Dosing & Uses
Dosage Forms & Strengths
tablet
- 2.5mg
- 5mg
- 7.5mg
- 10mg
- 15mg
- 20mg
tablet, orally disintegrating
- 5mg
- 10mg
- 15mg
- 20mg
IM injection, short-acting
- 10mg
IM injection, extended-release suspension
- 210mg/vial
- 300mg/vial
- 405mg/vial
Schizophrenia
PO
- 5-10 mg/day initially; if necessary, may be titrated upward in increments of 5 mg/day at intervals >1 week
- Maintenance: 10-20 mg/day; not to exceed 20 mg/day
Recommended IM, extended-release dose based on oral dosage
- Oral dosage 10 mg/day: 210 mg IM every 2 weeks or 405 mg IM every 4 weeks for 1st 8 weeks, then 150 mg every 2 weeks or 300 mg every 4 weeks
- Oral dosage 15 mg/day: 300 mg IM every 2 weeks for 1st 8 weeks, then 210 mg every 2 weeks or 405 mg every 4 weeks
- Oral dosage 20 mg/day: 300 mg IM every 2 weeks for 1st 8 weeks, then 300 mg every 2 weeks
Bipolar Mania
Indicated for acute/maintenance treatment of manic or mixed episodes associated with bipolar 1 disorder; may be used adjunctively to valproate or lithium in the treatment of manic or mixed episodes associated with bipolar disorder
Monotherapy: 10-15 mg/day PO initially; may be titrated upward in increments of 5 mg/day at intervals >24 hr
Adjunct to lithium or valproate: 10 mg/day PO initially
Maintenance: 5-20 mg/day PO; not to exceed 20 mg/day
Agitation Associated with Schizophrenia and Bipolar I Mania
IM, short-acting: 2.5-10 mg/dose; additional doses (up to 10 mg) may be considered; administer subsequent doses 2 hr after initial dose and 4 hr after 2nd dose if necessary; not to exceed 30 mg/day
See Dosing Considerations
Bipolar Depression
Indicated for depressive episodes associated with bipolar I disorder in combination with fluoxetine
5 mg PO in evening; adjusted to range of 5-12.5 mg/day
Safety of coadministered doses greater than olanzapine 18 mg with fluoxetine 75 mg have not been evaluated
Chemotherapy Associated Nausea or Vomiting (Off-label)
Off-label use for prevention of chemotherapy associated nausea or vomiting in combination with 5-HT3 antagonist and dexamethasone (N Engl J Med 2016;375[2]:134-42)
Breakthrough nausea and vomiting: 5-10 mg PO qDay for 3 days, when not used for acute and delayed emesis prevention
Acute and delayed emesis prevention
- Off-label use for prevention of chemotherapy associated nausea or vomiting in combination with 5-HT3 antagonist and dexamethasone
- In combination with dexamethasone and a 5-HT3 antagonist (eg, palonosetron, aprepitant)
- High emetic risk IV chemotherapy: 10 mg PO the day of chemotherapy (day 1), followed by 10 mg PO qDay (days 2-4)
- Moderate emetic risk IV chemotherapy: 10 mg PO the day of chemotherapy (day 1), followed by 10 mg PO qDay (days 2-3)
References
- J Clin Oncol 2017 Jul 31 (ASCO clinical practice guideline update) Support Care Cancer 2017;25(2):607-613 N Engl J Med 2016;375(2):134-42
Dosing Modifications
Renal impairment: Dose adjustment not necessary
Hepatic impairment: Dose adjustment may be necessary; use caution
Slow metabolism, initial dose for schizophrenia
- Initiate with 5 mg PO qDay for patients with risk factors which may slow olanzapine metabolism (eg, nonsmoking females ≥65 yr)
- Dose escalation should performed with caution
Dosing Considerations
Dosage adjustments, if necessary, should be made at intervals >24 hr
Dosage Forms & Strengths
tablet
- 2.5mg
- 5mg
- 7.5mg
- 10mg
- 15mg
- 20mg
tablet, orally disintegrating
- 5mg
- 10mg
- 15mg
- 20mg
Bipolar I Disorder (Manic or Mixed Episodes)
<13 years: Safety and efficacy not established
13-17 years: 2.5-5 mg/day PO initially; target dosage, 10 mg/day; adjust by increments/decrements of 2.5-5 mg; dosage range, 2.5-20 mg/day
Schizophrenia
<13 years: Safety and efficacy not established
13-17 years: 2.5-5 mg/day PO initially; target dosage, 10 mg/day; adjust by increments/decrements of 2.5-5 mg; dosage range, 2.5-20 mg/day
Bipolar Depression
Indicated for depressive episodes associated with bipolar I disorder in combination with fluoxetine
<10 years: Safety and efficacy not established
10-17 years: 2.5 mg PO qPM and fluoxetine 20 mg PO qPM initially; dosage adjustments, if indicated, should be made to individual components according to efficacy and tolerability
Safety of coadministered doses greater than olanzapine 12 mg with fluoxetine 50 mg have not been in pediatric clinical studies
Stuttering (Off-label)
≤12 years: 1.25 mg PO at bedtime for 4 weeks, then 2.5 mg at bedtime
>12 years: 2.5 mg PO at bedtime for 4 weeks, then 5 mg at bedtime
Not approved for dementia-related psychosis, because of increased risk of cardiovascular or infection-related mortality (see Black Box Warnings)
Consider lower starting dosage
Schizophrenia
2.5-5 mg/day PO initially
IM (extended-release): 150 mg every 4 weeks in patients who are debilitated or predisposed to hypotensive episodes; not studied in patients with renal or hepatic impairment; requires deep IM administration (muscle mass in elderly may be sufficient)
Schizophrenia or Bipolar-Related Agitation
IM (short-acting): 5 mg; consider 2.5 mg if patient is predisposed to hypotensive reactions
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
Orthostatic hypotension (≥20%)
Weight gain, dose dependent (5-40%)
Hypertriglyceridemia (≤39%)
Hypercholesterolemia (≤39%)
Somnolence, dose dependent (6-39%)
Extrapyramidal symptoms (EPS), dose dependent (15-32%)
Xerostomia (9-22%)
Weakness (2-20%)
Dizziness (4-18%)
Accidental injury (12%)
Insomnia (12%)
Elevated alanine aminotransferase (ALT) level (5-12%)
Constipation (9-11%)
Dyspepsia (7-11%)
Hyperprolactinemia (30%)
Hyperglycemia (12.8%)
1-10%
Hypotension (2%)
Postural hypotension (1%)
Tremor (1%)
Asthenia (2%)
Akathisia reactions (2%)
Parkinsonism reactions (4%)
<1%
Syncope
Sudden cardiac death
Hyperglycemia
Diabetic coma with ketoacidosis
Diabetic ketoacidosis
Acute hemorrhagic pancreatitis
Venous thromboembolism
Immune hypersensitivity reaction
Cerebrovascular disease
Seizure, status epilepticus
Suicidal intent
Pulmonary embolism
Death
Neuroleptic malignant syndrome (NMS)
Tardive dyskinesia
Postmarketing Reports
Eosinophilia and Systemic Symptoms (DRESS)
Falls
Restless legs syndrome
Warnings
Black Box Warnings
Not approved for dementia-related psychosis; elderly patients with dementia-related psychosis who are treated with antipsychotic drugs are at increased risk of death, as shown in short-term controlled trials; in these trials, deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature
Patients are at risk for severe sedation (including coma) or delirium after each injection and must be observed for at least 3 hours in registered facility with ready access to emergency response services
Because of this risk, olanzapine is available only through restricted distribution program
Contraindications
Documented hypersensitivity
Refer to the package insert for Symbyax contraindications, when using PO olanzapine and fluoxetine in combination
Cautions
Possibility of suicide attempt is inherent in schizophrenia and bipolar I disorder, and close supervision of high-risk patients should accompany drug therapy; when using in combination with fluoxetine, also refer to Boxed Warning and Precautions sections of package insert for Symbyax
Irreversible, involuntary, dyskinetic movements may develop with antipsychotic drugs; prevalence appears to be highest among elderly individuals, especially elderly women; discontinue if clinically appropriate
Tardive dyskinesia may remit, partially or completely, if antipsychotic treatment withdrawn; however, antipsychotic treatment, itself, may suppress (or partially suppress) signs and symptoms of syndrome and possibly mask underlying process; effect symptomatic suppression has upon long-term course of syndrome unknown
Neutropenia, leukopenia, and agranulocytosis reported; discontinue therapy at first sign of blood dyscrasias or if absolute neutrophil count <1000/mm³
Cerebrovascular effects including, stroke and transient ischemic attack resulting in death reported
FDA warning regarding off-label use for dementia in elderly (see Black Box Warnings)
Use caution in patients with history of seizures or with conditions that potentially lower seizure threshold
Changes from normal to high prolactin levels observed in controlled studies (incidence, 30%)
Use caution with strenuous exercise, dehydration, heat exposure, and medications with anticholinergic effects; impaired core body temperature regulation may occur
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) 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 suspected
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
Has potential to impair judgment, thinking, and motor skills; use caution when operating machinery
Olanzapine indicated as integral part of comprehensive treatment program for pediatric patients with schizophrenia and bipolar disorder, which may include other measures (eg, psychological, educational, social) as well IM, extended-release: Risk of postinjection delirium/sedation syndrome, availability is restricted and requires registration (call 877-772-9390)
Use in patients with concomitant illnesses
- Use caution in patients with clinically significant prostatic hypertrophy, narrow angle glaucoma, or a history of paralytic ileus or related conditions; olanzapine exhibits in vitro muscarinic activity
- May induce orthostatic hypotension associated with dizziness, tachycardia, bradycardia and, in some patients, syncope, especially during initial dose-titration period, probably as consequence of alpha1-adrenergic antagonistic propertie
Metabolic changes
-
Weight gain
- Increased potential (in adolescents as compared with adults) for weight gain and hyperlipidemia; clinicians prescribing to adolescents should consider potential long-term risks, which in many cases may lead them to prescription of other drugs first in this population
- Appropriate clinical monitoring is recommended, including fasting blood lipid testing at the beginning of, and periodically during, treatment
-
Hyperglycemia and diabetes mellitus
- Consider risks and benefits when prescribing olanzapine to patients with diabetes mellitus, or borderline increased blood glucose level (fasting 100-126 mg/dL, nonfasting 140-200 mg/dL); monitor regularly for worsening of glucose control; 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
Neuroleptic malignant syndrome
- NMS have been reported in association with atypical antipsychotic administration (eg, olanzapine)
- Symptoms includes hyperpyrexia, muscle rigidity; altered mental status and evidence of autonomic instability
- Management of NMS should include immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; intensive symptomatic treatment and medical monitoring; and treatment of any concomitant serious medical problems for which specific treatments are available
- If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered and monitored
Pregnancy & Lactation
Pregnancy category: C
Neonates exposed to antipsychotic drugs during 3rd trimester of pregnancy are at risk for EPS or withdrawal symptoms after delivery; these complications vary in severity, with some being self-limited and others requiring ICU support and prolonged hospitalization
Lactation: Drug enters breast milk; not recommended
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
May act through combination of dopamine and serotonin type 2 receptor site antagonism
Absorption
Peak plasma time: 6 hr (PO); 15-45 min (short-acting IM); 7 days (extended-release IM)
Distribution
Protein bound: 93%
Vd: 1000 L
Metabolism
Extensively metabolized through direct glucuronidation and CYP450 oxidation
Metabolites: Inactive
Elimination
Half-life: 21-54 hr (immediate release); 30 days (extended release)
Excretion: Urine (57%), feces (30%)
Administration
Oral administration
May take with or without food
Oral disintegrating tablets
- After opening sachet, peel back foil on blister; do not push tablet through foil
- Immediately upon opening the blister, using dry hands, remove tablet and place entire tablet in the mouth
- Tablet disintegration occurs rapidly in saliva so it can be easily swallowed with or without liquid
IM Administration
Short-acting and extended-release IM preparations are not interchangeable
Short-acting: Dissolve in 2.1 mL SWI to yield 5 mg/mL solution; inject deep and slow within 1 hr of reconstitution
Extended-release: Reconstitute with supplied diluent (210-mg vial in 1.3 mL; 300-mg vial in 1.8 mL; 405-mg vial in 2.3 mL); inject deep in gluteal muscle
Do not use lorazepam injection for reconstitution, and do not mix with haloperidol or diazepam in syringe
Storage
tablets and oral disintegrating tablets
- Store at room temperature, 68-77°F (20-25°C)
- Protect from light and moisture
IM, short-acting
- Before reconstitution: Store at room temperature, 68-77°F (20-25°C)
- Reconstituted vial: Store at room temperature, 68-77°F (20-25°C) for up to 1 hr if necessary
- Discard any unused portion of reconstituted vial
- Protect from light, do not freeze.
IM, extended-release
- Before reconstitution: Store at room temperature not to exceed 30°C (86°F)
- Suspended solution: Store at room temperature for up to 24 hr if necessary
- Immediately agitate prior to product withdrawal; administer immediately once suspension is withdrawn into syringe
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Patient Handout
Formulary
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