FDA label 4706fe96-ccf0-6a85-e054-00144ff8d46c

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 , 5.14 ) and Patient Counseling Information ( 17.2 )]. When using olanzapine and fluoxetine in combination, also refer to the Boxed Warning of the package insert for olanzapine and fluoxetine in combination. 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, 5.14, 17.2) When using olanzapine and fluoxetine in combination, also refer to the Boxed Warning section of the package insert for olanzapine and fluoxetine in combination.

WARNINGS AND PRECAUTIONS 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 olanzapine and fluoxetine in combination. (5.2). Neuroleptic Malignant Syndrome: manage with immediate discontinuation and close monitoring (5.3) Hyperglycemia: 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 (5.4)Hyperlipidemia: Undesirbale 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 monitor of weight (5.6) Tardive Dyskinesia: Discontinue if clinically appropriate (5.7) 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 (5.8) 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 planzapine should be considered at the first sign of a clinically significant decline in WBC in the absence of other causative factors (5.9) Seizures: Use cautiously in patients with history of seizures or with conditions that potentially lower the seizure threshold (5.11) Potential for Cognitive and Motor Impairment: has potential to impair judgement, thinking, and motor skills. Use caution when operating machinery (5.12) Hyperprolactinemia: may elevate prolactin levels (5.1) Use in Combination of Fluoxetine, Lithium or Valproate: Also refer to the package inserts of olanzapine and fluoxetine in combination, lithium or valporate (5.16) Laboratory Tests: Monitor fasting blood glucose and lipid profiles at the beginning of, and periodically during, treatment (5.17)

ADVERSE REACTIONS ADVERSE REACTIONS Most common adverse reactions (greater than less than 5% and at least twice of 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 appetitie, dizziness, abdominal pain, pain in extermity, fatigue, dry mouth (6.1) Manic or Mixed Episodes, Bipolar I Disorder (Adults) - asthenia, dry mouth, weight gain, increased appetite, dizziness, back pain, constipation, speech disorder, increased salication, amnesia, parethesia (6.1) Olanzapine and Fluozetine in Combination: Also refer to the Adverse refer to the Adverse reactions section of the package insert for olanzapine and fluoxetine in combination (6) To report SUSPECTED ADVERSE REACTIONS, contact Teva USA, Pharmacovigilance at 1-888-838-2872 x6351 or drug.safety@tevausa.com; or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch