olanzapine (Rx)

Brand and Other Names:Zyprexa, Zyprexa Relprevv, more...Zyprexa Zydis
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Dosing & Uses

AdultPediatricGeriatric

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
more...

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
more...

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

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Interactions

Interaction Checker

and olanzapine

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    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            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

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            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

            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
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            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.

            more...
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            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%)

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            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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            Images

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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