Brand names: Lybalvi, ZyPREXA, ZyPREXA IntraMuscular, ZyPREXA Relprevv
Drug class: Atypical Antipsychotics

Medically reviewed by Drugs.com on Aug 10, 2025. Written by ASHP.

Introduction

Thienobenzodiazepine-derivative; atypical antipsychotic agent.

Uses for Olanzapine

Schizophrenia

Used orally (as olanzapine [Zyprexa]) for treatment of schizophrenia in adults and adolescents 13-17 years of age.

In pediatric patients with schizophrenia, symptom profiles can be variable. Initiate medication therapy in pediatric patients only after thorough diagnostic evaluation and careful consideration of risks associated with medication treatment. Drug therapy should be administered as part of a total treatment program that includes psychological, educational, and social interventions.

Used IM (as short-acting olanzapine [Zyprexa IntraMuscular]) for management of acute agitation in adults with schizophrenia.

Used IM (as long-acting olanzapine pamoate [Zyprexa Relprevv] for treatment of schizophrenia in adults.

Used orally (in combination with samidorphan [Lybalvi]) for treatment of schizophrenia in adults.

American Psychiatric Association (APA) and Department of Veterans Affairs/Department of Defense recommend antipsychotic medications for acute and long-term maintenance treatment of schizophrenia. Choice of antipsychotic should be based on patient preference, past response to therapy, concurrent medical conditions, and medication-specific factors (e.g., adverse effect profile, available formulations, potential drug interactions, receptor binding profiles, pharmacokinetic considerations).

American Academy of Child and Adolescent Psychiatry (AACAP) practice parameter recommends antipsychotic medication as a primary treatment for schizophrenia spectrum disorders in children and adolescents. Choice of antipsychotic medication in pediatric patients should be individualized based on FDA-labeling, adverse effect profiles, patient and family preferences, cost, and clinician familiarity.

Bipolar Disorder

Used orally for acute treatment of mixed or manic episodes associated with bipolar I disorder as monotherapy in adults and adolescent patients 13-17 years of age and as adjunctive therapy with lithium or valproate in adults.

Used orally for maintenance treatment of bipolar I disorder in adults and pediatric patients. Pediatric patients with bipolar I disorder may have variable patterns of periodicity of manic or mixed symptoms. Medication therapy for pediatric patients should only be initiated after a thorough diagnostic evaluation and careful consideration of risks associated with medication treatment. Medication treatment for pediatric patients is indicated as part of a total treatment program that often includes psychological, educational, and social interventions.

Used IM (as short-acting olanzapine [Zyprexa IntraMuscular]) for management of acute agitation in adults with bipolar I disorder.

Used orally for treatment (in combination with fluoxetine [Symbyax]) of acute depressive episodes associated with bipolar I disorder. Olanzapine monotherapy is not indicated for treatment of depressive episodes associated with bipolar I disorder.

Used orally (in combination with samidorphan [Lybalvi]) for acute treatment of manic or mixed episodes associated with bipolar I disorder in adults as monotherapy and as an adjunct to lithium or valproate, and for maintenance monotherapy treatment of bipolar I disorder. APA recommends lithium or valproate plus an antipsychotic for first-line treatment of severe manic or mixed episodes; for patients with less severe symptoms, monotherapy with lithium, valproate, or an antipsychotic may be appropriate. Selection of a specific treatment is based on clinical factors (e.g., illness severity, associated features, patient preference, adverse effect profile of the medication). Recommended agents for maintenance treatment include lithium and valproate.

Department of Veterans Affairs/Department of Defense recommends lithium or quetiapine monotherapy for first-line treatment of acute mania associated with bipolar disorder; recommended alternative agents include olanzapine, paliperidone, and risperidone. If none of these agents are suitable based on patient preference or characteristics, other alternatives include aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, valproate, or ziprasidone. In patients with breakthrough episodes or unsatisfactory response to initial treatment, lithium or valproate in combination with an antipsychotic (haloperidol, asenapine, quetiapine, olanzapine, or risperidone) is recommended. Recommended agents for maintenance therapy include lithium and quetiapine; alternatives include olanzapine, paliperidone, or risperidone. May also use aripiprazole, olanzapine, quetiapine, or ziprasidone in combination with lithium or valproate for prevention of mania recurrence.

An AACAP practice parameter recommends pharmacotherapy as primary treatment for mania in bipolar I disorder in children and adolescents. Lithium, valproate, and/or atypical antipsychotic agents are considered standard therapy based on adult literature. Choice of medication in pediatric patients should be based on evidence for efficacy, phase of illness, presence of confounding symptoms, adverse effect profiles, patient history of response to medication, and patient and family preferences.

Treatment-resistant Depression

Used orally for acute and maintenance therapy (in combination with fluoxetine [Symbyax]) of treatment-resistant depression (major depressive disorder in patients who do not respond to 2 separate trials of different antidepressants of adequate dosage and duration in the current episode) in adults.

Not indicated for treatment-resistant depression as monotherapy.

Guidelines from the APA and the Department of Veterans Affairs/Department of Defense state that there is no evidence to suggest superiority of one first-line antidepressant over another. Recommended first-line agents for initial treatment of major depressive disorder include bupropion, mirtazapine, a selective serotonin-reuptake inhibitor (SSRI), a serotonin-norepinephrine reuptake inhibitor (SNRI), trazodone, vilazodone, or vortioxetine. For patients who do not respond or have an inadequate response to initial treatment with an antidepressant, options include changing to a different antidepressant or psychotherapy, or augmentation with psychotherapy or another pharmacological agent.

Cancer Chemotherapy-induced Nausea and Vomiting

Has been used orally (in combination with other antiemetic agents) forprevention of acute and delayed nausea and vomiting associated with highly emetogenic cancer chemotherapy^{† [off-label]}, including high-dose cisplatin therapy.

Olanzapine also has been shown to be an effective rescue antiemetic in patients who develop breakthrough chemotherapy-induced nausea and vomiting^{† [off-label]} despite optimal antiemetic prophylaxis.

For prevention of nausea and vomiting associated with highly emetogenicchemotherapy regimens (including an anthracycline plus cyclophosphamide), ASCO recommends a 4-drug antiemetic regimen consisting of an NK₁ receptor antagonist (e.g., aprepitant, fosaprepitant, netupitant [in fixed combination with palonosetron], fosnetupitant [in fixed combination with palonosetron], rolapitant), a 5-HT₃ receptor antagonist (e.g., dolasetron, granisetron, ondansetron, palonosetron), dexamethasone, and olanzapine.

ASCO does not recommend olanzapine in such patients. For adults receiving carboplatin with a target AUC of ≥4 mg/mL per minute, ASCO recommends a 3-drug antiemetic regimen consisting of an NK₁ receptor antagonist, a 5-HT₃ receptor antagonist, and dexamethasone. For adults receiving other chemotherapy of moderate emetic risk, excluding carboplatin with a target AUC of ≥4 mg/mL per minute, ASCO recommends a 2-drug antiemetic regimen consisting of a 5-HT₃ receptor antagonist and dexamethasone.

For chemotherapy regimens with low emetic risk, ASCO recommends a single dose of either a 5-HT₃ receptor antagonist or dexamethasone alone on the first day of chemotherapy.

For chemotherapy regimens with minimal emetic risk, ASCO states that routine antiemetic prophylaxis is not necessary.

For adults treated with high-dose chemotherapy and stem-cell or bone marrow transplantation, ASCO recommends a 3-drug antiemetic regimen, consisting of an NK₁ receptor antagonist, a 5-HT₃ receptor antagonist, and dexamethasone, be offered. A 4-drug combination antiemetic regimen that includes olanzapine may also be offered.

For patients with breakthrough chemotherapy-induced nausea or vomiting, ASCO recommends clinicians reevaluate emetic risk, disease status, and concomitant medical conditions and medications and determine whether the best antiemetic regimen is being provided for the emetic risk. In adults who experience nausea and vomiting despite optimal antiemetic prophylaxis and who have not received olanzapine prophylactically, ASCO states that olanzapine may be added to the standard antiemetic regimen. In adults who experience nausea or vomiting despite optimal antiemetic prophylaxis and who have already received olanzapine, may add an antiemetic drug from a different class (i.e., an NK₁ receptor antagonist, lorazepam or alprazolam, a dopamine receptor antagonist, dronabinol, or nabilone) to the standard antiemetic regimen.

Cancer Cachexia

Used for management of cancer cachexia in adults with advanced cancer^{† [off-label]} .

A rapid guideline update from ASCO states that for adults with advanced cancer, clinicians may offer low-dose olanzapine daily to improve weight gain and appetite.

Behavioral and Psychological Symptoms with Dementia

Has been used by IM injection for management of behavioral and psychological symptoms associated with dementia^{† [off-label]}.

APA recommends that antipsychotic medication should only be used for the treatment of agitation or psychosis in patients with dementia when symptoms are severe, are dangerous, and/or cause significant distress to the patient. In another treatment algorithm, for the diagnosis of emergent BPSD associated with dementia, first-line pharmacotherapy is olanzapine IM. If there is an inadequate or no response, haloperidol IM, followed by benzodiazepines IM, are recommended.

American Geriatrics Society (AGS) 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults state that antipsychotics should be avoided in patients with cognitive impairment or dementia due to increased risk of stroke and greater rate of cognitive decline and mortality. Antipsychotics should be avoided unless documented nonpharmacologic options have failed and/or the patient is threatening substantial harm to self and others; if used, use the lowest effective dose and consider periodic deprescribing attempts.

Generalized Anxiety Disorder

Used for the management of refractory generalized anxiety disorder in adults^{† [off-label]} .

International experts state that olanzapine, as an add-on therapy with fluoxetine, may be used for treatment-refractory generalized anxiety disorder.

Obsessive-Compulsive Disorder

Used for the management of obsessive-compulsive disorder (OCD) in adults^† .

Legacy guideline from APA lists SSRIs (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline) as first-line pharmacotherapy for OCD. If a patient does not respond to one SSRI, they may switch to a different SSRI, clomipramine, venlafaxine, or mirtazapine, or augment their current SSRI with a second-generation antipsychotic.

Posttraumatic Stress Disorder

Used for the management of refractory posttraumatic stress disorder (PTSD) in adults^†.

International experts state that olanzapine, as monotherapy or as an add-on to SSRIs, is effective in treatment-unresponsive PTSD, but should only be used when standard treatments have failed or have not been tolerated due to a higher rate of adverse effects. Department of Veterans Affairs and Department of Defense guidelines state there is insufficient evidence to recommend for or against use of olanzapine for the treatment of PTSD and suggest against olanzapine as augmentation for the treatment of PTSD.

Olanzapine Dosage and Administration

General

Pretreatment Screening

• Monitor fasting blood glucose and lipids at baseline prior to initiating treatment with olanzapine.

• Complete a fall risk assessment when initiating olanzapine in patients with concomitant diseases, conditions, or medications that could exacerbate the risk of falls.

Patient Monitoring

• Monitor patients for hyperglycemia/diabetes mellitus, dyslipidemia, and weight gain. Periodically monitor fasting blood glucose, lipids, and weight during treatment. Regularly monitor patients for worsening of glucose control.

• Monitor for the emergence of neuroleptic malignant syndrome (NMS).

• In patients with a pre-existing low WBC or a history of drug-induced leukopenia/neutropenia, monitor CBC frequently during the first few months of therapy. In patients with neutropenia, monitor for fever or other symptoms or signs of infection; treat promptly if such symptoms or signs occur.

• For patients with diseases, conditions, or medications that could exacerbate the risk of falls, complete fall risk assessments periodically during long-term olanzapine therapy.

• Monitor for suicidal behavior in high-risk patients during olanzapine therapy.

Dispensing and Administration Precautions

• According to the Institute for Safe Medication Practices (ISMP), brand and generic names for olanzapine-containing products may be confused with brand and/or generic names of other products. ISMP recommends strategies such as using both brand and generic names on prescription labels, including the purpose of the medication on prescriptions, configuring computer systems to require a minimum of the first 5 letters of a drug name during product searches, and changing the appearance of look-alike product names to draw attention to their differences to help mitigate these risks.

• The 2023 American Geriatrics Society (AGS) Beers Criteria for Potentially Inappropriate Medication (PIM) Use in Older Adults includes olanzapine on the list of PIMs that are best avoided by older adults in most circumstances or under specific situations, such as certain diseases, conditions, or care settings. The criteria are intended to apply to adults 65 years of age and older in all ambulatory, acute, and institutional settings of care, except hospice and end-of-life care settings. The Beers Criteria Expert Panel recommends that use of antipsychotics such as olanzapine be avoided in such patients except in FDA-approved indications such as schizophrenia, bipolar disorder, Parkinson disease psychosis, adjunctive treatment of major depressive disorder, or for short-term use as an antiemetic.

REMS

• Because of the risk of post-injection delirium/sedation syndrome (PDSS), extended-release olanzapine pamoate injection is available only under a restricted distribution program, the Zyprexa Relprevv Patient Care Program.

• Zyprexa Relprevv must not be dispensed directly to a patient. For a patient to receive treatment, the prescriber, healthcare facility, patient, and pharmacy must all be enrolled in the Patient Care Program.

• Clinicians may contact 877-772-9390 for additional information and to enroll in the Zyprexa Relprevv Patient Care Program or consult the manufacturer’s website ([Web]).

Other General Considerations

• Individuals with phenylketonuria (i.e., homozygous genetic deficiency of phenylalanine hydroxylase) and other individuals who must restrict their intake of phenylalanine should be warned that olanzapine orally disintegrating tablets contain aspartame, which is metabolized in the GI tract to provide phenylalanine following oral administration; the respective manufacturer’s labeling should be consulted for specific information regarding phenylalanine content of individual preparations and dosage strengths.

Administration

Administer olanzapine orally or by IM injection. Administer olanzapine pamoate only by IM injection. Oral olanzapine also available in fixed combination with fluoxetine or samidorphan; refer to prescribing information for olanzapine/samidorphan (Lybalvi) for specific information on administration and dosing.

Establish tolerability with oral olanzapine prior to initiating extended-release olanzapine pamoate IM therapy.

Oral Administration

Administer olanzapine orally as conventional tablets or orally disintegrating tablets. Also available as fixed-combination tablets with samidorphan and fixed-combination capsules with fluoxetine, both of which are administered orally. Administer oral olanzapine formulations once daily without regard to meals. Administer fixed-combination olanzapine and fluoxetine capsules (e.g., Symbyax) in the evening.

Just prior to administration of orally disintegrating tablets, gently remove tablet from blister packet; do not push tablet through foil. With dry hands, peel open blister package, place tablet on tongue to dissolve, and swallow with or without liquid.

IM Administration of Short-acting Olanzapine (e.g., Zyprexa IntraMuscular)

Short-acting (immediate-release) olanzapine (10 mg per vial) is used for agitation associated with schizophrenia or bipolar mania; do not confuse this formulation with the long-acting olanzapine pamoate formulation (Zyprexa Relprevv; available in 210-, 300-, and 405-mg vial strengths) used for schizophrenia.

Administer only by IM injection; inject drug slowly and deeply into the muscle mass. Do not administer IV or sub-Q.

Reconstitution

Reconstitute short-acting olanzapine for injection by adding 2.1 mL of sterile water for injection to vial containing 10 mg of olanzapine to provide a solution containing approximately 5 mg/mL. Do not use other solutions to reconstitute olanzapine for injection.

Use immediately (within 1 hour) following reconstitution. If necessary, the reconstituted solution may be stored for up to 1 hour at 20–25°C; after 1 hour, discard any unused portion.

IM Administration of Long-acting Olanzapine Pamoate (Zyprexa Relprevv)

Long-acting olanzapine pamoate (available in 210-, 300-, and 405-mg vial strengths) is used for schizophrenia; do not confuse this formulation with the short-acting (immediate-release) olanzapine formulation (e.g., Zyprexa IntraMuscular; 10 mg per vial) used for agitation associated with schizophrenia or bipolar mania.

Administer only by deep IM injection into the gluteal area; do not administer IV or sub-Q. A healthcare professional should administer the injection every 2–4 weeks.

Following insertion of the needle into the gluteal muscle for the IM injection, aspirate for several seconds to ensure that no blood is drawn into the syringe. If blood appears in the syringe, withdraw the needle and discard the syringe and dose. Use a new convenience kit for the new dose with a new syringe and needle. Do not massage injection site following IM administration.

Reconstitution

Consult manufacturer’s labeling for instructions for using components of the Zyprexa Relprevv Convenience Kit for reconstitution of olanzapine pamoate powder for suspension. Reconstitute only with diluent supplied by manufacturer.

Reconstituted olanzapine pamoate suspension remains stable for up to 24 hours in the vial. If not used immediately, shake the vial vigorously to resuspend the drug prior to administration.

Dosage

Available as olanzapine and olanzapine pamoate; dosage expressed in terms of olanzapine.

For treatment of psychiatric indications (e.g., psychotic disorders, bipolar disorder, treatment-resistant depression), adjust olanzapine dosage carefully according to individual requirements and response, using the lowest possible effective dosage.

Pediatric Patients

Schizophrenia

Oral

Adolescents 13–17 years of age: Initially, 2.5 or 5 mg once daily. May increase to a target dosage of 10 mg daily.

Make subsequent dosage adjustments in increments or decrements of 2.5 or 5 mg daily.

Effective dosage in clinical studies generally ranged from 2.5–20 mg daily (mean dosage of about 11 mg daily).

Optimum duration of therapy not known, but maintenance therapy with olanzapine is well established in adults. In responsive patients, continue the drug beyond the acute response at the lowest effective dosage; periodically reassess need for continued maintenance therapy.

Bipolar Disorder

Manic or Mixed Episodes: Monotherapy

Oral

Adolescents 13–17 years of age: Initially, 2.5 or 5 mg once daily. May increase to a target dosage of 10 mg daily.

Make subsequent dosage adjustments in increments or decrements of 2.5 or 5 mg daily.

Effective dosage in clinical studies generally ranged from 2.5–20 mg daily (mean dosage of about 9 mg daily).

Optimum duration of therapy not known, but maintenance therapy with olanzapine is well established in adults. In responsive patients, continue the drug beyond the acute response at the lowest effective dosage; periodically reassess need for continued maintenance therapy.

Acute Depressive Episodes

Oral

Children and adolescents 10–17 years of age: Initially 2.5 mg in combination with 20 mg of fluoxetine, or 3 mg in fixed combination with 25 mg of fluoxetine (e.g., Symbyax) once daily in the evening.

Increase dosage according to patient response and tolerance as indicated to a target dosage of olanzapine 6–12 mg with fluoxetine 25–50 mg daily.

If elect to use combined olanzapine and fluoxetine therapy for extended periods, periodically reevaluate the long-term risks and benefits for the individual patient.

Adults

Schizophrenia

Oral

Initially, 5–10 mg, usually as a single daily dose. May increase by 5 mg daily up to a target dosage of 10 mg daily within several days.

Make subsequent dosage adjustments at intervals of not less than 7 days, usually in increments or decrements of 5 mg once daily.

Increasing dosage beyond 10 mg daily usually does not result in greater efficacy; such increases generally should occur only after assessment of the patient’s clinical status.

Optimum duration of therapy currently is not known, but maintenance therapy with antipsychotic agents is well established. In responsive patients, continue as long as clinically necessary and tolerated, but at lowest possible effective dosage; reassess need for continued therapy periodically.

IM, Extended-release Olanzapine Pamoate

Establish tolerability with oral olanzapine prior to initiating extended-release olanzapine pamoate IM (Zyprexa Relprevv) therapy.

For patients established on oral olanzapine 10 mg daily, recommended initial dosage is 210 mg every 2 weeks or 405 mg every 4 weeks for first 8 weeks. After 8 weeks, recommended maintenance dosage is 150 mg every 2 weeks or 300 mg every 4 weeks.

For patients established on oral olanzapine 15 mg daily, recommended initial dosage is 300 mg every 2 weeks for first 8 weeks. After 8 weeks, recommended maintenance dosage is 210 mg every 2 weeks or 405 mg every 4 weeks.

For patients established on oral olanzapine 20 mg daily, recommended initial and maintenance dosage is 300 mg every 2 weeks.

Efficacy demonstrated in clinical studies within dosage range of 150–300 mg administered every 2 weeks and with 405 mg administered every 4 weeks.

A lower initial dosage of 150 mg every 4 weeks recommended in patients who are debilitated, who may be predisposed to hypotensive reactions, who exhibit a combination of factors that may result in slower metabolism of olanzapine (e.g., nonsmoking female patients ≥65 years), or who may be more sensitive to the pharmacodynamic effects of the drug. When indicated, escalate dosage with caution in such patients.

Optimum duration of therapy not known, but long-term efficacy demonstrated over a 24-week period. In addition, long-term use of oral olanzapine has been shown to maintain treatment response in patients with schizophrenia. If used for an extended period, periodically reassess need for continued maintenance therapy.

Acute Agitation associated with Schizophrenia

IM, Short-acting Olanzapine

Initially, 10 mg of short-acting olanzapine (e.g., Zyprexa IntraMuscular). Consider lower doses (2.5, 5, or 7.5 mg) when clinically warranted.

In clinical trials, efficacy in controlling agitation in patients with schizophrenia or bipolar mania demonstrated in a dosage range of 2.5–10 mg.

If agitation persists, may administer subsequent single doses of up to 10 mg. However, efficacy of repeated doses was not systematically evaluated in controlled trials.

Assess patients for orthostatic hypotension prior to administration of any subsequent IM doses.

If ongoing therapy is indicated, may initiate oral olanzapine 5–20 mg daily as soon as clinically appropriate.

Bipolar Disorder

Manic or Mixed Episodes: Monotherapy

Oral

Initially, usually 10 or 15 mg once daily. Make dosage adjustments in increments or decrements of 5 mg daily, at intervals of not less than 24 hours.

Effective dosage in clinical studies generally ranged from 5–20 mg daily.

If elect to use olanzapine for extended periods, periodically reevaluate the long-term usefulness for the individual patient.

Manic or Mixed Episodes: Combination Therapy

Oral

Initially, 10 mg once daily when administered with lithium or valproate.

Effective dosage of olanzapine in clinical studies generally ranged from 5–20 mg daily.

No dosage adjustment of lithium or valproate is required when used in combination with olanzapine.

If elect to use olanzapine for extended periods, periodically reevaluate the long-term usefulness for the individual patient.

Acute Depressive Episodes

Oral

Initially, 5 mg in combination with 20 mg of fluoxetine, or 6 mg in fixed combination with 25 mg of fluoxetine (e.g., Symbyax) once daily in the evening.

Increase dosage according to patient response and tolerance.

In clinical trials, antidepressive efficacy was demonstrated at olanzapine dosages ranging from 6–12 mg daily and fluoxetine dosages ranging from 25–50 mg daily.

If combination therapy with olanzapine and fluoxetine is used for extended periods, periodically reevaluate the long-term risks and benefits for the individual patient.

Acute Agitation associated with Bipolar Mania

IM, Short-acting Olanzapine

Initially, 10 mg of short-acting olanzapine (e.g., Zyprexa IntraMuscular). Consider lower doses (2.5, 5, or 7.5 mg) when clinically warranted.

In clinical trials, efficacy in controlling agitation in patients with schizophrenia or bipolar mania demonstrated in a dosage range of 2.5–10 mg.

If agitation persists, may administer subsequent single doses of up to 10 mg. However, efficacy of repeated doses was not systematically evaluated in controlled trials.

Assess patients for orthostatic hypotension prior to administration of any subsequent IM doses.

If ongoing therapy is indicated, may initiate oral olanzapine 5–20 mg daily as soon as clinically appropriate.

Treatment-resistant Depression

Oral

Initially, 5 mg in combination with 20 mg of fluoxetine, or 6 mg in fixed combination with 25 mg of fluoxetine (e.g., Symbyax) once daily in the evening.

Increase dosage according to patient response and tolerance as indicated to a target dosage of olanzapine 5–20 mg with fluoxetine 20–50 mg daily.

In clinical trials, antidepressive efficacy was demonstrated at olanzapine dosages ranging from 6–18 mg daily and fluoxetine dosages ranging from 25–50 mg daily.

Optimum duration of therapy not known; periodically reassess need for continued maintenance therapy.

Chemotherapy-induced Nausea and Vomiting

Highly Emetogenic Cancer Chemotherapy

Oral

For the prevention of acute and delayed nausea and vomiting^†, usually has been administered as part of a regimen that includes an NK₁ receptor antagonist, a 5-HT₃ receptor antagonist, and dexamethasone.

Administer 5–10 mg once daily before chemotherapy on day 1 followed by 510 mg once daily on days 2–4 of chemotherapy.

Breakthrough Nausea and Vomiting associated with Cancer Chemotherapy

Oral

For the treatment of breakthrough nausea and vomiting^† despite optimal antiemetic prophylaxis, olanzapine 10 mg once daily has been given for 3 days in a controlled clinical study.

Cancer Cachexia

Oral

For the management of cachexia in adults with advanced cancer^†, a dose of 2.5 mg once daily is recommended to improve weight gain and appetite. This recommendation is based on a study where patients received olanzapine 2.5 mg once daily for 12 weeks.

Special Populations

Hepatic Impairment

When olanzapine is used in combination with fluoxetine in patients with hepatic impairment, an initial dose of oral olanzapine 2.5–5 mg and fluoxetine 20 mg is recommended.

Extended-release IM formulation (Zyprexa Relprevv) not specifically studied in hepatic impairment.

Renal Impairment

Dosage adjustment not necessary.

Extended-release IM formulation (Zyprexa Relprevv) not specifically studied in renal impairment.

Geriatric Patients

Consider a lower initial dosage of oral olanzapine and extended-release IM olanzapine pamoate (Zyprexa Relprevv) in geriatric patients.

Consider a lower initial IM dose of 5 mg of short-acting olanzapine.

Cautions for Olanzapine

Contraindications

• None.

Warnings/Precautions

Warnings

Increased Mortality in Geriatric Patients with Dementia-related Psychosis

Increased risk of death with use of either conventional (first-generation) or atypical (second-generation) antipsychotics in geriatric patients with dementia-related psychosis. (See Boxed Warning.)

Antipsychotic agents, including olanzapine, are not approved for the treatment of dementia-related psychosis.

Post-injection Delirium/Sedation Syndrome (PDSS) with Extended-release Injection

Manifestations consistent with olanzapine overdosage, particularly sedation and/or delirium, reported following extended-release olanzapine pamoate (Zyprexa Relprevv) injection. (See Boxed Warning.) In some cases, events correlated with a rapid, greater than expected increase in serum olanzapine concentrations to supratherapeutic ranges, but mechanism by which the drug entered bloodstream is not known.

Manifestations of PDSS include dizziness, confusion, disorientation, slurred speech, altered gait, ambulation difficulties, weakness, agitation, extrapyramidal symptoms, hypertension, convulsions, and reduced levels of consciousness (mild sedation to coma). Onset ranges from soon after injection to >3 hours after injection; recovery generally observed by 72 hours.

Risk is cumulative (i.e., increases with the number of injections).

Because of risk of PDSS, Zyprexa Relprevv must be administered in a registered healthcare facility with ready access to emergency response services. (See REMS.) Medication guide should be provided prior to each injection.

Monitor patients at healthcare facility for ≥3 hours following each injection. Patient should be alert, oriented, and absent of signs of PDSS before being released, and must be accompanied to their destination upon leaving. Patients should not drive or operate heavy machinery for the rest of the day after injection, and should continue to monitor for signs of PDSS.

Other Warnings and Precautions

Suicide

Attendant risk with psychotic illness and bipolar disorder; closely supervise high-risk patients.

Prescribe in the smallest quantity consistent with good patient management to reduce the risk of overdosage.

Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome characterized by hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability, reported with antipsychotic agents, including olanzapine.

Immediately discontinue therapy and initiate supportive and symptomatic therapy if NMS occurs. Careful monitoring recommended if therapy is reinstituted following recovery; the risk that NMS can recur must be considered.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

DRESS, which is sometimes fatal, reported with olanzapine. Clinical presentation includes cutaneous reaction (e.g., rash, exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications (e.g., hepatitis, nephritis, pneumonitis, myocarditis, and/or pericarditis).

If DRESS is suspected, discontinue treatment with olanzapine.

Hyperglycemia and Diabetes Mellitus

Hyperglycemia, sometimes severe and associated with ketoacidosis, hyperosmolar coma, or death, reported in patients receiving atypical antipsychotic agents, including olanzapine.

Closely monitor patients with diabetes mellitus for worsening glycemic control and perform fasting glucose testing at baseline and periodically during treatment. If manifestations of hyperglycemia occur, perform fasting blood glucose testing.

Some patients who developed hyperglycemia while receiving an atypical antipsychotic have required continuance of antidiabetic treatment despite discontinuance of the suspect drug; in other patients, hyperglycemia resolved with discontinuance of the antipsychotic.

Dyslipidemia

Undesirable changes in lipid parameters observed with olanzapine use. Clinically important, and sometimes very high (>500 mg/dL), elevations in triglyceride concentrations possible. Modest average increases in total cholesterol concentrations also have occurred.

Manufacturers recommend appropriate clinical monitoring, including baseline and periodic follow-up lipid evaluations.

Weight Gain

Weight gain reported. In placebo-controlled trials, approximately 22% of adults and 41% of adolescent patients receiving olanzapine monotherapy gained ≥7% of their baseline body weight.

Consider potential consequences of weight gain prior to starting olanzapine therapy. Regularly monitor patient weight during therapy.

Tardive Dyskinesia

Tardive dyskinesia, a syndrome of potentially irreversible, involuntary dyskinetic movements, may occur in patients receiving antipsychotic agents.

Reserve long-term antipsychotic treatment for patients with chronic illness known to respond to antipsychotic agents, and for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients requiring chronic treatment, use smallest dosage and shortest duration of treatment producing a satisfactory clinical response; periodically reassess need for continued therapy.

Consider discontinuance of olanzapine if signs and symptoms of tardive dyskinesia occur. However, some patients may require treatment despite the presence of the syndrome.

Orthostatic Hypotension

Risk of orthostatic hypotension associated with dizziness, tachycardia, bradycardia, and syncope, particularly early in treatment, because of olanzapine’s α₁-adrenergic blocking activity. Syncope reported in 0.6, 0.3, and 0.1% of patients receiving oral olanzapine, immediate-release IM olanzapine, and extended-release IM olanzapine pamoate, respectively, in clinical studies. May reduce risk of orthostatic hypotension and syncope by initiating oral therapy at a dosage of 5 mg once daily; if hypotension occurs, consider more gradual titration to target dosage.

Hypotension, bradycardia with or without hypotension, tachycardia, and syncope reported with immediate-release IM olanzapine injection.

Use oral or IM olanzapine with particular caution in patients with known cardiovascular disease (e.g., heart failure, history of MI, ischemic heart disease, conduction abnormalities), cerebrovascular disease, and/or conditions that would predispose patients to hypotension (e.g., dehydration, hypovolemia, concomitant antihypertensive therapy).

Risk of clinically important orthostatic hypotension associated with use of maximum recommended IM dosages of immediate-release olanzapine injection (i.e., three 10-mg IM doses given 2–4 hours apart). If drowsiness or dizziness occurs, patients should remain recumbent until examination indicates that they are not experiencing orthostatic hypotension, bradycardia, and/or hypoventilation. Assess patients for orthostatic hypotension prior to administration of any subsequent IM doses. Administration of additional IM doses to patients with clinically significant postural change in BP is not recommended.

Use oral or IM olanzapine with caution in patients receiving other drugs that can induce hypotension, bradycardia, or respiratory and CNS depression (e.g., benzodiazepines). Avoid concomitant use of immediate-release IM olanzapine injection and parenteral benzodiazepines due to risk of excessive sedation and cardiorespiratory depression.

Falls

May cause somnolence, postural hypotension, and motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries.

In patients with diseases, conditions, or other drugs that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic therapy and repeat such testing periodically during long-term therapy.

Leukopenia, Neutropenia, and Agranulocytosis

Leukopenia and neutropenia temporally related to antipsychotic agents, including olanzapine, reported during clinical trial and/or postmarketing experience. Agranulocytosis also reported.

Possible risk factors for leukopenia and neutropenia include preexisting low WBC count and a history of drug-induced leukopenia or neutropenia. Monitor CBC frequently during the first few months of therapy in patients with such risk factors. Discontinue olanzapine at the first sign of a decline in WBC count in the absence of other causative factors.

Carefully monitor patients with clinically important neutropenia for signs and symptoms of infection (e.g., fever) and treat promptly if they occur. Discontinue olanzapine if severe neutropenia (ANC <1000/mm³) occurs; monitor WBC until recovery occurs.

Dysphagia

Esophageal dysmotility and aspiration associated with the use of antipsychotic agents. Aspiration pneumonia is a common cause of morbidity and mortality in geriatric patients, particularly in those with advanced Alzheimer’s dementia.

Seizures

Seizures reported in 0.9 and 0.15% of adults receiving oral olanzapine or extended-release IM olanzapine pamoate, respectively.

Use with caution in patients with a history of seizures or conditions known to lower the seizure threshold (e.g., dementia of the Alzheimer’s type); conditions that lower seizure threshold may be more prevalent in patients ≥65 years of age.

Cognitive and Motor Impairment

Dose-related somnolence commonly occurs with olanzapine (26% of patients). Sedation occurred in 8% of patients receiving extended-release IM olanzapine pamoate.

Judgment, thinking, or motor skills may be impaired.

Body Temperature Regulation

Disruption of the body’s ability to reduce core body temperature possible with antipsychotic agents.

Use appropriate caution in patients who will be experiencing conditions that may contribute to an elevation in core body temperature (e.g., strenuous exercise, extreme heat, concomitant use of agents with anticholinergic activity, dehydration).

Anticholinergic (Antimuscarinic) Effects

Has demonstrated anticholinergic activity in vitro and anticholinergic adverse effects (e.g., constipation, dry mouth, tachycardia) have been reported in premarketing trials. Use with caution in patients with a current or prior history of urinary retention, clinically important prostatic hypertrophy, constipation, or history of paralytic ileus or related conditions. In postmarketing experience, the risk of severe adverse reactions, including fatalities, was increased with concomitant use of anticholinergic medications.

Hyperprolactinemia

May cause elevated serum prolactin concentrations, which may persist during chronic administration and cause clinical disturbances (e.g., galactorrhea, amenorrhea, gynecomastia, impotence); chronic hyperprolactinemia associated with hypogonadism may lead to decreased bone density.

If contemplating olanzapine therapy in a patient with previously detected breast cancer, consider that approximately one-third of human breast cancers are prolactin dependent in vitro. However, published epidemiologic studies have shown inconsistent results about the potential association between hyperprolactinemia and breast cancer.

Use in Combination with Other Agents

Consider cautions, precautions, and contraindications associated with lithium, valproate, fluoxetine, or samidorphan when olanzapine is used in conjunction with these drugs.

Specific Populations

Pregnancy

National Pregnancy Registry for Atypical Antipsychotics available (for women exposed to olanzapine during pregnancy); to enroll, call 866-961-2388 or visit online at [Web].

Available data from studies of pregnant women exposed to olanzapine have not established drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. However, there are risks to the mother (e.g., risk of relapse, hospitalization, suicide) associated with untreated schizophrenia or bipolar I disorder and with exposure to antipsychotics during pregnancy. Schizophrenia and bipolar I disorder associated with increased adverse perinatal outcomes, including preterm birth.

Developmental toxicity demonstrated in animal studies.

Risk for extrapyramidal and/or withdrawal symptoms (e.g., agitation, hypertonia, hypotonia, tardive dyskinetic-like symptoms, tremor, somnolence, respiratory distress, feeding disorder) in neonates exposed to antipsychotic agents during the third trimester; monitor neonates exhibiting such symptoms and manage appropriately.

Lactation

Distributed into milk. Excess sedation, irritability, poor feeding, and extrapyramidal symptoms (tremors and abnormal muscle movements) reported in infants exposed to olanzapine through breast milk. No data on effects on milk production.

Consider developmental and health benefits of breast-feeding along with the mother’s clinical need for olanzapine and any potential adverse effects on breast-fed child from drug or from mother’s underlying condition.

Monitor infants exposed to olanzapine for excess sedation, irritability, poor feeding, and extrapyramidal symptoms (tremors and abnormal muscle movements).

Females and Males of Reproductive Potential

Possible increase in serum prolactin levels, which may lead to a reversible reduction in fertility in females of reproductive potential.

Pediatric Use

Safety and efficacy of oral olanzapine for the treatment of schizophrenia or manic or mixed episodes associated with bipolar I disorder established in short-term clinical trials in adolescents (13–17 years of age). The recommended initial dosage for adolescents is lower than that for adults. Safety and efficacy of oral olanzapine for the treatment of schizophrenia or manic or mixed episodes associated with bipolar I disorder not established in pediatric patients <13 years of age. Compared with adults in clinical trials, adolescents were likely to gain more weight, experience increased sedation, and have greater increases in serum concentrations of total cholesterol, triglycerides, LDL-cholesterol, prolactin, and hepatic aminotransferases.

Clinicians should consider the potential long-term risks (e.g., weight gain, dyslipidemia) when prescribing olanzapine to adolescents; in many cases, this may lead to consideration of other drugs first in such patients.

Safety and efficacy of oral olanzapine in combination with fluoxetine for the treatment of acute depressive episodes associated with bipolar disorder not established in pediatric patients <10 years of age.

Safety and efficacy of oral olanzapine in combination with fluoxetine for the treatment of treatment-resistant depression not established in patients <18 years of age.

Safety and efficacy of extended-release IM olanzapine pamoate not established in patients <18 years of age.

Geriatric Use

Safety of oral olanzapine in patients ≥65 years of age with schizophrenia does not appear to differ from that in younger adults with schizophrenia; however, tolerability profile of olanzapine in geriatric patients with dementia-related psychosis may differ from that in younger patients with schizophrenia.

The manufacturer states that the presence of factors that might decrease the clearance of or increase the pharmacodynamic response to olanzapine should lead to consideration of a lower initial dosage in geriatric patients.

Geriatric patients with dementia-related psychosis treated with antipsychotic agents, including olanzapine, are at an increased risk of death; increased incidence of adverse cerebrovascular events also observed in geriatric patients with dementia-related psychosis receiving oral olanzapine. Olanzapine is not approved for the treatment of patients with dementia-related psychosis.

Clinical studies of olanzapine in combination with fluoxetine did not include sufficient numbers of patients ≥65 years of age to determine whether they respond differently than younger patients.

Clinical studies of extended-release IM olanzapine pamoate did not include sufficient numbers of patients ≥65 years of age to determine whether they respond differently than younger patients.

Hepatic Impairment

Although presence of hepatic impairment expected to reduce olanzapine clearance, one study of 6 patients with impaired hepatic function and clinically significant cirrhosis revealed little effect on olanzapine pharmacokinetics.

Extended-release IM olanzapine pamoate (Zyprexa Relprevv) not specifically studied in hepatic impairment.

Renal Impairment

Olanzapine is highly metabolized and only minimal amounts (about 7%) are excreted in urine unchanged; renal dysfunction alone unlikely to have a major impact on the pharmacokinetics of olanzapine. Olanzapine pharmacokinetics similar in patients with severe renal impairment and normal subjects, indicating that dosage adjustment is not required in renal impairment. Olanzapine is not removed by dialysis. The effect of renal impairment on metabolite elimination has not been studied.

Extended-release IM olanzapine pamoate (Zyprexa Relprevv) not specifically studied in renal impairment.

Common Adverse Effects

Oral olanzapine monotherapy in adults with schizophrenia: Postural hypotension, constipation, weight gain, dizziness, personality disorder, akathisia.

Oral olanzapine monotherapy in adolescents with schizophrenia: Sedation, weight gain, headache, increased appetite, dizziness, abdominal pain, pain in the extremities, fatigue, dry mouth.

Oral olanzapine therapy for manic or mixed episodes associated with bipolar disorder (as monotherapy) in adults: Asthenia, dry mouth, constipation, increased appetite, somnolence, dizziness, tremor.

Oral olanzapine therapy for manic or mixed episodes associated with bipolar disorder (as monotherapy) in adolescents: Sedation, weight gain, increased appetite, headache, fatigue, dizziness, dry mouth, abdominal pain, pain in the extremities.

Oral olanzapine therapy for manic or mixed episodes associated with bipolar disorder (as adjunctive therapy with lithium or valproate) in adults: Dry mouth, weight gain, increased appetite, dizziness, back pain, constipation, speech disorder, increased salivation, amnesia, paresthesia.

Olanzapine IM (short-acting injection) for agitation associated with schizophrenia or bipolar mania in adults: Somnolence.

Olanzapine pamoate IM (long-acting) therapy in adults: Headache, sedation, weight gain, cough, diarrhea, back pain, nausea, somnolence, dry mouth, nasopharyngitis, increased appetite, vomiting.

Drug Interactions

Direct glucuronidation and CYP-mediated oxidation are main metabolic pathways. In vitro studies suggest that CYP1A2 and CYP2D6 and the flavin-containing monooxygenase system are involved in oxidation; however, CYP2D6-mediated oxidation appears to be a minor pathway.

Appears to have little potential to inhibit CYP isoenzymes 1A2, 2C9, 2C19, 2D6, and 3A.

Although metabolized by multiple enzyme systems, induction or inhibition of a single enzyme may appreciably alter drug clearance.

Drugs Affecting Hepatic Microsomal Enzymes

CYP1A2 or glucuronyl transferase enzyme inhibitors and inducers: Potential pharmacokinetic interaction (altered olanzapine metabolism).

Drugs Metabolized by Hepatic Microsomal Enzymes

Inhibitors of CYP 1A2, 2C9, 2C19, 2D6, or 3A: Clinically important pharmacokinetic interactions unlikely.

Specific Drugs

Olanzapine Pharmacokinetics

Absorption

Bioavailability

Well absorbed after oral administration, with peak plasma concentrations attained in approximately 6 hours. About 40% of oral dose is metabolized before reaching systemic circulation.

Steady-state concentrations achieved after approximately 7 days of continuous oral dosing and are approximately twice those observed following single-dose administration.

Exhibits linear and dose-proportional pharmacokinetics when given orally within the clinical dosage range.

Conventional and orally disintegrating olanzapine tablets are bioequivalent.

Fixed-combination olanzapine/fluoxetine capsules: Pharmacokinetics expected to resemble those of the individual components. Olanzapine pharmacokinetics slightly altered, but effects not clinically important.

Short-acting IM olanzapine (Zyprexa IntraMuscular): Rapidly absorbed following IM administration, with peak plasma concentrations occurring within 15–45 minutes. Exhibits linear pharmacokinetics when given IM within the clinical dosage range. A 5-mg IM injection of olanzapine produces, on average, peak plasma concentrations approximately 5 times higher than those produced by a 5-mg dose of oral olanzapine.

Extended-release IM olanzapine pamoate (Zyprexa Relprevv): Following deep IM gluteal administration, slow dissolution of the pamoate ester (which is practically insoluble) results in prolonged plasma olanzapine concentrations over a period of weeks to months. IM injection every 2 or 4 weeks provides plasma olanzapine concentrations similar to those achieved with daily oral dosing. Steady-state olanzapine concentrations achieved with IM dosages of 150–405 mg every 2 or 4 weeks are within the range achieved with oral olanzapine dosages of 5–20 mg daily. Plasma concentrations generally reach a peak within the first week following each injection.

Food

Food does not affect rate or extent of oral absorption.

Distribution

Extent

Extensively distributed throughout the body.

Distributed into milk in humans.

Plasma Protein Binding

93% (mainly to albumin and α₁-acid glycoprotein).

Elimination

Metabolism

Metabolized to inactive metabolites, principally via direct glucuronidation and oxidation via CYP isoenzymes (mainly CYP1A2) and the flavin-containing monooxygenase system, with minor contribution of CYP2D6.

Elimination Route

Excreted in urine (57%) and feces (30%); 7% of dose is excreted in urine as unchanged drug.

Half-life

Oral administration: 21–54 hours.

IM administration of short-acting olanzapine injection: Half-life similar to that observed with oral administration.

IM administration of extended-release olanzapine pamoate injection: Approximately 30 days. Exposure to olanzapine may persist for months after a single long-acting IM injection.

Special Populations

In women, clearance of olanzapine is approximately 30% lower than in men; there were no apparent differences between men and women in efficacy or adverse effects.

In smokers, olanzapine clearance is about 40% higher than in nonsmokers, although dosage adjustment is not routinely recommended.

Combined effects of age, smoking, and gender may contribute to substantial pharmacokinetic differences in populations.

Stability

Storage

Oral

Conventional and Orally Disintegrating Tablets

20–25°C (excursions permitted to 15–30°C). Store orally disintegrating tablets in their original sealed blister. Protect from light and moisture.

Fixed-combination (with Fluoxetine) Capsules

Tight containers at 25°C (excursions permitted to 15–30°C). Keep container tightly closed and protect from moisture.

Parenteral

Immediate-release Olanzapine Powder for IM Injection (e.g., Zyprexa IntraMuscular)

20–25°C (excursions permitted to 15–30°C). Protect from light and avoid freezing.

Reconstituted solution may be stored for up to 1 hour at 20–25°C, if necessary; after 1 hour, discard any unused portion.

Extended-release Olanzapine Pamoate Powder for IM Injection (Zyprexa Relprevv)

Store at room temperature (not to exceed 30°C).

Reconstituted suspension may be stored for up to 24 hours at room temperature; once withdrawn into syringe for administration, use immediately.

Actions

• Atypical antipsychotic agent.

• Exact mechanism of action for labeled indications has not been fully elucidated; may involve antagonism at serotonin type 2 and dopamine receptors in schizophrenia.

• Acts as an antagonist with high binding affinity for 5-HT_2A/2C, 5-HT₆, D_1-4, histamine H₁ receptors, and adrenergic α₁ receptors.

• Moderate affinity for 5-HT₃ and muscarinic M_1-5 receptors.

• Possesses little or no affinity for β-adrenergic, γ-aminobutyric acid (GABA) A, or benzodiazepine receptors.

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (medication guide) for oral olanzapine formulations and the extended-release injectable formulation of the drug (Zyprexa Relprevv).

• Patients and caregivers should be advised that geriatric patients with dementia-related psychosis treated with antipsychotic agents are at an increased risk of death. Patients and caregivers should also be advised that geriatric patients with dementia-related psychosis treated with olanzapine had a significantly higher incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack) compared with placebo. Olanzapine is not approved for geriatric patients with dementia-related psychosis.

• During premarketing clinical studies, reactions that presented with signs and symptoms consistent with olanzapine overdose have been reported in patients following an injection of long-acting IM olanzapine pamoate (Zyprexa Relprevv). It is mandatory that patients be enrolled in the Zyprexa Relprevv Patient Care Program to receive treatment. Patients should be advised of the risk of post-injection delirium/sedation syndrome each time they receive an injection. Patient and caregivers should be advised that after each injection, patients must be observed at the healthcare facility for at least 3 hours and must be accompanied to their destination upon leaving the facility. The medication guide should be distributed each time patients receive an injection.

• Patients and caregivers should be counseled that a potentially fatal symptom complex sometimes referred to as neuroleptic malignant syndrome (NMS) has been reported in association with administration of antipsychotic agents, including olanzapine. Signs and symptoms of NMS include hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia).

• Patients should be advised to report to their healthcare provider at the earliest onset of any signs and symptoms that may be associated with drug reaction with eosinophilia and systemic symptoms (DRESS).

• Patients should be advised of the potential risk of hyperglycemia-related adverse reactions. Patients should be monitored regularly for worsening of glucose control. Patients who have diabetes should follow their clinician’s instructions about how often to check their blood sugar while taking olanzapine.

• Patients should be counseled that dyslipidemia has occurred during treatment with olanzapine. Patients should have their lipid profile monitored regularly.

• Patients should be counseled that weight gain has occurred during treatment with olanzapine. Patients should have their weight monitored regularly.

• Patients should be advised of the risk of orthostatic hypotension, especially during the period of initial dose titration and in association with the use of concomitant drugs that may potentiate the orthostatic effect of olanzapine (e.g., diazepam, alcohol). Patients should be advised to change positions carefully to help prevent orthostatic hypotension, and to lie down if they feel dizzy or faint, until they feel better. Patients should be advised to call their clinician if they experience any of the following signs and symptoms associated with orthostatic hypotension: dizziness, fast or slow heartbeat, or fainting.

• Because 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. Additionally, due to the risk of post-injection delirium/sedation syndrome, patients should not drive or operate heavy machinery for the remainder of the day of each injection of Zyprexa Relprevv.

• Patients should be advised regarding appropriate care in avoiding overheating and dehydration. Patients should be advised to call their clinician right away if they become severely ill and have some or all of these symptoms of dehydration: sweating too much or not at all, dry mouth, feeling very hot, feeling thirsty, not able to produce urine.

• Patients should be advised to inform their healthcare providers if they are taking, or plan to take, other olanzapine-containing drugs, including Symbyax. Patients should also be advised to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses.

• Patients should be advised to avoid alcohol while taking olanzapine.

• Olanzapine orally disintegrating tablets contain phenylalanine (0.34, 0.45, 0.67, or 0.90 mg per 5, 10, 15, or 20 mg tablet, respectively).

• Advise women to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with olanzapine. Advise patients that olanzapine may cause extrapyramidal and/or withdrawal symptoms (agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder) in a neonate. Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to olanzapine during pregnancy.

• Advise breastfeeding women receiving olanzapine to monitor infants for excess sedation, irritability, poor feeding, and extrapyramidal symptoms (tremors and abnormal muscle movements) and to seek medical care if they notice these signs.

• Advise females of reproductive potential that olanzapine may impair fertility due to an increase in serum prolactin levels. The effects on fertility are reversible.

• Advise patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Long-acting IM olanzapine pamoate (Zyprexa Relprevv) is available only through a restricted distribution program.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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