Olanzapine
HIGHLIGHTS OF PRESCRIBING INFORMATIONHIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use olanzapine tablets USP safely and effectively. See full prescribing information for olanzapine tablets USP. OLANZAPINE tablets USP for oral use. Initial U.S. Approval: 1996 BOXED WARNINGWARNING: 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. INDICATIONS AND USAGE INDICATIONS AND USAGE Olanzapine USP 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) 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) 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 olanzapine and fluoxetine in combination in adults; refer to the product label for olanzapine and fluoxetine in combination. DOSAGE AND ADMINISTRATION DOSAGE AND ADMINISTRATION Schizophrenia in adults (2.1) Oral: Start at 5 to 10 mg once daily; Target 10 mg/day within several days Bipolar I Disorder (manic or mixed episodes) in adults (2.2) Oral: Start at 10 or 15 mg once daily Bipolar I Disorder (manic or mixed episodes) with lithium or valproate in adults (2.2) Oral: Start at 10 mg once daily Depressive Episodes associated with Bipolar I Disorder in adults (2.5) Oral in combination with fluoxetine: Start at 5 mg or oral olanzapine and 20 mg of fluoxetine once daily Lower starting dose recommended in debilitated or pharmacodynamically sensitive patients or patients with predisposition to hypotensive reactions, or with potential for slowed metabolism (2.1) Olanzapine may be given without regard to meals (2.1) Olanzapine and Fluoxetine in Combination: Dosage adjustments, if indicated, should be made with the individual components according to efficacy and tolerability. (2.5) Olanzapine monotherapy is not indicated for the treatment of depressive episodes associated with bipolar I disorder. (2.5) Safety of coadministration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated. (2.5) DOSAGE FORMS AND STRENGTHS DOSAGE FORMS AND STRENGTHS Tablets (not scored): 2.5, 5, 7.5, 10, 15 mg (3) CONTRAINDICATIONS CONTRAINDICATIONS None with olanzapine monotherapy When using olanzapine and fluoxetine in combination, also refer to the Contraindications section of the package insert for olanzapine and fluoxetine in combination. When using olanzapine in combination with lithium or valproate, refer to the Contraindications section of the package inserts for those products (4) 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) Side Effects 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)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/medwatchDRUG INTERACTIONS Diazepam: May potentiate or orthostatic hypotension (7.1, 7.2) Alcohol: May potentiate orthostatic hypotension (7.1) Carboamazepine: Increased clearance of olanzapine (7.1) Fluvoxamine: May increase olanzapine levels (7.1) Olanzapine and Fluoxetine in Combination: Also refer to the Drug Interactions section of the package insert of olanzapine and fluoxetine in combination (7.1) CNS Acting Drugs: Caution should be used with taken in combination with other centrally acting drugs and alcohol (7.2) Antihypertensive Agents: Enhanced antihypertensive effect (7.2) Levodopa and Dopamine Agonists: May antagonize levodopa/dopamine agonists (7.2) Other Concomittant Drug Therapy: When using olanzapine in combination with lithium or valporate, refer to the Drug Interactions sections of the package insert for those products (7.2.) USE IN SPECIFIC POPULATIONSEnter highlights text here
FULL PRESCRIBING INFORMATION: CONTENTS*
- FULL PRESCRIBING INFORMATION
- WARNING
- INDICATIONS & USAGE
- DOSAGE & ADMINISTRATION
- DOSAGE FORMS & STRENGTHS
- OLANZAPINE CONTRAINDICATIONS
- WARNINGS AND PRECAUTIONS
- OLANZAPINE ADVERSE REACTIONS
- DRUG INTERACTIONS
- USE IN SPECIFIC POPULATIONS
- DRUG ABUSE AND DEPENDENCE
- OVERDOSAGE
- OLANZAPINE DESCRIPTION
- CLINICAL PHARMACOLOGY
- NONCLINICAL TOXICOLOGY
- CLINICAL STUDIES
- HOW SUPPLIED
- STORAGE AND HANDLING
- PATIENT COUNSELING INFORMATION
- Medication Guide
- PACKAGE LABEL.PRINCIPAL DISPLAY PANEL SECTION
FULL PRESCRIBING INFORMATION
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE1.1 Schizophrenia
1.2 Bipolar I Disorder (Manic or Mixed Episodes)
1.3 Special Considerations in Treating Pediatric Schizophrenia and Bipolar I Disorder
1.5 Olanzapine and Fluoxetine in Combination: Depressive Episodes Associated with Bipolar I Disorder
2 DOSAGE AND ADMINISTRATION
2.1 Schizophrenia
2.2 Bipolar I Disorder (Manic or Mixed Episodes)
2.5 Olanzapine and Fluoxetine in Combination: Depressive Episodes Associated with Bipolar I Disorder
2.7 Olanzapine and Fluoxetine in Combination: Dosing in Special Populations
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Elderly Patients with Dementia-Related Psychosis
5.2 Suicide
5.3 Neuroleptic Malignant Syndrome (NMS)
5.4 Hyperglycemia
5.5 Hyperlipidemia
5.6 Weight Gain
5.7 Tardive Dyskinesia
5.8 Orthostatic Hypotension
5.9 Leukopenia, Neutropenia, and Agranulocytosis
5.10 Dysphagia
5.11 Seizures
5.12 Potential for Cognitive and Motor Impairment
5.13 Body Temperature Regulation
5.14 Use in Patients with Concomitant Illness
5.15 Hyperprolactinemia
5.16 Use in Combination with Fluoxetine, Lithium or Valproate
5.17 Laboratory Tests
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Vital Signs and Laboratory Studies
6.3 Postmarketing Experience
7 DRUG INTERACTIONS
7.1 Potential for Other Drugs to Affect Olanzapine
7.2 Potential for Olanzapine to Affect Other Drugs
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Labor and Delivery
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
9 DRUG ABUSE AND DEPENDENCE
9.3 Dependence
10 OVERDOSAGE
10.1 Human Experience
10.2 Management of Overdose
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
13.2 Animal Toxicology and/or Pharmacology
14 CLINICAL STUDIES
14.1 Schizophrenia
14.2 Bipolar I Disorder (Manic or Mixed Episodes)
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
16.2 Storage and Handling
17 PATIENT COUNSELING INFORMATION
17.1 Information on Medication Guide
17.2 Elderly Patients with Dementia-Related Psychosis: Increased Mortality and Cerebrovascular Adverse Events (CVAE), Including Stroke
17.3 Neuroleptic Malignant Syndrome (NMS)
17.4 Hyperglycemia
17.5 Hyperlipidemia
17.6 Weight Gain
17.7 Orthostatic Hypotension
17.8 Potential for Cognitive and Motor Impairment
17.9 Body Temperature Regulation
17.10 Concomitant Medication
17.11 Alcohol
17.13 Use in Specific Populations
17.14 Need for Comprehensive Treatment Program in Pediatric Patients
Medication guide
PRINCIPAL DISPLAY PANEL
Olanzapine Tablets USP 2.5mg 30s Label Text
PRINCIPAL DISPLAY PANEL
Olanzapine Tablets USP 5mg 30s Label Text
PRINCIPAL DISPLAY PANEL
Olanzapine Tablets USP 7.5mg 30s Label Text
PRINCIPAL DISPLAY PANEL
Olanzapine Tablets USP 10mg 30s Label Text
PRINCIPAL DISPLAY PANEL
Olanzapine Tablets USP 15mg 30s Label Text
WARNING
INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSISElderly 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.
INDICATIONS & USAGE
1.1 Schizophrenia14.1)].
5.5,5.6)].
1.2 Bipolar I Disorder (Manic or Mixed Episodes)
Monotherapy
14.2)].
5.5,5.6)].
Adjunctive Therapy to Lithium or Valproate
14.2)].
1.3 Special Considerations in Treating Pediatric Schizophrenia and Bipolar I Disorder
1.5 Olanzapine and Fluoxetine in Combination: Depressive Episodes Associated with Bipolar I Disorder
DOSAGE & ADMINISTRATION
2.1 SchizophreniaAdults
5.14), Drug Interactions (7), and Clinical Pharmacology (12.3)]. When indicated, dose escalation should be performed with caution in these patients.
14.1)]. The physician who elects to use olanzapine for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.
Adolescents
2.2 Bipolar I Disorder (Manic or Mixed Episodes)
Adults
14.2)].
14.2)]. The physician who elects to use olanzapine for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.
14.2)]. The safety of doses above 20 mg/day has not been evaluated in clinical trials.
Adolescents
2.5 Olanzapine and Fluoxetine in Combination: Depressive Episodes Associated with Bipolar I Disorder
Table 1: Approximate Dose Correspondence Between Olanzapine and Fluoxetine in Combination and the Combination of Olanzapine and Fluoxetine
For Use in Combination olanzapine and fluoxetine in combination
(mg/day) Olanzapine
(mg/day) Fluoxetine
(mg/day)
2.7 Olanzapine and Fluoxetine in Combination: Dosing in Special Populations
5.14), Drug Interactions (7), and Clinical Pharmacology (12.3)].
DOSAGE FORMS & STRENGTHS
OLANZAPINE CONTRAINDICATIONS
WARNINGS AND PRECAUTIONS
5.1 Elderly Patients with Dementia-Related Psychosis
Increased Mortality
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 [see Boxed Warning, Warnings and Precautions ( 5.14), and Patient Counseling Information ( 17.2)].
17.2)].
5.2 Suicide
5.3 Neuroleptic Malignant Syndrome (NMS)
17.3)].
5.4 Hyperglycemia
17.4)].
Olanzapine Monotherapy in Adults
Table 2 shows short-term and long-term changes in fasting glucose levels from adult olanzapine monotherapy studies.
Table 2: Changes in Fasting Glucose Levels from Adult Olanzapine Monotherapy Studies
*
Up to 12 weeks exposure At least 48 weeks exposure Laboratory Analyte Category Change (at least once) from Baseline Treatment Arm N Patients N Patients
**
**
Olanzapine Monotherapy in Adolescents
Table 3 shows short-term and long-term changes in fasting blood glucose from adolescent olanzapine monotherapy studies.
Table 3: Changes in Fasting Glucose Levels from Adolescent Olanzapine Monotherapy Studies
Up to 12 weeks exposure At least 24 weeks exposure Laboratory Analyte Category Change (at least once) from Baseline Treatment Arm N Patients N Patients
5.5 Hyperlipidemia
17.5)].
Olanzapine Monotherapy in Adults
Table 4 shows categorical changes in fasting lipids values.
Table 4: Changes in Fasting Lipids Values from Adult Olanzapine Monotherapy Studies
*
Up to 12 weeks exposure At least 48 weeks exposure Laboratory Analyte Category Change (at least once) from Baseline Treatment Arm N Patients N Patients **
**
****
**
****
**
**
Olanzapine Monotherapy in Adolescents
Table 5 shows categorical changes in fasting lipids values in adolescents.
Table 5: Changes in Fasting Lipids Values from Adolescent Olanzapine Monotherapy Studies
Up to 6 weeks exposure At least 24 weeks exposure Laboratory Analyte Category Change (at least once) from Baseline Treatment Arm N Patients N Patients
5.6 Weight Gain
17.6)].
Olanzapine Monotherapy in Adults
Table 6 includes data on adult weight gain with olanzapine pooled from 86 clinical trials. The data in each column represent data for those patients who completed treatment periods of the durations specified.
Table 6: Weight Gain with Olanzapine Use in Adults
Amount Gained kg (lb) 6 Weeks
(N = 7465)
(%) 6 Months
(N = 4162)
(%) 12 Months
(N = 1345)
(%) 24 Months
(N = 474)
(%) 36 Months
(N = 147)
(%)
Olanzapine Monotherapy in Adolescents
Table 7: Weight Gain with Olanzapine Use in Adolescents from 4 Placebo-Controlled Trials
Olanzapine-treated patients Placebo-treated patients
Table 8 shows data on adolescent weight gain with olanzapine pooled from 6 clinical trials. The data in each column represent data for those patients who completed treatment periods of the durations specified. Little clinical trial data is available on weight gain in adolescents with olanzapine beyond 6 months of treatment.
Table 8: Weight Gain with Olanzapine Use in Adolescents
Amount Gained kg (lb) 6 Weeks (N = 243) (%) 6 Months (N = 191) (%)
5.7 Tardive Dyskinesia
5.8 Orthostatic Hypotension
17.7)].
2)]. A more gradual titration to the target dose should be considered if hypotension occurs.
7)].
5.9 Leukopenia, Neutropenia, and Agranulocytosis
Class Effect
5.10 Dysphagia
5.11 Seizures
5.12 Potential for Cognitive and Motor Impairment
17.8)].
5.13 Body Temperature Regulation
17.9)].
5.14 Use in Patients with Concomitant Illness
12.3)].
5.1), and Patient Counseling Information (17.2)].
5.8)].
5.15 Hyperprolactinemia
13.1
8.4)].
5.16 Use in Combination with Fluoxetine, Lithium or Valproate
7)].
5.17 Laboratory Tests
5.4,5.5) and Patient Counseling Information (17.4,17.5)].
OLANZAPINE ADVERSE REACTIONS
6.1 Clinical Trials Experience
Clinical Trials in Adults
Adverse Reactions Associated with Discontinuation of Treatment in Short-Term, Placebo-Controlled Trials
Bipolar I Disorder(Manic or Mixed Episodes), Olanzapine in Combination with Lithium or Valproate
Table 9: Common Treatment-Emergent Adverse Reactions Associated with the use of Oral Olanzapine in 6 Week TrialsSCHIZOPHRENIA
*
Adverse Reaction Percentage of Patients Reporting Event Olanzapine (N = 248) Placebo (N = 118) *
Table 10: Common Treatment-Emergent Adverse Reactions Associated with the use of Oral Olanzapine in 3 Week and 4 Week TrialsBipolar I Disorder (Manic or Mixed Episodes)
Adverse Reaction Percentage of Patients Reporting Event Olanzapine (N = 125) Placebo (N = 129)
Table 11: Treatment-Emergent Adverse Reactions: Incidence in Short-Term, Placebo-Controlled Clinical Trials with Oral Olanzapine
Body System/Adverse Reaction Percentage of Patients Reporting Event Olanzapine (N = 532) Placebo (N = 294) Cardiovascular System Digestive System Hemic and Lymphatic System Metabolic and Nutritional Disorders Musculoskeletal System Nervous System Respiratory System Special Senses Urogenital System
Table 12: Common Treatment-Emergent Adverse Reactions Associated with the Use of Oral Olanzapine in 6 Week Combination Trials - Bipolar I Disorder (Manic or Mixed Episodes)
Adverse Reaction Percentage of Patients Reporting Event Olanzapine with lithium or valproate (N = 229) Placebo with lithium or valproate (N = 115)
Table 13: Treatment-Emergent Adverse Reactions: Incidence in Short-Term, Placebo-Controlled Clinical Trials of Oral Olanzapine in Combination with Lithium or Valproate
*
Percentage of Patients Reporting Event Body System/Adverse Reaction Olanzapine with lithium or valproate (N = 229) Placebo with lithium or valproate (N = 115) Body as a Whole Cardiovascular System Digestive System Metabolic and Nutritional Disorders Nervous System Respiratory System Skin and Appendages Special Senses Urogenital System *
Additional Findings Observed in Clinical Trials
Extrapyramidal Symptoms
Table 15: Treatment-Emergent Extrapyramidal Symptoms Assessed by Rating Scales Incidence in a Fixed Dosage Range, Placebo-Controlled Clinical Trial of Oral Olanzapine in Schizophrenia - Acute Phase
**
Percentage of Patients Reporting Event Placebo Olanzapine 52.5 mg/day Olanzapine 102.5 mg/day Olanzapine 152.5 mg/day
Table 16: Treatment-Emergent Extrapyramidal Symptoms Assessed by Adverse Reactions Incidence in a Fixed Dosage Range, Placebo-Controlled Clinical Trial of Oral Olanzapine in Schizophrenia - Acute Phase
*
Percentage of Patients Reporting Event Placebo (N = 68) Olanzapine 52.5 mg/day (N = 65) Olanzapine 102.5 mg/day (N = 64) Olanzapine 152.5 mg/day (N = 69) *
Table 17: Treatment-Emergent Extrapyramidal Symptoms Assessed by Adverse Reactions Incidence in Placebo-Controlled Clinical Trials of Oral Olanzapine in Schizophrenia and Bipolar I DisorderAdolescents
Percentage of Patients Reporting Event Categoriesa Placebo (N = 89) Olanzapine (N = 179)
Dystonia, Class Effect
Other Adverse Reactions
Table 20: Percentage of Patients from a Schizophrenia Trial with Treatment-Emergent Adverse Reactions for the Three Dose Range Groups and Placebo
Percentage of Patients Reporting Event Adverse Event Placebo (N = 68) Olanzapine 52.5 mg/day (N = 65) Olanzapine 102.5 mg/day (N = 64) Olanzapine 152.5 mg/day (N = 69)
Differences among Fixed-Dose Groups Observed in Other Olanzapine Clinical Trials
Other Adverse Reactions Observed During the Clinical Trial Evaluation of Oral Olanzapine
Body as a Whole- Infrequent: chills, face edema, photosensitivity reaction, suicide attempt: Rare: chills and fever, hangover effect, sudden death.
Cardiovascular System-Infrequent: cerebrovascular accident, vasodilatation.
Digestive System- Infrequent: nausea and vomiting, tongue edema, Rare: ileus, intestinal obstruction, liver fatty deposit.
Hemic and Lymphatic System-Infrequent: leukopenia, thrombocytopenia.
Metabolic and Nutritional Disorders-Infrequent: alkaline phosphatase increased, bilirubinemia, hypoproteinemia.
Musculoskeletal System-Rare: osteoporosis.
Nervous System-infreequent: ataxia, dysarthria, libido decreased, stupor; Rare: coma.
Respiratory System- Infrequent: epistaxis; Rare: lung edema.
Skin and Appendages-Infrequent: alopecia.
Special Senses- Infrequent: abnormality of accommodation, dry eyes; Rare: mydriasis.
Urogenital System-Infrequent: amenorrhea2, breast pain, decreased menstruation, impotence2, increased menstruation2, menorrhagia2, metrorrhagia2, polyuria2, urinary frequency, urinary retention, urinary urgency, urination impaired.
Clinical Trials in Adolescent Patients (age 13 to 17 years)
Table 21.
Table 21: Treatment-Emergent Adverse Reactions ofIncidence among Adolescents (13 to 17 Years Old) with Schizophrenia or Bipolar I Disorder (Manic or Mixed Episodes)
Adverse Reactions Percentage of Patients Reporting Event 6 Week Trial % Schizophrenia Patients 3 Week Trial % Bipolar Patients Olanzapine (N = 72) Placebo
(N = 35) Olanzapine (N = 107) Placebo
(N = 54)
Table 22.
Table 22: Treatment-Emergent Adverse Reactions of2% Incidence among Adolescents (13 to 17 Years Old)
(Combined Incidence from Short-Term, Placebo-Controlled Clinical Trials of Schizophreniaor Bipolar I Disorder [Manic or Mixed Episodes])
Percentage of Patients Reporting Event
Olanzapine Placebo Adverse Reaction (N = 179) (N = 89)
6.2 Vital Signs and Laboratory Studies
Vital Sign Changes
5)].
Laboratory Changes
5.15)], with an asymptomatic elevation of the eosinophil count in 0.3% of patients, and with an increase in CPK.
ECG Changes
5.8)].
6.3 Postmarketing Experience
DRUG INTERACTIONS
7.1 Potential for Other Drugs to Affect Olanzapine
Diazepam
7.2)].
Cimetidine and Antacids
Inducers of CYP1A2
Alcohol
7.2)].
Inhibitors of CYP1A2
Inhibitors of CYP2D6
Warfarin
7.2)].
Inducers of CYP1A2 or Glucuronyl Transferase
Charcoal
7.2 Potential for Olanzapine to Affect Other Drugs
CNS Acting Drugs
Antihypertensive Agents
Levodopa and Dopamine Agonists
Lithium
5.16)].
Valproate
5.16)].
Effect of Olanzapine on Drug Metabolizing Enzymes
Imipramine
Warfarin
7.1)].
Diazepam
7.1)].
Alcohol
7.1)].
Biperiden
Theophylline
USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Teratogenic Effects
Non-Teratogenic Effects
8.2 Labor and Delivery
8.3 Nursing Mothers
8.4 Pediatric Use
5.5,5.6,5.15,5.17) and Adverse Reactions (6.2)]. 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 hyperlipidemia.
17.13)].
8.5 Geriatric Use
2.1), and Warnings and Precautions (5.1)].
DRUG ABUSE AND DEPENDENCE
9.3 DependenceOVERDOSAGE
10.1 Human Experience10.2 Management of Overdose
OLANZAPINE DESCRIPTION
CLINICAL PHARMACOLOGY
12.1 Mechanism of Action12.2 Pharmacodynamics
12.3 Pharmacokinetics
Oral Administration, Monotherapy
12.3)].
Metabolism and Elimination
Specific Populations
2)].
2)].
NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of FertilityCarcinogenesis
5.15)].
Mutagenesis
Impairment of Fertility
13.2 Animal Toxicology and/or Pharmacology
CLINICAL STUDIES
14.1 Schizophrenia
Adults
Adolescents
14.2 Bipolar I Disorder (Manic or Mixed Episodes)
Adults
Adolescents
HOW SUPPLIED
STORAGE AND HANDLING
PATIENT COUNSELING INFORMATION
17.1 Information on Medication Guide
17.2 Elderly Patients with Dementia-Related Psychosis: Increased Mortality and Cerebrovascular Adverse Events (CVAE), Including Stroke
5.1)].
17.3 Neuroleptic Malignant Syndrome (NMS)
5.3)].
17.4 Hyperglycemia
5.4)].
17.5 Hyperlipidemia
5.5)].
17.6 Weight Gain
5.6)].
17.7 Orthostatic Hypotension
5.8) and Drug Interactions (7)]. Patients should be advised to change positions carefully to help prevent orthostatic hypotension, and to lie down if they feel dizzy or faint, until they feel better. Patients should be advised to call their doctor if they experience any of the following signs and symptoms associated with orthostatic hypotension: dizziness, fast or slow heart beat, or fainting.
17.8 Potential for Cognitive and Motor Impairment
5.12)].
17.9 Body Temperature Regulation
5.13)].
17.10 Concomitant Medication
7)].
17.11 Alcohol
7)].
17.13 Use in Specific Populations
Pregnancy
8.1)].
Nursing Mothers
8.3)].
Pediatric Use
5.5,5.6) and Use in Specific Populations (8.4)].
17.14 Need for Comprehensive Treatment Program in Pediatric Patients
Medication Guide
What is the most important information I should know about olanzapine?
Olanzapine may cause serious side effects, including:
1. Increased risk of death in elderly people who are confused, have memory loss and have lost touch with reality (dementia-related psychosis).
2. High blood sugar (hyperglycemia).
3. High fat levels in your blood (increased cholesterol and triglycerides), especially in teenagers age 13 to 17.
4. Weight gain, especially in teenagers age 13 to 17.
These serious side effects are described below.
1. Increased risk of death in elderly people who are confused, have memory loss and have lost touch with reality (dementia-related psychosis).Olanzapine is not approved for treating psychosis in elderly people with dementia.
2. High blood sugar (hyperglycemia).High blood sugar can happen if you have diabetes already or if you have never had diabetes. High blood sugar could lead to:
Call your doctorif you have any of these symptoms of high blood sugar (hyperglycemia) while taking olanzapine:
3. High fat levels in your blood (cholesterol and triglycerides).High fat levels may happen in people treated with olanzapine, especially in teenagers (13 to 17 years old). You may not have any symptoms, so your doctor should do blood tests to check your cholesterol and triglyceride levels before you start taking olanzapine and during treatment.
4. Weight gain.Weight gain is very common in people who take olanzapine. Teenagers (13 to 17 years old) are more likely to gain weight and to gain more weight than adults. Some people may gain a lot of weight while taking olanzapine, so you and your doctor should check your weight regularly. Talk to your doctor about ways to control weight gain, such as eating a healthy, balanced diet, and exercising.
What is olanzapine?
Olanzapine is a prescription medicine used to treat:
What should I tell my doctor before taking olanzapine?
thoughts of suicideor of hurting yourself or others. If you have these thoughts at any time, tell your doctor or go to an emergency room right away.
How should I take olanzapine?
To prevent serious side effects, do not stop taking olanzapine suddenly. If you need to stop taking olanzapine, your doctor can tell you how to safely stop taking it.
If you take too much olanzapine, call your doctor or poison control center right away at 1-800-222-1222, or get emergency treatment.
What should I avoid while taking olanzapine?
What are the possible side effects of olanzapine?
Serious side effects may happen when you take olanzapine, including:
Seeis the most important information I should know about olanzapine?which describes the increased risk of death in elderly people with dementia-related psychosis and the risks of high blood sugar, high cholesterol and triglyceride levels, and weight gain.
Increased incidence of stroke orcalled transient ischemic attacks (TIAs) in elderly people with dementia-related psychosis(elderly people who have lost touch with reality due to confusion and memory loss). Olanzapine is not approved for these patients.
Neuroleptic Malignant Syndrome (NMS):NMS is a rare but very serious condition that can happen in people who take antipsychotic medicines, including olanzapine. NMS can cause death and must be treated in a hospital. Call your doctor right away if you become severely ill and have any of these symptoms:
Tardive Dyskinesia:This condition causes body movements that keep happening and that you cannot control. These movements usually affect the face and tongue. Tardive dyskinesia may not go away, even if you stop taking olanzapine. It may also start after you stop taking olanzapine. Tell your doctor if you get any body movements that you cannot control.
Decreased blood pressure when you change positions, with symptoms of dizziness, fast or slow heart beat, or fainting.
Difficulty swallowing, that can cause food or liquid to get into your lungs.
Seizures: Tell your doctor if you have a seizure during treatment with olanzapine.
Problems with control of body temperature:You could become very hot, for instance when you exercise a lot or stay in an area that is very hot. It is important for you to drink water to avoid dehydration. Call your doctor right away if you become severely ill and have some or all of these symptoms of dehydration:
Common possible side effects of olanzapine include:lack of energy, dry mouth, increased appetite, sleepiness, tremor (shakes), having hard or infrequent stools, dizziness, changes in behavior, or restlessness.
Other common side effects in teenagers (13 to 17 years old) include:headache, stomach-area (abdominal) pain, pain in your arms or legs, or tiredness. Teenagers experienced greater increases in prolactin, liver enzymes, and sleepiness, as compared with adults.
How should I store olanzapine?
Keep olanzapine and all medicines out of the reach of children.
What are the ingredients in olanzapine tablets USP?
Active ingredient:olanzapine USP
Inactive ingredients:anhydrous lactose, carrageenan, crospovidone, magnesium stearate, microcrystalline cellulose, and polyethylene glycol. In addition, the 2.5 mg, 5 mg, 7.5 mg and 10 mg tablets contain titanium dioxide, and the 15 mg tablets contain FD&C blue #2 aluminum lake.
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL SECTION
OlanzapineOLANZAPINE TABLET, FILM COATED
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
PLEASE, BE CAREFUL!
Be sure to consult your doctor before taking any medication!
