oh-LAN-za-peen

Therapeutic Classification: antipsychotics

Pharmacologic Classification: thienobenzodiazepines

• 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.

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

• Decreased manifestations of psychoses.

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.

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.

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.

(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].

• Assess mental status (orientation, mood, behavior) before and periodically during therapy. Monitor closely for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.
  • Monitor BP (sitting, standing, lying), ECG, pulse, and respiratory rate before and frequently during dose adjustment.
  • Assess weight and BMI initially and throughout therapy.
  • Observe patient carefully when administering medication to ensure that medication is taken and not hoarded or cheeked.
  • Assess fluid intake and bowel function. Increased bulk and fluids in the diet may help minimize constipation.
  • Monitor patient for onset of akathisia (restlessness or desire to keep moving) and extrapyramidal side effects (parkinsonian: difficulty speaking or swallowing, loss of balance control, pill rolling of hands, mask-like face, shuffling gait, rigidity, tremors; and dystonic: muscle spasms, twisting motions, twitching, inability to move eyes, weakness of arms or legs) every 2 mo during therapy and 8–12 wk after therapy has been discontinued. Report these symptoms if they occur, as reduction in dose or discontinuation of medication may be necessary. Trihexyphenidyl or benztropine may be used to control symptoms.
  • Monitor for tardive dyskinesia (uncontrolled rhythmic movement of mouth, face, and extremities; lip smacking or puckering; puffing of cheeks; uncontrolled chewing; rapid or worm-like movements of tongue, excessive blinking of eyes). Discontinue olanzapine and report immediately; may be irreversible.
  • Monitor for development of neuroleptic malignant syndrome (fever, respiratory distress, tachycardia, seizures, diaphoresis, hypertension or hypotension, pallor, tiredness, severe muscle stiffness, loss of bladder control). Notify health care professional immediately if these symptoms occur.
• Monitor for symptoms related to hyperprolactinemia (menstrual abnormalities, galactorrhea, sexual dysfunction).
• Assess for falls risk. Drowsiness, orthostatic hypotension, and motor and sensory instability increase risk. Institute prevention if indicated.
• Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, and/or facial swelling), associated with involvement of other organ systems (hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis) during therapy. May resemble an acute viral infection. Eosinophilia is often present. Discontinue therapy if signs occur.
• Zyprexa Relprevv: Observe for signs and symptoms of Post-injection Delirium/Sedation Syndrome (dizziness, confusion, disorientation, slurred speech, altered gait, difficulty ambulating, weakness, agitation, extrapyramidal symptoms, hypertension, convulsion, reduced level of consciousness ranging from mild sedation to coma) for at least 3 hr after injection.

• Evaluate CBC, liver function tests, and ocular examinations periodically during therapy. May cause ↓ platelets. May cause ↑ bilirubin, AST, ALT, GGT, CK, and alkaline phosphatase.
  • Monitor blood glucose prior to and periodically during therapy.
  • Monitor serum prolactin prior to and periodically during therapy. May cause ↑ serum prolactin levels.
  • Monitor CBC frequently during initial mo of therapy in patients with pre-existing or history of low WBC. May cause leukopenia, neutropenia, or agranulocytosis. Discontinue therapy if this occurs.
  • May cause hyperlipidemia; monitor serum lipids prior to and periodically during therapy.

• Do not confuse Zyprexa with Celexa, Zyrtec, Zestril, or Zelapar. Do not confuse olanzapine with quetiapine.
• REMS: Zyprexa Relprevv is only prescribed through the Zyprexa Relprevv Patient Care Program. Prescribers, pharmacies, and patients must be educated about the program and must comply with the program requirements.
• PO: May be administered without regard to meals.
  • For orally disintegrating tablets, peel back foil on blister, do not push tablet through foil. Using dry hands, remove from foil and place entire tablet in mouth. Tablet will disintegrate with or without liquid.
• IM: Reconstitution: Reconstitute with 2.1 mL of sterile water for injection for a concentration of 5 mg/mL. Solution should be clear and yellow; do not administer solutions that are discolored or contain particulate matter.Inject slowly, deep into muscle. Do not administer IV or SUBQ. Administer within 1 hr of reconstitution. Discard unused solution.
  • For Zyprexa Relprevv: Use gloves when preparing; solution may be irritating to skin. Reconstitution: Use only diluent provided by manufacturer. Reconstitute 150-mg or 210-mg dose with 1.3 mL, 300 mg with 1.8 mL, and 405 mg with 2.3 mL of diluent. Loosen powder by tapping vial; inject diluent into powder. Remove needle from vial holding vial upright to prevent loss of solution. Engage needle safety device as explained by manufacturer. Pad a hard surface and tap vial repeatedly until no powder or yellow, dry clumps are visible. Shake vial vigorously until suspension appears smooth and consistent in color and texture. Solution will be yellow and opaque. Allow foam to dissipate. Suspension is stable for 24 hr at room temperature; if not used immediately, shake to resuspend. 150 mg/mL. Replace needle with 19 gauge, 1.5 in. or 2 in. for obese patients. Slowly withdraw desired amount from vial; 150 mg = 1 mL, 210 mg = 1.4 mL, 300 mg = 2 mL, 405 mg = 2.7 mL. Administer immediately deep IM gluteal after withdrawing. Do not massage injection site. Patient must be observed for at least 3 hr after injection for Post-Injection Delirium/Sedation Syndrome.

• 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.

• Decrease in excitable, manic behavior.
• Decrease in positive symptoms (delusions, hallucinations) of schizophrenia.
• Decrease in negative symptoms (social withdrawal, flat, blunted affect) of schizophrenia.
• Increased sense of well-being.
• Decreased agitation.

ZyPREXA, ZyPREXA Relprevv, ZyPREXA Zydis