Olanzapine: uses, appearance and warnings

Olanzapine is an atypical antipsychotic indicated: As oral formulation for the: • Treatment of schizophrenia. ( 1.1 ) Adults: Efficacy was established in three clinical trials in patients with schizophrenia: two 6-week trials and one maintenance trial. ( 14.1 ) Adolescents (ages 13 to 17): Efficacy was established in one 6week trial in patients with schizophrenia (14.1) . The increased potential (in adolescents compared with adults) for weight gain and dyslipidemia may lead clinicians to consider prescribing other drugs first in adolescents. (1.1) • Acute treatment of manic or mixed episodes associated with bipolar I disorder and maintenance treatment of bipolar I disorder. ( 1.2 ) Adults: Efficacy was established in three clinical trials in patients with manic or mixed episodes of bipolar I disorder: two 3- to 4-week trials and one maintenance trial. ( 14.2 ) Adolescents (ages 13 to 17): Efficacy was established in one 3-week trial in patients with manic or mixed episodes associated with bipolar I disorder (14.2) . The increased potential (in adolescents compared with adults) for weight gain and dyslipidemia may lead clinicians to consider prescribing other drugs first in adolescents. (1.2) Medication therapy for pediatric patients with schizophrenia or bipolar I disorder should be undertaken only after a thorough diagnostic evaluation and with careful consideration of the potential risks. (1.3) Adjunct to valproate or lithium in the treatment of manic or mixed episodes associated with bipolar I disorder. ( 1.2 ) Efficacy was established in two 6-week clinical trials in adults ( 14.2 ). Maintenance efficacy has not been systematically evaluated. As Olanzapine and Fluoxetine in Combination for the: Treatment of depressive episodes associated with bipolar I disorder.( 1.5 ) Efficacy was established with Symbyax (olanzapine and fluoxetine in combination); refer to the product label for Symbyax. Treatment of treatment resistant depression. (1.6) Efficacy was established with Symbyax (olanzapine and fluoxetine in combination) in adults; refer to the product label for Symbyax. 1.1 Schizophrenia Oral olanzapine is indicated for the treatment of schizophrenia. Efficacy was established in three clinical trials in adult patients with schizophrenia: two 6-week trials and one maintenance trial. In adolescent patients with schizophrenia (ages 13 to 17), efficacy was established in one 6-week trial [ see Clinical Studies ( 14.1 )]. When deciding among the alternative treatments available for adolescents, clinicians should consider the increased potential (in adolescents as compared with adults) for weight gain and dyslipidemia. Clinicians should consider the potential long-term risks when prescribing to adolescents, and in many cases this may lead them to consider prescribing other drugs first in adolescents [see Warnings and Precautions ( 5.5 ) ]. 1.2 Bipolar I Disorder (Manic or Mixed Episodes) Monotherapy Oral olanzapine is indicated for the acute treatment of manic or mixed episodes associated with bipolar I disorder and maintenance treatment of bipolar I disorder. Efficacy was established in three clinical trials in adult patients with manic or mixed episodes of bipolar I disorder: two 3- to 4-week trials and one monotherapy maintenance trial. In adolescent patients with manic or mixed episodes associated with bipolar I disorder (ages 13 to 17), efficacy was established in one 3-week trial [see Clinical Studies ( 14.2 ) ]. When deciding among the alternative treatments available for adolescents, clinicians should consider the increased potential (in adolescents as compared with adults) for weight gain and dyslipidemia. Clinicians should consider the potential long-term risks when prescribing to adolescents, and in many cases this may lead them to consider prescribing other drugs first in adolescents [see Warnings and Precautions ( 5.5 ) ]. …

Olanzapine Tablets USP, 15 mg are white, film coated, round, biconvex tablets with “R” 15 debossed on one side and “0167” on other side. Olanzapine Tablets USP, 20 mg are white, film coated, oval, biconvex tablets with “R” 20 debossed on one side and “0168” on other side. Tablets (not scored): 15, 20 mg ( 3 )

16.1 How Supplied Olanzapine Tablets USP, 15 mg are white, film coated, round, biconvex tablets with “R” debossed 15 on one side and “0167” on other side and are supplied in bottles of 30, 100, 500 and unit-dose packages of 100 (10 x 10). Bottles of 30 NDC 55111-167-30 Bottles of 100 NDC 55111-167-01 Bottles of 500 NDC 55111-167-05 Unit dose packages of 100 (10 x10) NDC 55111-167-78 Olanzapine Tablets USP, 20 mg are white, film coated, oval, biconvex tablets with “R” debossed on 20 one side and “0168” on other side and are supplied in bottles of 30, 60, 100, 500 and unit-dose packages of 100 (10 x 10). Bottles of 30 NDC 55111-168-30 Bottles of 60 NDC 55111-168-60 Bottles of 100 NDC 55111-168-01 Bottles of 500 NDC 55111-168-05 Unit dose packages of 100 (10 x10) NDC 55111-168-78 16.2 Storage and Handling Store olanzapine tablets at controlled room temperature, 20° to 25°C (68° to 77°F) [see USP]. The USP defines controlled room temperature as a temperature maintained thermostatically that encompasses the usual and customary working environment of 20° to 25°C (68° to 77°F); that results in a mean kinetic temperature calculated to be not more than 25°C; and that allows for excursions between 15° and 30°C (59° and 86°F) that are experienced in pharmacies, hospitals, and warehouses. Protect olanzapine tablets from light and moisture.

None with olanzapine monotherapy. When using olanzapine and fluoxetine in combination, also refer to the Contraindications section of the package insert for Symbyax. For specific information about the contraindications of lithium or valproate, refer to the Contraindications section of the package inserts for these other products. None with olanzapine monotherapy. (4) When using olanzapine and fluoxetine in combination, also refer to the Contraindications section of the package insert for Symbyax®. (4) When using olanzapine in combination with lithium or valproate, refer to the Contraindications section of the package inserts for those products ( 4 )

When using olanzapine and fluoxetine in combination, also refer to the Warnings and Precautions section of the package insert for Symbyax. 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 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 a history of seizures or with conditions that potentially lower the seizure threshold (5.11) Potential for Cognitive and Motor Impairment: Has potential to impair judgment, thinking, and motor skills. Use caution when operating machinery (5.12) Anticholinergic (antimuscarinic) Effects: Use with caution with other anticholinergic drugs and in patients with urinary retention, prostatic hypertrophy, constipation, paralytic ileus or related conditions. ( 5.14 ) Hyperprolactinemia: May elevate prolactin levels (5.15) Use in Combination with Fluoxetine, Lithium or Valproate: Also refer to the package inserts for Symbyax, lithium, or valproate (5.16) Laboratory Tests: Monitor fasting blood glucose and lipid profiles at the beginning of, and periodically during, treatment. (5.17) 5.1 Elderly Patients with Dementia-Related Psychosis Increased Mortality Elderly patients with dementiarelated 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. [see Boxed Warning, Use in Specific Populations (8.5), and Patient Counseling Information (17)]. In placebo-controlled clinical trials of elderly patients with dementia-related psychosis, the incidence of death in olanzapine-treated patients was significantly greater than placebo-treated patients (3.5% vs 1.5%, respectively). Cerebrovascular Adverse Events (CVAE), Including Stroke Cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, were reported in patients in trials of olanzapine in elderly patients with dementia-related psychosis. In placebo-controlled trials, there was a significantly higher incidence of cerebrovascular adverse events in patients treated with olanzapine compared to patients treated with placebo. Olanzapine is not approved for the treatment of patients with dementia-related psychosis [see Boxed Warning and Patient Counseling Information (17) ]. 5.2 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. Prescriptions for olanzapine should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose. 5.3 Neuroleptic Malignant Syndrome (NMS) A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs, including olanzapine. 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 creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to exclude cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). …

When using olanzapine and fluoxetine in combination, also refer to the Adverse Reactions section of the package insert for Symbyax. 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. …

The risks of using olanzapine in combination with other drugs have not been extensively evaluated in systematic studies. Diazepam: May potentiate orthostatic hypotension ( 7.1, 7.2 ) Alcohol: May potentiate orthostatic hypotension ( 7.1 ) Carbamazepine: Increased clearance of olanzapine ( 7.1) Fluvoxamine: May increase olanzapine levels ( 7.1 ) Olanzapine and Fluoxetine in Combination: Also refer to the DrugInteractions section of the package insert for Symbyax. …