• PO, IM: Schizophrenia.
• PO: Management of the following:
  • Acute therapy of manic or mixed episodes associated with bipolar I disorder (as monotherapy [adults and adolescents] or in combination with lithium or evaporate [adults only]);
  • Maintenance therapy of bipolar I disorder;
  • Depressive episodes associated with bipolar I disorder (in combination with fluoxetine);
  • Treatment-resistant depression (in combination with fluoxetine).
• IM: Acute agitation due to schizophrenia or bipolar I mania.

Unlabeled Uses:

• Anorexia nervosa.
• Treatment of nausea and vomiting related to highly emetogenic chemotherapy.

Contraindicated in:

• Hypersensitivity
• Phenylketonuria (orally disintegrating tablets contain aspartame).

Use Cautiously in:

• Hepatic impairment
• Patients at risk for aspiration or falls
• Cardiovascular or cerebrovascular disease
• History of seizures
• History of attempted suicide
• Diabetes or risk factors for diabetes (may worsen glucose control)
• Presence/history of constipation, urinary retention, prostatic hypertrophy, or paralytic ileus
• Low WBC or ANC or history of drug-induced neutropenia/leukopenia
• Angle-closure glaucoma
• OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk; neonates at ↑ risk for extrapyramidal symptoms and withdrawal after delivery when exposed during the 3rd trimester
• Lactation: Use while breastfeeding only if potential maternal benefit justifies potential fetal risk
• Pedi: Children <13 yr (safety and effectiveness not established); adolescents at ↑ risk for weight gain and hyperlipidemia
• Geri: Appears on Beers list. ↑ risk of stroke, cognitive decline, and mortality in older adults with dementia. Avoid use in older adults, except for schizophrenia, bipolar disorder, or adjunctive treatment of major depressive disorder.

CV: orthostatic hypotension, bradycardia, chest pain, syncope, tachycardia.

Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), photosensitivity.

EENT: amblyopia, rhinitis, ↑ salivation, pharyngitis.

Endo: galactorrhea, goiter, gynecomastia, hyperglycemia, hyperprolactinemia.

F and E: ↑thirst.

GI: ↑liver enzymes, constipation, dry mouth, weight loss, abdominal pain, dysphagia, nausea.

GU: ↓fertility (females), ↓ libido, amenorrhea, impotence, urinary incontinence.

Hemat: AGRANULOCYTOSIS, leukopenia, neutropenia.

Metab: weight gain, ↑ appetite, dyslipidemia.

MS: hypertonia, joint pain.

Neuro: agitation, delirium, dizziness, headache, restlessness, sedation, tremor, weakness, dystonia, falls, insomnia, mood changes, NEUROLEPTIC MALIGNANT SYNDROME, personality disorder, SEIZURES, speech impairment, SUICIDAL THOUGHTS, tardive dyskinesia.

Resp: aspiration, cough, dyspnea.
Misc: body temperature dysregulation, fever, flu-like syndrome.

Drug-Drug:

• ↑anticholinergic effects with other anticholinergic drugs, including antihistamines, quinidine, disopyramide, and antidepressants; avoid concurrent use.
• Effects may be ↓ by concurrent carbamazepine, omeprazole, or rifampin.
• Antihypertensives and CNS depressants may ↑ risk of orthostatic hypotension.
• ↑CNS depression may occur with concurrent use of alcohol or other CNS depressants; concurrent use of IM olanzapine and parenteral benzodiazepines should be avoided.
• May antagonize the effects of levodopa or other dopamine agonists.
• Fluvoxamine may ↑ levels.
• Nicotine can ↓ olanzapine levels.

(Generic available)

• Tablets: 2.5 mg; 5 mg; 7.5 mg; 10 mg; 15 mg; 20 mg;
• Orally disintegrating tablets (Zyprexa Zydis): 5 mg; 10 mg; 15 mg; 20 mg;
• Powder for injection: 10 mg/vial;
• Extended-release powder for suspension for injection (Zyprexa Relprevv): 210 mg/vial; 300 mg/vial; 405 mg/vial;
• In combination with: fluoxetine (Symbyax); samidorphan (Lybalvi). See Appendix [not included in this PDA edition].

Schizophrenia

• PO (Adults — Most Patients): 5–10 mg/day initially; may ↑ at weekly intervals by 5 mg/day (target dose = 10 mg/day; not to exceed 20 mg/day).
• PO (Adults — Debilitated or Nonsmoking Female Patients 65 yr): Initiate therapy at 5 mg/day.
• PO (Children 13–17 yr): 2.5–5 mg/day initially; may ↑ at weekly intervals by 2.5–5 mg/day (target dose = 10 mg/day; not to exceed 20 mg/day).
• IM (Adults): Oral olanzapine dose = 10 mg/day: 210 mg every 2 wk or 410 mg every 4 wk for the first 8 wk, then 150 mg every 2 wk or 300 mg every 4 wk as maintenance therapy; Oral olanzapine dose = 15 mg/day: 300 mg every 2 wk for the first 8 wk, then 210 mg every 2 wk or 405 mg every 4 wk as maintenance therapy; Oral olanzapine dose = 20 mg/day: 300 mg every 2 wk for the first 8 wk, then 300 mg every 2 wk as maintenance therapy.
• IM (Adults — Debilitated or Nonsmoking Female Patients 65 yr): Initiate therapy at 150 mg every 4 wk.

Acute Manic or Mixed Episodes Associated With Bipolar I Disorder

• PO (Adults): 10–15 mg/day initially (use 10 mg/day when used with lithium or evaporate); may ↑ every 24 hr by 5 mg/day (not to exceed 20 mg/day).
• PO (Children 13–17 yr): 2.5–5 mg/day initially; may ↑ by 2.5–5 mg/day (target dose = 10 mg/day; not to exceed 20 mg/day).

Maintenance Treatment of Bipolar I Disorder

• PO (Adults): Continue at the dose required to maintain symptom remission (usual dose: 5–20 mg/day).
• PO (Children 13–17 yr): Continue at the lowest dose required to maintain symptom remission.

Acute Agitation due to Schizophrenia or Bipolar I Mania

• IM (Adults): 10 mg, may repeat in 2 hr, then 4 hr later.
• IM (Adults >65 yr): Initiate therapy with 5 mg.

Depressive Episodes Associated With Bipolar I Disorder

• PO (Adults): 5 mg/day with fluoxetine 20 mg/day (both given in evening); may ↑ fluoxetine dose up to 50 mg/day and olanzapine dose up to 12.5 mg/day.
• PO (Children 10–17 yr): 20 mg/day with olanzapine 2.5 mg/day (both given in evening); may ↑ fluoxetine dose up to 50 mg/day and olanzapine dose up to 12 mg/day.

Treatment-Resistant Depression

• PO (Adults): 5 mg/day with fluoxetine 20 mg/day (both given in evening); may ↑ fluoxetine dose up to 50 mg/day and olanzapine dose up to 20 mg/day.

ZyPREXA, ZyPREXA Relprevv, ZyPREXA Zydis

• Antagonizes dopamine and serotonin type 2 in the CNS.
• Also has anticholinergic, antihistaminic, and anti–alpha₁-adrenergic effects.

• Decreased manifestations of psychoses.

Therapeutic Classification: antipsychotics

Pharmacologic Classification: thienobenzodiazepines

Absorption: Well absorbed but rapidly metabolized by first-pass effect, resulting in 60% bioavailability. Conventional tablets and orally disintegrating tablets (Zydis) are bioequivalent. IM administration results in significantly higher blood levels (5 times that of oral).

Distribution: Extensively distributed.

Protein Binding: 93%.

Metabolism/Excretion: Primarily metabolized by the liver by the CYP1A2 isoenzyme; 7% excreted unchanged in urine.

Half-life: 21–54 hr.

(antipsychotic effects)

*Blood levels.

• REMS: Advise patient to take medication as directed and not to skip doses or double up on missed doses. May need to discontinue gradually. Advise patient to read the Medication Guide prior to starting therapy and with each Rx refill in case of changes. Explain the Zyprexa Relprevv Patient Care Program to patient and encourage patient to enroll in the Zyprexa Relprevv Patient Care Program registry.
• Inform patient of possibility of extrapyramidal symptoms and tardive dyskinesia. Instruct patient to report these symptoms immediately to health care professional.
• Advise patient to change positions slowly to minimize orthostatic hypotension. Protect from falls.
• Medication may cause drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to the medication is known. Patients receiving Zyprexa Relprevv should not drive for 24 hr following injection.
• Advise patient and family to notify health care professional if thoughts about suicide or dying, attempts to commit suicide; new or worse depression; new or worse anxiety; feeling very agitated or restless; panic attacks; trouble sleeping; new or worse irritability; acting aggressive; being angry or violent; acting on dangerous impulses; an extreme increase in activity and talking, other unusual changes in behavior or mood occur.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications and alcohol.
• Advise patient to use sunscreen and protective clothing when exposed to the sun. Extremes of temperature (exercise, hot weather, hot baths, or showers) should also be avoided; this drug impairs body temperature regulation.
• Instruct patient to use saliva substitute, frequent mouth rinses, good oral hygiene, and sugarless gum or candy to minimize dry mouth. Consult dentist if dry mouth continues for >2 wk.
• Advise patient to notify health care professional of medication regimen before treatment or surgery.
• Instruct patient to notify health care professional promptly if sore throat, fever, unusual bleeding or bruising, rash, symptoms of Post-Injection Delirium/Sedation Syndrome, or weakness, tremors, visual disturbances, dark-colored urine, clay-colored stools, menstrual abnormalities, galactorrhea, or sexual dysfunction occur.
• Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, and to avoid breastfeeding during therapy. Encourage women who become pregnant while taking olanzapine to enroll in the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit womensmentalhealth.org/research/pregnancyregistry/. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. Monitor infants exposed through breastfeeding for excess sedation, irritability, poor feeding, and extrapyramidal symptoms (tremors and abnormal muscle movements).
• Emphasize the importance of routine follow-up exams and continued participation in psychotherapy.

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