactions
6 ADVERSE REACTIONS Most common adverse reactions (≥5% and at least twice that for placebo) associated with: Oral Olanzapine Monotherapy: • Schizophrenia (Adults) – postural hypotension, constipation, weight gain, dizziness, personality disorder, akathisia ( 6.1 ) • Schizophrenia (Adolescents) – sedation, weight increased, headache, increased appetite, dizziness, abdominal pain, pain in extremity, fatigue, dry mouth ( 6.1 ) • Manic or Mixed Episodes, Bipolar I Disorder (Adults) – asthenia, dry mouth, constipation, increased appetite, somnolence, dizziness, tremor. ( 6.1 ) • Manic or Mixed Episodes, Bipolar I Disorder (Adolescents) – sedation, weight increased, increased appetite, headache, fatigue, dizziness, dry mouth, abdominal pain, pain in extremity. ( 6.1 ). Combination of Olanzapine and Lithium or Valproate: • Manic or Mixed Episodes, Bipolar I Disorder (Adults) – dry mouth, weight gain, increased appetite, dizziness, back pain, constipation, speech disorder, increased salivation, amnesia, paresthesia. ( 6.1 ) Olanzapine and Fluoxetine in Combination: Also refer to the Adverse Reactions section of the package insert for Symbyax. ( 6 ) To report SUSPECTED ADVERSE REACTIONS , contact Torrent Pharma Inc. at 1-800-912-9561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch When using olanzapine and fluoxetine in combination, also refer to the Adverse Reactions section of the package insert for Symbyax. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect or predict the rates observed in practice. Clinical Trials in Adults The information below for olanzapine is derived from a clinical trial database for olanzapine consisting of 10,504 adult patients with approximately 4,765 patient-years of exposure to olanzapine. This database includes: (1) 2,500 patients who participated in multiple-dose oral olanzapine premarketing trials in schizophrenia and Alzheimer's disease representing approximately 1,122 patient-years of exposure as of February 14, 1995; (2) 182 patients who participated in oral olanzapine premarketing bipolar I disorder (manic or mixed episodes) trials representing approximately 66 patient-years of exposure; (3) 191 patients who participa...
adverse reactions table
Table 9: Common Treatment-Emergent Adverse Reactions Associated with theUse of Oral Olanzapine in 6-Week Trials — SCHIZOPHRENIA a Personality disorder is the COSTART term for designating nonaggressive objectionable behavior. Percentage of Patients Reporting Event Adverse Reaction Olanzapine (N=248) Placebo (N=118)Postural hypotension52Constipation93Weight gain61Dizziness114Personality disorder a84Akathisia51