Olanzapine is an active pharmaceutical ingredient in the Diazepines, Oxazepines, Thiazepines and Oxepines group (N05AH). The information below is compiled per regulator from the product labels on record, with direct links to the original documents.
GBOfficial regulatory label· revised August 30, 2024[1]
Adults Olanzapine is indicated for the treatment of schizophrenia. Olanzapine is effective in maintaining the clinical improvement during continuation therapy in patients who have shown an initial treatment response. Olanzapine is indicated for the treatment of moderate to severe manic episode.
1).
How to take
CACanada· Health Canada
124 products
Uses
CAOfficial regulatory label· revised March 24, 2026[2]
ZYPREXA (oral olanzapine) is indicated for • the acute treatment of schizophrenia and related psychotic disorders • maintenance treatment of schizophrenia and related psychotic disorders. In controlled clinical trials, ZYPREXA was found to improve both positive and negative symptoms.
ZYPREXA has been shown to be effective in maintaining clinical improvement during 1-year of continuation therapy in patients who had shown an initial treatment response. ZYPREXA (oral olanzapine) is indicated for the acute treatment of • manic or mixed episodes in bipolar I disorder.
, lithium or divalproex sodium). The efficacy of ZYPREXA as monotherapy maintenance treatment in bipolar patients with manic or mixed episodes who responded to acute treatment with ZYPREXA was demonstrated in two 1-year “time to relapse” trials (see 14 CLINICAL TRIALS).
The physician who elects to use ZYPREXA for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient (see 4 DOSAGE AND ADMINISTRATION section). ZYPREXA IntraMuscular (intramuscular olanzapine) is indicated for • the rapid control of agitation in patients with schizophrenia and • related psychotic disorders, and • bipolar mania.
USUnited States· FDA
10 products
Uses
USOfficial regulatory label· revised July 10, 2023[3]
1 INDICATIONS AND USAGE Olanzapine is an atypical antipsychotic indicated: As oral formulation for the: Treatment of schizophrenia. 1 ) Adults: Efficacy was established in three clinical trials in patients with schizophrenia: two 6-week trials and one maintenance trial.
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 ) Acute treatment of manic or mixed episodes associated with bipolar I disorder and maintenance treatment of bipolar I disorder.
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. 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.
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. 3 ) Adjunct to valproate or lithium in the treatment of manic or mixed episodes associated with bipolar I disorder.
EUEuropean Union· EMA
10 products
Uses
EUOfficial regulatory label· revised May 12, 2026[4]
Adults Olanzapine is indicated for the treatment of schizophrenia. Olanzapine is effective in maintaining the clinical improvement during continuation therapy in patients who have shown an initial treatment response. Olanzapine is indicated for the treatment of moderate to severe manic episode.
1).
How to take
Drug interactions
Known interactions involving Olanzapine. Select one for details. This list is informational and not a complete interaction checker.
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[1]MHRA (UK) · PL317500018 · revised August 30, 2024
[2]Health Canada (DPD) · 02229250 · revised March 24, 2026
[3]FDA DailyMed · 002dd00f-7946-ea… · revised July 10, 2023 [PDF]
[4]European Medicines Agency · EMEA/H/C/001088 · revised May 12, 2026
[5]OpenFDA adverse-event reports (US), 12 months ending June 4, 2026.
Information on this page is compiled from public regulatory records. Drugvu is not affiliated with any regulator or pharmaceutical manufacturer. This is not medical advice. Always consult a qualified healthcare professional.
The recommended starting dose for olanzapine is 10 mg/day. 1).
Preventing recurrence in bipolar disorder:
The recommended starting dose is 10 mg/day. For patients who have been receiving olanzapine for treatment of manic episode, continue therapy for preventing recurrence at the same dose. If a new manic, mixed, or depressive episode occurs, olanzapine treatment should be continued (with dose optimisation as needed), with supplementary therapy to treat mood symptoms, as clinically indicated.
During treatment for schizophrenia, manic episode and recurrence prevention in bipolar disorder, daily dosage may subsequently be adjusted on the basis of individual clinical status within the range 5-20 mg/day. An increase to a dose greater than the recommended starting dose is advised only after appropriate clinical reassessment and should generally occur at intervals of not less than 24 hours.
Olanzapine can be given without regards for meals as absorption is not affected by food. Gradual tapering of the dose should be considered when discontinuing olanzapine. 4). Renal and/or hepatic impairment A lower starting dose (5 mg) should be considered for such patients.
In cases of moderate hepatic insufficiency (cirrhosis, Child-Pugh Class A or B), the starting dose should be 5 mg and only increased with caution. Smokers The starting dose and dose range need not be routinely altered for non-smokers relative to smokers.
The metabolism of olanzapine may be induced by smoking. 5). When more than one factor is present which might result in slower metabolism (female gender, geriatric age, non-smoking status), consideration should be given to decreasing the starting dose.
Dose escalation, when indicated, should be conservative in such patients. ) Paediatric population Olanzapine is not recommended for use in children and adolescents below 18 years of age due to a lack of data on safety and efficacy. 2).
Method of administration For oral use.
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
GBOfficial regulatory label· Adverse reactions· revised August 30, 2024[1]
4), rash, asthenia, fatigue, pyrexia, arthralgia, increased alkaline phosphatase, high gamma glutamyltransferase, high uric acid, high creatine phosphokinase and oedema. Tabulated list of adverse reactions The following table lists the adverse reactions and laboratory investigations observed from spontaneous reporting and in clinical trials.
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
The frequency terms listed are defined as follows:
Very common ((≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the data available). 6) Reproductive system and breast disorders Erectile dysfunction in males Decreased libido in males and females Amenorrhea Breast enlargement Galactorrhea in females Gynaecomastia/breast enlargement in males Priapism12 General disorders and administration site conditions Asthenia Fatigue Oedema Pyrexia10 Investigations Elevated plasma prolactin levels8 Increased alkaline phosphatase10 High creatine phosphokinase11 High Gamma Glutamyltransferase10 High Uric Acid10 Increased total bilirubin 1 Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) categories.
8 %). 3 % respectively). 2 Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were greater in patients without evidence of lipid dysregulation at baseline. 2 mmol/l). 2 mmol/l) were very common.
56 mmol/l) which increased to high (≥ 7 mmol/l). 56 - < 7 mmol/l) to high (≥ 7 mmol/l) were very common. 26 mmol/l). 26 mmol/l) were very common. 6 In clinical trials, the incidence of Parkinsonism and dystonia in olanzapine-treated patients was numerically higher, but not statistically significantly different from placebo.
Olanzapine-treated patients had a lower incidence of Parkinsonism, akathisia and dystonia compared with titrated doses of haloperidol. In the absence of detailed information on the pre-existing history of individual acute and tardive extrapyramidal movement disorders, it cannot be concluded at present that olanzapine produces less tardive dyskinesia and/or other tardive extrapyramidal syndromes.
7 Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea and vomiting have been reported when olanzapine is stopped abruptly. 8 In clinical trials of up to 12 weeks, plasma prolactin concentrations exceeded the upper limit of normal range in approximately 30% […]
GBOfficial regulatory label· Warnings and precautions· revised August 30, 2024[1]
During antipsychotic treatment, improvement in the patient's clinical condition may take several days to some weeks. Patients should be closely monitored during this period. Dementia-related psychosis and/or behavioural disturbances Olanzapine is not recommended for use in patients with dementia-related psychosis and/or behavioural disturbances because of an increase in mortality and the risk of cerebrovascular accident.
5% vs. 5%, respectively). 4 mg) or duration of treatment. , pneumonia, with or without aspiration), or concomitant use of benzodiazepines. However, the incidence of death was higher in olanzapine-treated than in placebo-treated patients independent of these risk factors.
, stroke, transient ischemic attack), including fatalities, were reported. 3% vs. 4%, respectively). All olanzapine- and placebo-treated patients who experienced a cerebrovascular event had pre-existing risk factors. Age >75 years and vascular/mixed type dementia were identified as risk factors for CVAE in association with olanzapine treatment.
The efficacy of olanzapine was not established in these trials. Parkinson’s disease The use of olanzapine in the treatment of dopamine agonist associated psychosis in patients with Parkinson's disease is not recommended. 8), and olanzapine was not more effective than placebo in the treatment of psychotic symptoms.
In these trials, patients were initially required to be stable on the lowest effective dose of anti- Parkinsonian medicinal products (dopamine agonist) and to remain on the same anti-Parkinsonian medicinal products and dosages throughout the study.
5 mg/day and titrated to a maximum of 15 mg/day based on investigator judgement. Neuroleptic Malignant Syndrome (NMS) NMS is a potentially life-threatening condition associated with antipsychotic medicinal products. Rare cases reported as NMS have also been received in association with 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 creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
GBOfficial regulatory label· Contraindications· revised August 30, 2024[1]
1. Patients with known risk of narrow-angle glaucoma.
This is not medical advice. Consult a qualified healthcare professional.
The efficacy of ZYPREXA IntraMuscular for the control of agitation was established in 2 short-term (24 hours) placebo-controlled trials in agitated inpatients with schizophrenia and one short-term (24 hours) placebo- controlled trial in agitated patients with mania associated with bipolar disorder (see 14 CLINICAL TRIALS section).
1 Pediatrics Pediatrics: Based on the data submitted and reviewed by Health Canada, the safety and efficacy of Zyprexa in pediatric patients has not been established. 2 Geriatrics Geriatrics: Evidence from clinical studies and experience suggests that use in the geriatric population with dementia is associated with differences in safety or effectiveness.
4 Geriatrics). 2. CONTRAINDICATIONS ZYPREXA (olanzapine) is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the ZYPREXA Olanzapine / Olanzapine Tartrate Page 5 of 75 formulation, including any non-medicinal ingredient, or component of the container.
For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING section. 3. SERIOUS WARNINGS AND PRECAUTIONS BOX Serious Warnings and Precautions Increased Mortality in Elderly Patients with Dementia: Elderly patients with dementia treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo.
6-fold increase in death rate in the drug-treated patients. , pneumonia) in nature. (See 7 WARNINGS AND PRECAUTIONS, Special Populations, Use in Geriatric Patients with Dementia). 4. 1 Special Populations). Given the limited experience with ZYPREXA in the elderly, and the higher incidence of concomitant illness and concomitant medication in this population, ZYPREXA should be used with caution.
, nonsmoking female patients), or who may be pharmacodynamically more sensitive to ZYPREXA. When indicated, dose escalation should be performed with caution in these patients.
Patients with Hepatic and/or Renal Impairment:
As clinical experience is lacking in these patients, the lower initial starting dose and slower titration to initial target dose should be considered. 1 Special Populations). 5 mg) should be considered when clinical factors warrant. 2 Recommended Dose and Dosage Adjustment ORAL ADMINISTRATION Bioequivalence of the 15 mg and 20 mg tablets to multiple 5 mg tablets has been demonstrated.
These tablet formulations are equally well absorbed and can be readily interchanged. Pharmacokinetic studies showed that the ZYPREXA Tablets and ZYPREXA ZYDIS dosage forms are bioequivalent. ZYPREXA ZYDIS orally disintegrating tablets can be used as an alternative to ZYPREXA Tablets.
2 Study results ). ZYPREXA Olanzapine / Olanzapine Tartrate Page 6 of 75 Schizophrenia and Related Disorders Adults: ZYPREXA (olanzapine) should be administered on a once-a-day schedule without regard to meals, generally beginning with 5 to 10 mg, with a target dose of 10 mg/day within several days.
Further dosage adjustments, if indicated, should generally occur at intervals of not less than 1 week, since steady state for ZYPREXA would not be achieved for approximately 1 week in the typical patient. When dosage adjustments are necessary, dose increments/ decrements of 5 mg per day are recommended.
, to a dose of 15 mg/day or greater) is normally recommended only after clinical assessment. In clinical […]
How to take
CAOfficial regulatory label· revised March 24, 2026[2]
section). ZYPREXA IntraMuscular (intramuscular olanzapine) is indicated for • the rapid control of agitation in patients with schizophrenia and • related psychotic disorders, and • bipolar mania. The efficacy of ZYPREXA IntraMuscular for the control of agitation was established in 2 short-term (24 hours) placebo-controlled trials in agitated inpatients with schizophrenia and one short-term (24 hours) placebo- controlled trial in agitated patients with mania associated with bipolar disorder (see 14 CLINICAL TRIALS section).
1 Pediatrics Pediatrics: Based on the data submitted and reviewed by Health Canada, the safety and efficacy of Zyprexa in pediatric patients has not been established. 2 Geriatrics Geriatrics: Evidence from clinical studies and experience suggests that use in the geriatric population with dementia is associated with differences in safety or effectiveness.
4 Geriatrics). 2. CONTRAINDICATIONS ZYPREXA (olanzapine) is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the ZYPREXA Olanzapine / Olanzapine Tartrate Page 5 of 75 formulation, including any non-medicinal ingredient, or component of the container.
For a complete listing, see
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
CAOfficial regulatory label· Adverse reactions· revised March 24, 2026[2]
, Post-Market Adverse Drug Reactions).
Cardiac Death:
In a retrospective observational study, patients treated with atypical antipsychotics (including olanzapine) or typical antipsychotics had a similar dose-related increase of presumed sudden cardiac death (SCD) compared to ZYPREXA Olanzapine / Olanzapine Tartrate Page 12 of 75 non-users of antipsychotics (almost twice the risk than that for non-users).
In postmarketing reports with olanzapine, the event of SCD has been reported very rarely. Driving and Operating Machinery Potential Effect on Cognitive and Motor Performance: Because ZYPREXA may cause somnolence, patients should be cautioned about operating hazardous machinery, including motor vehicles, until they are reasonably certain that ZYPREXA therapy does not affect them adversely.
Exercise caution when driving or operating a vehicle or potentially dangerous machinery.
Endocrine and Metabolism Weight Gain:
Olanzapine was associated with weight gain during clinical trials. Clinically significant weight gain was observed across all baseline body mass index (BMI) categories (see 8 ADVERSE REACTIONS, Other Adverse Events Observed During Clinical Trials with Oral and Intramuscular Olanzapine Across All Indications, Weight Changes).
4 kg. The mean change in weight was comparable for patients with schizophrenia and bipolar mania. A retrospective analysis of 573 patients receiving olanzapine for up to 3 years found that dose was not a significant predictor of greater long-term changes in weight.
In long-term studies (at least 48 weeks), both the magnitude of weight gain and the proportion of olanzapine- treated patients who had clinically significant weight gain were greater than in short-term studies. The percentage of patients who gained ≥ 25% of their baseline body weight with long-term exposure was very common (≥ 10%).
Hyperglycaemia:
As with some other antipsychotics, exacerbation of pre-existing diabetes and hyperglycaemia have been reported rarely and diabetic ketoacidosis and diabetic coma including some fatal cases have been reported very rarely during the use of ZYPREXA, sometimes in patients with no reported history of hyperglycaemia (see 8 ADVERSE REACTIONS; Post-Market Adverse Drug Reactions section).
In some cases, a prior increase in body weight has been reported which may be a predisposing factor. Patients should have baseline and periodic monitoring of blood glucose and body weight. In clinical trials (up to 52 weeks) olanzapine was associated with a greater mean change in glucose relative to placebo.
Treatment-emergent clinically significant changes in fasting glucose were observed in patients with or without evidence of glucose dysregulation at baseline (see 8 ADVERSE REACTIONS, Other Adverse Events Observed During Clinical Trials with Oral and Intramuscular Olanzapine Across All Indications, Glucose Changes).
Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population.
Given these confounders, the relationship between atypical antipsychotic use and hyperglycemia-related adverse events is not completely understood. However, epidemiological studies suggest an increased risk of treatment-emergent hyperglycemia-related adverse events in patients treated with the atypical antipsychotics.
Precise risk estimates for hyperglycemia-related adverse events in patients treated with atypical antipsychotics are not available. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness.
Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the suspect drug.
, obesity, family history of diabetes) who are starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment. Patients with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics should be monitored regularly for worsening of glucose control.
ZYPREXA Olanzapine / Olanzapine Tartrate Page 13 of 75 Hyperprolactinemia:
As with other drugs that block dopamine D2 and/or serotonin 5-HT2 receptors, olanzapine may elevate prolactin levels. Elevations associated with ZYPREXA treatment are generally mild, and may decline during continued administration. Since tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin- dependent in vitro, ZYPREXA should only be administered to patients with previously detected breast cancer if the benefits outweigh the potential risks.
Caution should also be exercised when considering ZYPREXA treatment in patients with pituitary tumours. Possible manifestations associated with elevated prolactin levels are amenorrhea, galactorrhea, and menorrhagia. As is common with compounds which stimulate prolactin release, the administration of olanzapine resulted in an increase in the incidence of mammary neoplasms in both rats and mice.
The physiological differences between rats and humans with regard to prolactin make the clinical significance of these findings unclear. To date, neither clinical nor epidemiological studies have shown an association between chronic administration of these drugs and mammary tumorigenesis.
Long-standing hyperprolactinemia when associated with hypogonadism may […]
CAOfficial regulatory label· Warnings and precautions· revised March 24, 2026[2]
, Special Populations, Use in Geriatric Patients with Dementia). 4. 1 Special Populations). Given the limited experience with ZYPREXA in the elderly, and the higher incidence of concomitant illness and concomitant medication in this population, ZYPREXA should be used with caution.
, nonsmoking female patients), or who may be pharmacodynamically more sensitive to ZYPREXA. When indicated, dose escalation should be performed with caution in these patients.
Patients with Hepatic and/or Renal Impairment:
As clinical experience is lacking in these patients, the lower initial starting dose and slower titration to initial target dose should be considered. 1 Special Populations). 5 mg) should be considered when clinical factors warrant. 2 Recommended Dose and Dosage Adjustment ORAL ADMINISTRATION Bioequivalence of the 15 mg and 20 mg tablets to multiple 5 mg tablets has been demonstrated.
These tablet formulations are equally well absorbed and can be readily interchanged. Pharmacokinetic studies showed that the ZYPREXA Tablets and ZYPREXA ZYDIS dosage forms are bioequivalent. ZYPREXA ZYDIS orally disintegrating tablets can be used as an alternative to ZYPREXA Tablets.
2 Study results ). ZYPREXA Olanzapine / Olanzapine Tartrate Page 6 of 75 Schizophrenia and Related Disorders Adults: ZYPREXA (olanzapine) should be administered on a once-a-day schedule without regard to meals, generally beginning with 5 to 10 mg, with a target dose of 10 mg/day within several days.
Further dosage adjustments, if indicated, should generally occur at intervals of not less than 1 week, since steady state for ZYPREXA would not be achieved for approximately 1 week in the typical patient. When dosage adjustments are necessary, dose increments/ decrements of 5 mg per day are recommended.
, to a dose of 15 mg/day or greater) is normally recommended only after clinical assessment. In clinical trials a dose range of 5-20 mg/day was studied (see 14 CLINICAL TRIALS). Doses above 20 mg/day have been evaluated from a safety perspective (see Table 6 in Adverse Events, Dose- Dependent Adverse Events subsection); however, efficacy at doses above 20 mg/day has not been systematically evaluated.
This is not medical advice. Consult a qualified healthcare professional.
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. 5 ) Efficacy was established with Symbyax (olanzapine and fluoxetine in combination); refer to the product label for Symbyax. Treatment of treatment resistant depression.
6 ) Efficacy was established with Symbyax (olanzapine and fluoxetine in combination) in adults; refer to the product label for Symbyax. 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.
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. 5 ] . 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. 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.
5 ] . Adjunctive Therapy to Lithium or Valproate — Oral olanzapine is indicated for the treatment of manic or mixed episodes associated with bipolar I disorder as an adjunct to lithium or valproate. Efficacy was established in two 6-week clinical trials in adults.
2 )] . 3 Special Considerations in Treating Pediatric Schizophrenia and Bipolar I Disorder Pediatric schizophrenia and bipolar I disorder are serious mental disorders; however, diagnosis can be challenging. For pediatric schizophrenia, symptom profiles can be variable, and for bipolar I disorder, pediatric patients may have variable patterns of periodicity of manic or mixed symptoms.
It is recommended that medication therapy for pediatric schizophrenia and bipolar I disorder be initiated only after a thorough diagnostic evaluation has been performed and careful consideration given to the risks associated with medication treatment.
Medication treatment for both pediatric schizophrenia and bipolar I disorder should be part of a total treatment program that often includes psychological, educational and social interventions. 5 Olanzapine and Fluoxetine in Combination: Depressive Episodes Associated with Bipolar I Disorder Oral olanzapine and fluoxetine in combination is indicated for the treatment of depressive episodes associated with bipolar I disorder, based on clinical studies.
When using olanzapine and fluoxetine in combination, refer to the Clinical Studies section of the package insert for Symbyax. Olanzapine monotherapy is not indicated for the treatment of depressive episodes associated with bipolar I disorder.
6 Olanzapine and Fluoxetine in Combination: Treatment Resistant Depression Oral olanzapine and fluoxetine in combination is indicated for the treatment of treatment resistant depression (major depressive disorder in patients who do not respond to 2 separate trials of different antidepressants of adequate dose and duration in the current episode), based on clinical studies in adult patients.
When using olanzapine and fluoxetine in combination, refer to the Clinical Studies section of the package insert for Symbyax. Olanzapine monotherapy is not indicated for the treatment of treatment resistant depression.
How to take
USOfficial regulatory label· revised July 10, 2023[3]
6 ) Oral in combination with fluoxetine: Start at 5 mg of 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.
1 ) Olanzapine may be given without regard to meals. 1 ) Olanzapine and Fluoxetine in Combination: Dosage adjustments, if indicated, should be made with the individual components according to efficacy and tolerability. 6 ) Olanzapine monotherapy is not indicated for the treatment of depressive episodes associated with bipolar I disorder or treatment resistant depression.
6 ) Safety of co-administration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated in adults. 6 ) Safety of co-administration of doses above 12 mg olanzapine with 50 mg fluoxetine has not been evaluated in children and adolescents ages 10 to 17.
1 Schizophrenia Adults Dose Selection — Oral olanzapine should be administered on a once-a-day schedule without regard to meals, generally beginning with 5 mg to 10 mg initially, with a target dose of 10 mg/day within several days.
Further dosage adjustments, if indicated, should generally occur at intervals of not less than 1 week, since steady state for olanzapine would not be achieved for approximately 1 week in the typical patient. When dosage adjustments are necessary, dose increments/decrements of 5 mg QD are recommended.
Efficacy in schizophrenia was demonstrated in a dose range of 10 mg/day to 15 mg/day in clinical trials. However, doses above 10 mg/day were not demonstrated to be more efficacious than the 10 mg/day dose. , to a dose of 15 mg/day or greater) is recommended only after clinical assessment.
Olanzapine is not indicated for use in doses above 20 mg/day. 3 )] . When indicated, dose escalation should be performed with caution in these patients. 1 )] . The healthcare provider who elects to use olanzapine for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.
5 mg or 5 mg, with a target dose of 10 mg/day. 1 mg/day). 5 mg or 5 mg are recommended. 1 )] . Maintenance Treatment — The efficacy of olanzapine for the maintenance treatment of schizophrenia in the adolescent population has not been systematically evaluated; however, maintenance efficacy can be extrapolated from adult data along with comparisons of olanzapine pharmacokinetic parameters in adult and adolescent patients.
Thus, it is generally recommended that responding patients be continued beyond the acute response, but at the lowest dose needed to maintain remission. Patients should be periodically reassessed to determine the need for maintenance treatment.
2 Bipolar I Disorder (Manic or Mixed Episodes) Adults Dose Selection for Monotherapy — Oral olanzapine should be administered on a once-a-day schedule without regard to meals, generally beginning with 10 mg or 15 mg. Dosage adjustments, if indicated, should generally occur at intervals of not less than 24 hours, reflecting the procedures in the placebo-controlled trials.
When dosage adjustments are necessary, dose increments/decrements of 5 mg QD are recommended. Short-term (3-4 weeks) antimanic efficacy was demonstrated in a dose range of 5 mg to 20 mg/day in clinical trials. 2 )] . 2 )] . The healthcare provider who elects to use olanzapine for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.
Dose Selection for Adjunctive Treatment — When administered as adjunctive treatment to lithium or valproate, oral olanzapine dosing should generally begin with 10 mg once-a-day without regard to meals. 2 )] . The safety of doses above 20 mg/day has not been evaluated in clinical trials.
5 mg or 5 mg, with a target dose of 10 mg/day. 9 mg/day). 5 mg or 5 mg are recommended. 2 )] . Maintenance Treatment — The efficacy of olanzapine for the maintenance treatment of bipolar I disorder in the adolescent population has not been evaluated; however, maintenance efficacy can be extrapolated from adult data along with comparisons of olanzapine pharmacokinetic parameters in adult and adolescent patients.
Thus, it is generally recommended that responding patients be continued beyond the acute response, but at the lowest dose needed to maintain remission. Patients should be periodically reassessed to determine the need for maintenance treatment.
3 Administration of Olanzapine Orally Disintegrating Tablets Peel back foil on blister. Do not push tablet through foil. Immediately upon opening the blister or the bottle, using dry hands, remove tablet and place entire olanzapine orally disintegrating tablet in the mouth.
Tablet disintegration occurs rapidly in saliva so it can be easily swallowed with or without liquid. 5 Olanzapine and Fluoxetine in Combination: Depressive Episodes Associated with Bipolar I Disorder When using olanzapine and fluoxetine in combination, also refer to the Clinical Studies section of the package insert for Symbyax.
Adults Oral olanzapine should be administered in combination with fluoxetine once daily in the evening, without regard to meals, generally beginning with 5 mg of oral olanzapine and 20 mg of fluoxetine. 5 mg and fluoxetine 20 mg to 50 mg.
Antidepressant efficacy was demonstrated with olanzapine and fluoxetine in combination in adult patients with a dose range of olanzapine 6 mg to 12 mg and fluoxetine 25 mg to 50 mg. Safety of co-administration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated in clinical studies.
5 mg of oral olanzapine and 20 mg of fluoxetine. Dosage adjustments, if indicated, can be made according to efficacy and tolerability. Safety of co-administration of doses above 12 mg olanzapine with 50 mg fluoxetine has not been evaluated in pediatric clinical studies.
Safety and efficacy of olanzapine and fluoxetine in combination was determined in clinical trials supporting approval of Symbyax (fixed dose combination of olanzapine and fluoxetine). Symbyax is dosed between 3 mg/25 mg (olanzapine/fluoxetine) per day and 12 mg/50 mg (olanzapine/fluoxetine) per day.
The following table demonstrates the appropriate individual component doses of olanzapine and fluoxetine versus Symbyax. Dosage adjustments, if indicated, should be made with the individual components according to efficacy and tolerability.
Table 1:
Approximate Dose Correspondence Between Symbyax a and the Combination of Olanzapine and Fluoxetine a Symbyax (olanzapine/fluoxetine HCl) is a fixed-dose combination of olanzapine and fluoxetine. 5 40+10 While there is no body of evidence to answer the question of how long a patient treated with olanzapine and fluoxetine in combination should remain on it, it is generally accepted that bipolar I disorder, including the depressive episodes associated with bipolar I disorder, is a chronic illness requiring chronic treatment.
The healthcare provider should periodically reexamine the need for continued pharmacotherapy. Olanzapine monotherapy is not indicated for the treatment of depressive episodes associated with bipolar I disorder. 6 Olanzapine and Fluoxetine in Combination: Treatment Resistant Depression When using olanzapine and fluoxetine in combination, also refer to the Clinical Studies section of the package insert for Symbyax.
Oral olanzapine should be administered in combination with fluoxetine once daily in the evening, without regard to meals, generally beginning with 5 mg of oral olanzapine and 20 mg of fluoxetine. Dosage adjustments, if indicated, can be made according to efficacy and tolerability within dose ranges of oral olanzapine 5 mg to 20 mg and fluoxetine 20 mg to 50 mg.
Antidepressant efficacy was demonstrated with olanzapine and fluoxetine in combination in adult patients with a dose range of olanzapine 6 mg to 18 mg and fluoxetine 25 mg to 50 mg. Safety and efficacy of olanzapine in combination with fluoxetine was determined in clinical trials supporting approval of Symbyax (fixed dose combination of olanzapine and fluoxetine).
Symbyax is dosed between 3 mg/25 mg (olanzapine/fluoxetine) per day and 12 mg/50 mg (olanzapine/fluoxetine) per day. Table 1 above demonstrates the appropriate individual component doses of olanzapine and fluoxetine versus Symbyax. Dosage adjustments, if indicated, should be made with the individual components according to efficacy and tolerability.
While there is no body of evidence to answer the question of how long a patient treated with olanzapine and fluoxetine in combination should remain on it, it is generally accepted that treatment resistant depression (major depressive disorder in adult patients who do not respond to 2 separate trials of different antidepressants of adequate dose and duration in the current episode) is a chronic illness requiring chronic treatment.
The healthcare provider should periodically reexamine the need for continued pharmacotherapy. Safety of co-administration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated in clinical studies. Olanzapine monotherapy is not indicated for treatment of treatment resistant depression (major depressive disorder in patients who do not respond to 2 antidepressants of adequate dose and duration in the current episode).
5 mg to 5 mg with fluoxetine 20 mg should be used for patients with a predisposition to hypotensive reactions, patients with hepatic impairment, or patients who exhibit a combination of factors that may slow the metabolism of olanzapine or fluoxetine in combination (female gender, geriatric age, nonsmoking status), or those patients who may be pharmacodynamically sensitive to olanzapine.
Dosing modification may be necessary in patients who exhibit a combination of factors that may slow metabolism. When indicated, dose escalation should be performed with caution in these patients. 3 )] .
This is not medical advice. Consult a qualified healthcare professional.
Most-reported reactions to the US regulator (12 mo to June 4, 2026): 5,952 reports total. [5]
Off Label Use 619
Drug Ineffective 473
Nausea 360
Vomiting 324
Toxicity To Various Agents 293
Somnolence 247
Drug Interaction 243
Weight Increased 243
Fatigue 219
Condition Aggravated 210
Intentional Overdose 205
Neuroleptic Malignant Syndrome 199
Side effects & warnings
USOfficial regulatory label· Adverse reactions· revised July 10, 2023[3]
6 ADVERSE REACTIONS When using olanzapine and fluoxetine in combination, also refer to the Adverse Reactions section of the package insert for Symbyax. 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 Lannett Company, Inc. 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 4765 patient-years of exposure to olanzapine plus 722 patients with exposure to intramuscular olanzapine for injection.
This database includes: (1) 2500 patients who participated in multiple-dose oral olanzapine premarketing trials in schizophrenia and Alzheimer's disease representing approximately 1122 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 participated in an oral olanzapine trial of patients having various psychiatric symptoms in association with Alzheimer's disease representing approximately 29 patient-years of exposure; (4)5788 additional patients from 88 oral olanzapine clinical trials as of December 31, 2001; (5) 1843 additional patients from 41 olanzapine clinical trials as of October 31, 2011; and (6) 722 patients who participated in intramuscular olanzapine for injection premarketing trials in agitated patients with schizophrenia, bipolar I disorder (manic or mixed episodes), or dementia.
Also included below is information from the premarketing 6-week clinical study database for olanzapine in combination with lithium or valproate, consisting of 224 patients who participated in bipolar I disorder (manic or mixed episodes) trials with approximately 22 patient-years of exposure.
The conditions and duration of treatment with olanzapine varied greatly and included (in overlapping categories) open-label and double-blind phases of studies, inpatients and outpatients, fixed-dose and dose-titration studies, and short-term or longer-term exposure.
Adverse reactions were assessed by collecting adverse reactions, results of physical examinations, vital signs, weights, laboratory analytes, ECGs, chest x-rays, and results of ophthalmologic examinations. Certain portions of the discussion below relating to objective or numeric safety parameters, namely, dose-dependent adverse reactions, vital sign changes, weight gain, laboratory changes, and ECG changes are derived from studies in patients with schizophrenia and have not been duplicated for bipolar I disorder (manic or mixed episodes) or agitation.
However, this information is also generally applicable to bipolar I disorder (manic or mixed episodes) and agitation. Adverse reactions during exposure were obtained by spontaneous report and recorded by clinical investigators using terminology of their own choosing.
Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse reactions without first grouping similar types of reactions into a smaller number of standardized reaction categories.
In the tables and tabulations that follow, MedDRA and COSTART Dictionary terminology has been used to classify reported adverse reactions. The stated frequencies of adverse reactions represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse reaction of the type listed.
A reaction was considered treatment emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. The reported reactions do not include those reaction terms that were so general as to be uninformative.
Reactions listed elsewhere in labeling may not be repeated below. It is important to emphasize that, although the reactions occurred during treatment with olanzapine, they were not necessarily caused by it. The entire label should be read to gain a complete understanding of the safety profile of olanzapine.
The prescriber should be aware that the figures in the tables and tabulations cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials.
Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing healthcare provider with some basis for estimating the relative contribution of drug and nondrug factors to the adverse reactions incidence in the population studied.
Incidence of Adverse Reactions in Short-Term, Placebo-Controlled and Combination Trials The following findings are based on premarketing trials of oral olanzapine for schizophrenia, bipolar I disorder (manic or mixed episodes), a subsequent trial of patients having various psychiatric symptoms in association with Alzheimer's disease, and premarketing combination trials.
Adverse Reactions Associated with Discontinuation of Treatment in Short-Term, Placebo-Controlled Trials Schizophrenia — Overall, there was no difference in the incidence of discontinuation due to adverse reactions (5% for oral olanzapine vs 6% for placebo).
However, discontinuations due to increases in ALT were considered to be drug related (2% for oral olanzapine vs 0% for placebo). Bipolar I Disorder (Manic or Mixed Episodes) Monotherapy — Overall, there was no difference in the incidence of discontinuation due to adverse reactions (2% for oral olanzapine vs 2% for placebo).
Adverse Reactions Associated with Discontinuation of Treatment in Short-Term Combination Trials Bipolar I Disorder (Manic or Mixed Episodes), Olanzapine as Adjunct to Lithium or Valproate — In a study of patients who were already tolerating either lithium or valproate as monotherapy, discontinuation rates due to adverse reactions were 11% for the combination of oral olanzapine with lithium or valproate compared to 2% for patients who remained on lithium or valproate monotherapy.
Discontinuations with the combination of oral olanzapine and lithium or valproate that occurred in more than 1 patient were: somnolence (3%), weight gain (1%), and peripheral edema (1%). Commonly Observed Adverse Reactions in Short-Term, Placebo-Controlled Trials The most commonly observed adverse reactions associated with the use of oral olanzapine (incidence of 5% or greater) and not observed at an equivalent incidence among placebo-treated patients (olanzapine incidence at least twice that for placebo) were: Table 9: Common Treatment-Emergent Adverse Reactions Associated with the Use of Oral Olanzapine in 6-Week Trials — SCHIZOPHRENIA a Personality disorder is the COSTART term for designating nonaggressive objectionable behavior.
5 mg/day) and with incidence greater than placebo who participated in the acute phase of placebo-controlled trials.
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) Body as a Whole Accidental injury 12 8 Asthenia 10 9 Fever 6 2 Back pain 5 2 Chest pain 3 1 Cardiovascular System Postural hypotension 3 1 Tachycardia 3 1 Hypertension 2 1 Digestive System Dry mouth 9 5 Constipation 9 4 Dyspepsia 7 5 Vomiting 4 3 Increased appetite 3 2 Hemic and Lymphatic System Ecchymosis 5 3 Metabolic and Nutritional Disorders Weight gain 5 3 Peripheral edema 3 1 Musculoskeletal System Extremity pain (other than joint) 5 3 Joint pain 5 3 Nervous System Somnolence 29 13 Insomnia 12 11 Dizziness 11 4 Abnormal gait 6 1 Tremor 4 3 Akathisia 3 2 Hypertonia 3 2 Articulation impairment 2 1 Respiratory System Rhinitis 7 6 Cough increased 6 3 Pharyngitis 4 3 Special Senses Amblyopia 3 2 Urogenital System Urinary incontinence 2 1 Urinary tract infection 2 1 Dose Dependency of Adverse Reactions A dose group difference has been observed for fatigue, dizziness, weight gain and prolactin elevation.
6%) was observed with significant differences between 10 mg/day vs 40 mg/day and 20 mg/day vs 40 mg/day. 6%) was observed with significant differences between 20 mg vs 40 mg. 15 )] . The following table addresses dose relatedness for other adverse reactions using data from a schizophrenia trial involving fixed dosage ranges of oral olanzapine.
It enumerates the percentage of patients with treatment-emergent adverse reactions for the 3 fixed-dose range groups and placebo. The data were analyzed using the Cochran-Armitage test, excluding the placebo group, and the table includes only those adverse reactions for which there was a trend.
5 mg/day Adverse Reaction (N=68) (N=65) (N=64) (N=69) Asthenia 15 8 9 20 Dry mouth 4 3 5 13 Nausea 9 0 2 9 Somnolence 16 20 30 39 Tremor 3 0 5 7 Commonly Observed Adverse Reactions in Short-Term Trials of Oral Olanzapine as Adjunct to Lithium or Valproate In the bipolar I disorder (manic or mixed episodes) adjunct placebo-controlled trials, the most commonly observed adverse reactions associated with the combination of olanzapine and lithium or valproate (incidence of ≥5% and at least twice placebo) were: Table 13: Common Treatment-Emergent Adverse Reactions Associated with the Use of Oral Olanzapine in 6-Week Adjunct to Lithium or Valproate 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) Dry mouth 32 9 Weight gain 26 7 Increased appetite 24 8 Dizziness 14 7 Back pain 8 4 Constipation 8 4 Speech disorder 7 1 Increased salivation 6 2 Amnesia 5 2 Paresthesia 5 2 Adverse Reactions Occurring at an Incidence of 2% or More among Oral Olanzapine-Treated Patients in Short-Term Trials of Olanzapine as Adjunct to Lithium or Valproate Table 14 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse reactions that occurred in 2% or more of patients treated with the combination of olanzapine (doses ≥5 mg/day) and lithium or valproate and with incidence greater than lithium or valproate alone who participated in the acute phase of placebo-controlled combination trials.
Table 14:
Treatment-Emergent Adverse Reactions: Incidence in Short-Term, Placebo-Controlled Clinical Trials of Oral Olanzapine as Adjunct to Lithium or Valproate a Denominator used was for females only (olanzapine, N=128; placebo, N=51). Body System/Adverse Reaction Percentage of Patients Reporting Event Olanzapine with lithium or valproate (N=229) Placebo with lithium or valproate (N=115) Body as a Whole Asthenia 18 13 Back pain 8 4 Accidental injury 4 2 Chest pain 3 2 Cardiovascular System Hypertension 2 1 Digestive System Dry mouth 32 9 Increased appetite 24 8 Thirst 10 6 Constipation 8 4 Increased salivation 6 2 Metabolic and Nutritional Disorders Weight gain 26 7 Peripheral edema 6 4 Edema 2 1 Nervous System Somnolence 52 27 Tremor 23 13 Depression 18 17 Dizziness 14 7 Speech disorder 7 1 Amnesia 5 2 Paresthesia 5 2 Apathy 4 3 Confusion 4 1 Euphoria 3 2 Incoordination 2 0 Respiratory System Pharyngitis 4 1 Dyspnea 3 1 Skin and Appendages Sweating 3 1 Acne 2 0 Dry skin 2 0 Special Senses Amblyopia 9 5 Abnormal vision 2 0 Urogenital System Dysmenorrhea a 2 0 Vaginitis a 2 0 For specific information about the adverse reactions observed with lithium or valproate, refer to the Adverse Reactions section of the package inserts for these other products.
Extrapyramidal Symptoms The following table enumerates the percentage of patients with treatment-emergent extrapyramidal symptoms as assessed by categorical analyses of formal rating scales during acute therapy in a controlled clinical trial comparing oral olanzapine at 3 fixed doses with placebo in the treatment of schizophrenia in a 6-week trial.
Table 16:
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 a Percentage of patients with a Simpson-Angus Scale total score >3.
b Percentage of patients with a Barnes Akathisia Scale global score ≥2. 5 mg/day Parkinsonism a 15 14 12 14 Akathisia b 23 16 19 27 The following table enumerates the percentage of patients with treatment-emergent extrapyramidal symptoms as assessed by spontaneously reported adverse reactions during acute therapy in the same controlled clinical trial comparing olanzapine at 3 fixed doses with placebo in the treatment of schizophrenia in a 6-week trial.
Table 17:
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 a Patients with the following COSTART terms were counted in this category: dystonia, generalized spasm, neck rigidity, oculogyric crisis, opisthotonos, torticollis.
b Patients with the following COSTART terms were counted in this category: akinesia, cogwheel rigidity, extrapyramidal syndrome, hypertonia, hypokinesia, masked facies, tremor. c Patients with the following COSTART terms were counted in this category: akathisia, hyperkinesia.
d Patients with the following COSTART terms were counted in this category: buccoglossal syndrome, choreoathetosis, dyskinesia, tardive dyskinesia. e Patients with the following COSTART terms were counted in this category: movement disorder, myoclonus, twitching.
5 mg/day to 20 mg/day). 0. Percentage of Patients Reporting Event Placebo Olanzapine Categories a (N=89) (N=179) Dystonic events 0 1 Parkinsonism events 2 1 Akathisia events 4 6 Dyskinetic events 0 1 Nonspecific events 0 4 Any extrapyramidal event 6 10 Dystonia, Class Effect: Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment.
Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, the frequency and severity are greater with high potency and at higher doses of first generation antipsychotic drugs.
In general, an elevated risk of acute dystonia may be observed in males and younger age groups receiving antipsychotics; however, events of dystonia have been reported infrequently (<1%) with olanzapine use. Other Adverse Reactions Other Adverse Reactions Observed During the Clinical Trial Evaluation of Oral Olanzapine Following is a list of treatment-emergent adverse reactions reported by patients treated with oral olanzapine (at multiple doses ≥1 mg/day) in clinical trials.
This listing is not intended to include reactions (1) already listed in previous tables or elsewhere in labeling, (2) for which a drug cause was remote, (3) which were so general as to be uninformative, (4) which were not considered to have significant clinical implications, or (5) which occurred at a rate equal to or less than placebo.
Reactions are classified by body system using the following definitions: frequent adverse reactions are those occurring in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1000 patients; rare reactions are those occurring in fewer than 1/1000 patients.
Body as a Whole — Infrequent: chills, face edema, photosensitivity reaction, suicide attempt 1 ; Rare: chills and fever, hangover effect, sudden death 1 . Cardiovascular System — Infrequent: cerebrovascular accident, vasodilatation.
Digestive System — Infrequent: abdominal distension, nausea and vomiting, tongue edema; Rare: ileus, intestinal obstruction, liver fatty deposit. Hemic and Lymphatic System — Infrequent: thrombocytopenia. Metabolic and Nutritional Disorders — Frequent: alkaline phosphatase increased; Infrequent: bilirubinemia, hypoproteinemia.
Musculoskeletal System — Rare: osteoporosis. Nervous System — Infrequent: ataxia, dysarthria, libido decreased, stupor; Rare: coma. Respiratory System — Infrequent: epistaxis; Rare: lung edema. Skin and Appendages — Infrequent: alopecia.
1 These terms represent serious adverse events but do not meet the definition for adverse drug reactions. They are included here because of their seriousness. 2 Adjusted for gender.
USOfficial regulatory label· Warnings and precautions· revised July 10, 2023[3]
5 WARNINGS AND PRECAUTIONS When using olanzapine and fluoxetine in combination, also refer to the Warnings and Precautions section of the package insert for Symbyax. , stroke, transient ischemic attack). 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.
2 ) Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring. 3 ) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Discontinue if DRESS is suspected. 4 ) Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes including hyperglycemia, dyslipidemia, and weight gain.
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 ) 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 ) Weight Gain: Potential consequences of weight gain should be considered.
Patients should receive regular monitoring of weight. 5 ) Tardive Dyskinesia: Discontinue if clinically appropriate. 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. 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.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
USOfficial regulatory label· Contraindications· revised July 10, 2023[3]
4 CONTRAINDICATIONS 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.
( 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 )
This is not medical advice. Consult a qualified healthcare professional.
The recommended starting dose for olanzapine is 10 mg/day. 1).
Preventing recurrence in bipolar disorder:
The recommended starting dose is 10 mg/day. For patients who have been receiving olanzapine for treatment of manic episode, continue therapy for preventing recurrence at the same dose. If a new manic, mixed, or depressive episode occurs, olanzapine treatment should be continued (with dose optimisation as needed), with supplementary therapy to treat mood symptoms, as clinically indicated.
During treatment for schizophrenia, manic episode and recurrence prevention in bipolar disorder, daily dosage may subsequently be adjusted on the basis of individual clinical status within the range 5-20 mg/day. An increase to a dose greater than the recommended starting dose is advised only after appropriate clinical reassessment and should generally occur at intervals of not less than 24 hours.
Olanzapine can be given without regards for meals as absorption is not affected by food. Gradual tapering of the dose should be considered when discontinuing olanzapine. 3 Olazax Disperzi orodispersible tablets should be placed in the mouth, where it will rapidly disperse in saliva, so it can be easily swallowed.
Alternatively, it may be dispersed in a full glass of water or other suitable beverage (orange juice, apple juice, milk or coffee) immediately before the administration. 4). Renal and/or hepatic impairment A lower starting dose (5 mg) should be considered for such patients.
In cases of moderate hepatic insufficiency (cirrhosis, Child-Pugh Class A or B), the starting dose should be 5 mg and only increased with caution. Smokers The starting dose and dose range need not be routinely altered for non-smokers relative to smokers.
The metabolism of olanzapine may be induced by smoking. 5). When more than one factor is present which might result in slower metabolism (female gender, geriatric age, non-smoking status), consideration should be given to decreasing the starting dose.
Dose escalation, when indicated, should be conservative in such patients. ) Paediatric population Olanzapine is not recommended for use in children and adolescents below 18 years of age due to a lack of data on safety and efficacy. 2).
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
EUOfficial regulatory label· Adverse reactions· revised May 12, 2026[4]
4), rash, asthenia, fatigue, pyrexia, arthralgia, increased alkaline phosphatase, high gamma glutamyltransferase, high uric acid, high creatine phosphokinase and oedema. Tabulated list of adverse reactions The following table lists the adverse reactions and laboratory investigations observed from spontaneous reporting and in clinical trials.
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
The frequency terms listed are defined as follows:
Very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 10,000), not known (cannot be estimated from the data available). 6) Reproductive system and breast disorders Erectile dysfunction in males Decreased libido in males and females Amenorrhea Breast enlargement Galactorrhea in females Gynaecomastia/breast enlargement in males Priapism12 General disorders and administration site conditions Asthenia 10 Fatigue Oedema Pyrexia10 Investigations Elevated plasma prolactin levels 8 Increased alkaline phosphatase10 High creatine phosphokinase11 High Gamma Glutamyltransferas e10 High uric acid 10 Increased total bilirubin 1 Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) categories.
8%). 3 % respectively). 2 Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were greater in patients without evidence of lipid dysregulation at baseline. 2 mmol/l). 2 mmol/l) were very common.
56 mmol/l) which increased to high (≥ 7 mmol/l). 56 - < 7 mmol/l) to high (≥ 7 mmol/l) were very common. 26 mmol/l). 26 mmol/l) were very common. 6 In clinical trials, the incidence of Parkinsonism and dystonia in olanzapine-treated patients was numerically higher, but not statistically significantly different from placebo.
Olanzapine-treated patients had a lower incidence of Parkinsonism, akathisia and dystonia compared with titrated doses of haloperidol. In the absence of detailed information on the pre-existing history of individual acute and tardive extrapyramidal movement disorders, it can not be concluded at present that olanzapine produces less tardive dyskinesia and/or other tardive extrapyramidal syndromes.
7 Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea and vomiting have been reported when olanzapine is stopped abruptly. 8 In clinical trials of up to 12 weeks, plasma prolactin concentrations exceeded the upper limit of normal range in approximately 30% of olanzapine treated patients with normal baseline prolactin value.
[…]
EUOfficial regulatory label· Warnings and precautions· revised May 12, 2026[4]
During antipsychotic treatment, improvement in the patient's clinical condition may take several days to some weeks. Patients should be closely monitored during this period. Dementia-related psychosis and/or behavioural disturbances Olanzapine is not recommended for use patients with dementia-related psychosis and/or behavioural disturbances because of an increase in mortality and the risk of cerebrovascular accident.
5 %, respectively). 4 mg) or duration of treatment. , pneumonia, with or without aspiration), or concomitant use of benzodiazepines. However, the incidence of death was higher in olanzapine-treated than in placebo-treated patients independent of these risk factors.
, stroke, transient ischemic attack), including fatalities, were reported. 4 %, respectively). All olanzapine and placebo-treated patients who experienced a cerebrovascular event had pre-existing risk factors. Age > 75 years and vascular/mixed type dementia were identified as risk factors for CVAE in association with olanzapine treatment.
The efficacy of olanzapine was not established in these trials. Parkinson's disease The use of olanzapine in the treatment of dopamine agonist associated psychosis in patients with Parkinson's disease is not recommended. 8), and olanzapine was not more effective than placebo in the treatment of psychotic symptoms.
In these trials, patients were initially required to be stable on the lowest effective dose of anti- Parkinsonian medicinal products (dopamine agonist) and to remain on the same anti-Parkinsonian medicinal products and dosages throughout the study.
5 mg/day and titrated to a maximum of 15 mg/day based on investigator judgement. Neuroleptic Malignant Syndrome (NMS) NMS is a potentially life-threatening condition associated with antipsychotic medicinal products. Rare cases reported as NMS have also been received in association with 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 creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
EUOfficial regulatory label· Contraindications· revised May 12, 2026[4]
1. Patients with known risk of narrow-angle glaucoma.
This is not medical advice. Consult a qualified healthcare professional.
If a patient develops signs and symptoms indicative of NMS, or presents with unexplained high fever without additional clinical manifestations of NMS, all antipsychotic medicines, including olanzapine must be discontinued. 8). In some cases, a prior increase in body weight has been reported which may be a predisposing factor.
g. measuring of blood glucose at baseline, 12 weeks after starting olanzapine treatment and annually thereafter. Patients treated with any antipsychotic medicines, including Olanzapine SUN, should be observed for signs and symptoms of hyperglycaemia (such as polydipsia, polyuria, polyphagia, and weakness) and patients with diabetes mellitus or with risk factors for diabetes mellitus should be monitored regularly for worsening of glucose control.
g. at baseline, 4, 8 and 12 weeks after starting olanzapine treatment and quarterly thereafter. 8). Lipid alterations should be managed as clinically appropriate, particularly in dyslipidemic patients and in patients with risk factors for the development of lipids disorders.
g. at baseline, 12 weeks after starting olanzapine treatment and every 5 years thereafter. Anticholinergic activity While olanzapine demonstrated anticholinergic activity in vitro, experience during the clinical trials revealed a low incidence of related events.
However, as clinical experience with olanzapine in patients with concomitant illness is limited, caution is advised when prescribing for patients with prostatic hypertrophy, or paralytic ileus and related conditions. Hepatic function Transient, asymptomatic elevations of hepatic aminotransferases, ALT, AST have been seen commonly, especially in early treatment.
Caution should be exercised and follow-up organised in patients with elevated ALT and/or AST, in patients with signs and symptoms of hepatic impairment, in patients with pre-existing conditions associated with limited hepatic functional reserve, and in patients who are being treated with potentially hepatotoxic medicines.
In cases where hepatitis (including hepatocellular, cholestatic or mixed liver injury) has been diagnosed, olanzapine […]
Maintenance Therapy in Schizophrenia:
It is recommended that responding patients with schizophrenia be continued on ZYPREXA at the lowest dose needed to maintain remission. Patients should be reassessed periodically to determine the need for maintenance treatment. While there is no body of evidence available to answer the question of how long the patient should be treated with ZYPREXA, the effectiveness of maintenance treatment is well established for many other antipsychotic drugs.
Bipolar Disorder Bipolar Mania Adults:
The recommended starting dose for olanzapine is 15 mg administered once a day in monotherapy and 10 mg daily in combination therapy. It may be given without regard to meals as its absorption is not affected by food. The dosage range of olanzapine is from 5 mg to 20 mg per day.
Daily dosage should be adjusted in response to clinical assessment.
Maintenance Therapy in Bipolar Disorder:
Patients who have been receiving and responding to ZYPREXA for the treatment of acute manic or mixed episodes of bipolar disorder should initially continue maintenance therapy at the same dose (see 14 CLINICAL TRIALS). Subsequent daily dosage should be adjusted on the basis of clinical status within a range of 5-20 mg per day.
Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment. Health Canada has not authorized an indication for pediatric use. 5 mg and 10 mg of intramuscular olanzapine for injection have been shown to be effective in controlling agitation in patients with schizophrenia (see 14 CLINICAL TRIALS).
Individual doses of more than 10 mg of intramuscular olanzapine have not been studied and are not recommended.
Usual Dose for Agitated Patients with Schizophrenia and Bipolar Mania:
The usual initial dose for olanzapine injection is 10 mg, administered as a single intramuscular injection. 5 mg) may be given, on the basis of individual clinical status.
Repeat and Maximum Dose:
In clinical trials over a 24 hour period, a minority of patients required a second dose, and only a small percent of patients required a third dose of ZYPREXA IntraMuscular (see 14 CLINICAL TRIALS). Thus safety information on the use of repeated doses of ZYPREXA IntraMuscular is limited.
Nevertheless, if warranted by the clinical situation, a second dose, 5-10 mg, may be administered 2 hours after the first injection. A third dose, if required, should be ZYPREXA Olanzapine / Olanzapine Tartrate Page 7 of 75 given no sooner than four hours after the second dose.
The safety of total daily doses greater than 30 mg has not been evaluated in clinical trials. The recommended maximum daily dose of olanzapine (oral and IM) is 20 mg, with no more than three injections in a 24 hour period. Zyprexa IntraMuscular is intended for intramuscular use only.
Do […]
9 ) Seizures: Use cautiously in patients with a history of seizures or with conditions that potentially lower the seizure threshold. 11 ) Potential for Cognitive and Motor Impairment: Has potential to impair judgment, thinking, and motor skills.
Use caution when operating machinery. 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.
14 ) Hyperprolactinemia: May elevate prolactin levels. 15 ) Use in Combination with Fluoxetine, Lithium or Valproate: Also refer to the package inserts for Symbyax, lithium, or valproate. 16 ) Laboratory Tests: Monitor fasting blood glucose and lipid profiles at the beginning of, and periodically during, treatment.
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. 5 ) , and Patient Counseling Information ( 17 )] .
5%, respectively). , 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 )] . 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. 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. ) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system pathology.
The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; 2) intensive symptomatic treatment and medical monitoring; and 3) treatment of any concomitant serious medical problems for which specific treatments are available.
There is no general agreement about specific pharmacological treatment regimens for NMS. If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered.
The patient should be carefully monitored, since recurrences of NMS have been reported [see Patient Counseling Information ( 17 )] . 4 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported with olanzapine exposure.
DRESS may present with a cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and/or pericarditis.
DRESS is sometimes fatal. Discontinue olanzapine if DRESS is suspected [see Patient Counseling Information ( 17 )] . 5 Metabolic Changes Atypical antipsychotic drugs have been associated with metabolic changes including hyperglycemia, dyslipidemia, and weight gain.
Metabolic changes may be associated with increased cardiovascular/cerebrovascular risk. Olanzapine's specific metabolic profile is presented below. Hyperglycemia and Diabetes Mellitus Healthcare providers should consider the risks and benefits when prescribing olanzapine to patients with an established diagnosis of diabetes mellitus, or having borderline increased blood glucose level (fasting 100 mg/dL to 126 mg/dL, nonfasting 140 mg/dL to 200 mg/dL).
Patients taking olanzapine should be monitored regularly for worsening of glucose control. Patients starting treatment with olanzapine should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment.
Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing.
In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the suspect drug [see Patient Counseling Information ( 17 )] .
Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics including olanzapine. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population.
Epidemiological studies suggest an increased risk of treatment-emergent hyperglycemia-related adverse reactions in patients treated with the atypical antipsychotics. While relative risk estimates are inconsistent, the association between atypical antipsychotics and increases in glucose levels appears to fall on a continuum and olanzapine appears to have a greater association than some other atypical antipsychotics.
2 months) with olanzapine in phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). 0 mg/dL. 3 mg/dL. 34 mg/dL. 17 mg/dL). The difference in mean changes between olanzapine and placebo was greater in patients with evidence of glucose dysregulation at baseline (patients diagnosed with diabetes mellitus or related adverse reactions, patients treated with anti-diabetic agents, patients with a baseline random glucose level ≥200 mg/dL, and/or a baseline fasting glucose level ≥126 mg/dL).
06% in placebo-treated subjects (median exposure 17 days). 8% of placebo-treated subjects (N=599). 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 a Not Applicable. 2 mg/dL (N=487). In analyses of patients who completed 9-12 months of olanzapine therapy, mean change in fasting and nonfasting glucose levels continued to increase over time.
Olanzapine Monotherapy in Adolescents — The safety and efficacy of olanzapine have not been established in patients under the age of 13 years. 59 mg/dL). 1 mg/dL (N=121). 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 a Not Applicable. 1% Placebo 13 0% NA a NA a Dyslipidemia Undesirable alterations in lipids have been observed with olanzapine use. Clinical monitoring, including baseline and periodic follow-up lipid evaluations in patients using olanzapine, is recommended [see Patient Counseling Information ( 17 )] .
Clinically significant, and sometimes very high (>500 mg/dL), elevations in triglyceride levels have been observed with olanzapine use. Modest mean increases in total cholesterol have also been seen with olanzapine use. 7 mg/dL for placebo-treated patients.
For fasting HDL cholesterol, no clinically meaningful differences were observed between olanzapine-treated patients and placebo-treated patients. Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were greater in patients without evidence of lipid dysregulation at baseline, where lipid dysregulation was defined as patients diagnosed with dyslipidemia or related adverse reactions, patients treated with lipid lowering agents, or patients with high baseline lipid levels.
16 mg/dL. In an analysis of patients who completed 12 months of therapy, the mean nonfasting total cholesterol did not increase further after approximately 4-6 months. The proportion of patients who had changes (at least once) in total cholesterol, LDL cholesterol or triglycerides from normal or borderline to high, or changes in HDL cholesterol from normal or borderline to low, was greater in long-term studies (at least 48 weeks) as compared with short-term studies.
Table 4 shows categorical changes in fasting lipids values.
Table 4:
Changes in Fasting Lipids Values from Adult Olanzapine Monotherapy Studies a Not Applicable. 5 mg/dL. 4 mg/dL. Olanzapine Monotherapy in Adolescents — The safety and efficacy of olanzapine have not been established in patients under the age of 13 years.
1 mg/dL for placebo-treated adolescents. For fasting HDL cholesterol, no clinically meaningful differences were observed between olanzapine-treated adolescents and placebo-treated adolescents. 5 mg/dL. Table 5 shows categorical changes in fasting lipids values in adolescents.
Table 5:
Changes in Fasting Lipids Values from Adolescent Olanzapine Monotherapy Studies a Not Applicable. 6% Placebo 9 0% NA a NA a Weight Gain Potential consequences of weight gain should be considered prior to starting olanzapine. Patients receiving olanzapine should receive regular monitoring of weight [see Patient Counseling Information ( 17 )] .
3% of placebo-treated patients, with a median exposure to event of 12 weeks. Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) categories. 2% of olanzapine-treated patients and in 0% of placebo-treated patients.
3 lb) (median exposure of 573 days, N=2021). The percentages of patients who gained at least 7%, 15%, or 25% of their baseline body weight with long-term exposure were 64%, 32%, and 12%, respectively. 4% of olanzapine-treated patients following at least 48 weeks of exposure.
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. 2 2 Dose group differences with respect to weight gain have been observed.
3 kg; 40 mg/day: 3 kg) was observed with significant differences between 10 mg/day vs 40 mg/day. Olanzapine Monotherapy in Adolescents — The safety and efficacy of olanzapine have not been established in patients under the age of 13 years.
Mean increase in weight in adolescents was greater than in adults. In 4 placebo-controlled trials, discontinuation due to weight gain occurred in 1% of olanzapine-treated patients, compared to 0% of placebo-treated patients. 6 lb); (median exposure of 201 days, N=179).
The percentages of adolescents who gained at least 7%, 15%, or 25% of their baseline body weight with long-term exposure were 89%, 55%, and 29%, respectively. 9 lb), respectively, for normal (N=106), overweight (N=26) and obese (N=17).
2% of olanzapine-treated patients following at least 24 weeks of exposure. 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. 032 mg per 5 mg, 10 mg, 15 mg, or 20 mg tablet, respectively). 6 Tardive Dyskinesia A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs.
Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome.
Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown. The risk of developing tardive dyskinesia and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase.
However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses or may even arise after discontinuation of treatment. Tardive dyskinesia may remit, partially or completely, if antipsychotic treatment is withdrawn.
Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown.
Given these considerations, olanzapine should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients (1) who suffer from a chronic illness that is known to respond to antipsychotic drugs, and (2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate.
In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically. If signs and symptoms of tardive dyskinesia appear in a patient on olanzapine, drug discontinuation should be considered.
However, some patients may require treatment with olanzapine despite the presence of the syndrome. For specific information about the warnings of lithium or valproate, refer to the Warnings section of the package inserts for these other products.
7 Orthostatic Hypotension Olanzapine may induce orthostatic hypotension associated with dizziness, tachycardia, bradycardia and, in some patients, syncope, especially during the initial dose-titration period, probably reflecting its α 1 -adrenergic antagonistic properties [see Patient Counseling Information ( 17 )] .
From an analysis of the vital sign data in an integrated database of 41 completed clinical studies in adult patients treated with oral olanzapine, orthostatic hypotension was recorded in ≥20% (1277/6030) of patients. For oral olanzapine therapy, the risk of orthostatic hypotension and syncope may be minimized by initiating therapy with 5 mg QD [see Dosage and Administration ( 2 )] .
A more gradual titration to the target dose should be considered if hypotension occurs. 6% (15/2500) of olanzapine-treated patients in phase 2-3 oral olanzapine studies. The risk for this sequence of hypotension, bradycardia, and sinus pause may be greater in nonpsychiatric patients compared to psychiatric patients who are possibly more adapted to certain effects of psychotropic drugs.
Olanzapine should be used with particular caution in patients with known cardiovascular disease (history of myocardial infarction or ischemia, heart failure, or conduction abnormalities), cerebrovascular disease, and conditions which would predispose patients to hypotension (dehydration, hypovolemia, and treatment with antihypertensive medications) where the occurrence of syncope, or hypotension and/or bradycardia might put the patient at increased medical risk.
Caution is necessary in patients who receive treatment with other drugs having effects that can induce hypotension, bradycardia, respiratory or central nervous system depression [see Drug Interactions ( 7 )] . 8 Falls Olanzapine may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries.
For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy. 9 Leukopenia, Neutropenia, and Agranulocytosis Class Effect — In clinical trial and/or postmarketing experience, events of leukopenia/neutropenia have been reported temporally related to antipsychotic agents, including olanzapine.
Agranulocytosis has also been reported. Possible risk factors for leukopenia/neutropenia include pre-existing low white blood cell count (WBC) and history of drug induced leukopenia/neutropenia. Patients with a history of a clinically significant low 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.
Patients with clinically significant neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count <1000/mm 3 ) should discontinue olanzapine and have their WBC followed until recovery.
10 Dysphagia Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Aspiration pneumonia is a common cause of morbidity and mortality in patients with advanced Alzheimer's disease. Olanzapine is not approved for the treatment of patients with Alzheimer's disease.
9% (22/2500) of olanzapine-treated patients. There were confounding factors that may have contributed to the occurrence of seizures in many of these cases. , Alzheimer's dementia. Olanzapine is not approved for the treatment of patients with Alzheimer's disease.
Conditions that lower the seizure threshold may be more prevalent in a population of 65 years or older. 12 Potential for Cognitive and Motor Impairment Somnolence was a commonly reported adverse reaction associated with olanzapine treatment, occurring at an incidence of 26% in olanzapine patients compared to 15% in placebo patients.
This adverse reaction was also dose related. 4% (9/2500) of patients in the premarketing database. Since olanzapine has the potential to impair judgment, thinking, or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that olanzapine therapy does not affect them adversely [see Patient Counseling Information ( 17 )] .
13 Body Temperature Regulation Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic agents. , exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity, or being subject to dehydration [see Patient Counseling Information ( 17 )] .
2 ] . In premarketing clinical trials, Olanzapine was associated with constipation, dry mouth, and tachycardia, all adverse reactions possibly related to cholinergic antagonism. Such adverse reactions were not often the basis for discontinuations, but Olanzapine should be used with caution in patients with a current diagnosis or prior history of urinary retention, clinically significant prostatic hypertrophy, constipation, or a history of paralytic ileus or related conditions.
1 )] . 15 Hyperprolactinemia As with other drugs that antagonize dopamine D 2 receptors, olanzapine elevates prolactin levels, and the elevation persists during chronic administration. Hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion.
This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds.
Long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both female and male subjects. Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent in vitro, a factor of potential importance if the prescription of these drugs is contemplated in a patient with previously detected breast cancer.
1 )] . Neither clinical studies nor epidemiologic studies conducted to date have shown an association between chronic administration of this class of drugs and tumorigenesis in humans; the available evidence is considered too limited to be conclusive at this time.
5% of adults treated with placebo. 2% [9/4896] of males). In placebo-controlled olanzapine monotherapy studies in adolescent patients (up to 6 weeks) with schizophrenia or bipolar I disorder (manic or mixed episodes), changes from normal to high in prolactin concentrations were observed in 47% of olanzapine-treated patients compared to 7% of placebo-treated patients.
4 )] . 1 Based on a search of the following terms: amenorrhea, hypomenorrhea, menstruation delayed, and oligomenorrhea. 2 Based on a search of the following terms: anorgasmia, delayed ejaculation, erectile dysfunction, decreased libido, loss of libido, abnormal orgasm, and sexual dysfunction.
3 Based on a search of the following terms: breast discharge, enlargement or swelling, galactorrhea, gynecomastia, and lactation disorder. Dose group differences with respect to prolactin elevation have been observed. 1%) indicated significant differences between 10 mg/day vs 40 mg/day and 20 mg/day vs 40 mg/day.
16 Use in Combination with Fluoxetine, Lithium, or Valproate When using olanzapine and fluoxetine in combination, the prescriber should also refer to the Warnings and Precautions section of the package insert for Symbyax. When using olanzapine in combination with lithium or valproate, the prescriber should refer to the Warnings and Precautions sections of the package inserts for lithium or valproate [see Drug Interactions ( 7 )] .
5 ) and Patient Counseling Information ( 17 )] .
If a patient develops signs and symptoms indicative of NMS, or presents with unexplained high fever without additional clinical manifestations of NMS, all antipsychotic medicines, including olanzapine must be discontinued. 8). In some cases, a prior increase in body weight has been reported which may be a predisposing factor.
Appropriate clinical monitoring is advisable in accordance with utilised antipsychotic guidelines . g. measuring of blood glucose at baseline, 12 weeks after starting olanzapine treatment and annually thereafter. Patients treated with any antipsychotic medicines, including olanzapine, should be observed for signs and symptoms of hyperglycaemia (such as polydipsia, polyuria, polyphagia, and weakness) and patients with diabetes mellitus or with risk factors for diabetes mellitus should be monitored regularly for worsening of glucose control.
g. at baseline, 4, 8 and 12 weeks after starting olanzapine treatment and quarterly thereafter. 8). Lipid alterations should be managed as clinically appropriate, particularly in dyslipidemic patients and in patients with risk factors for the development of lipids disorders.
g. at baseline, 12 weeks after starting olanzapine treatment and every 5 years thereafter. Anticholinergic activity While olanzapine demonstrated anticholinergic activity in vitro, experience during the clinical trials revealed a low incidence of related events.
However, as clinical experience with olanzapine in patients with concomitant illness is limited, caution is advised when prescribing for patients with prostatic hypertrophy, or paralytic ileus and related conditions. Hepatic function Transient, asymptomatic elevations of hepatic aminotransferases , alanine transferase (ALT), aspartatetransferase (AST) have been seen commonly, especially in early treatment.
Caution should be exercised and follow-up organised in patients with elevated ALT and/or AST, in patients with signs 5 and symptoms of hepatic impairment, in patients with pre-existing conditions associated with limited hepatic functional reserve, and in patients who are being treated with potentially hepatotoxic medicines.
In cases where hepatitis (including hepatocellular, cholestatic or mixed liver […]