Olanzapine

Olanzapine is used to treat certain mental/mood conditions (such as schizophrenia, bipolar disorder). It may also be used in combination with other medication to treat depression. This medication can help to decrease hallucinations and help you to think more clearly and positively about yourself, feel less agitated, and take a more active part in everyday life.

Olanzapine belongs to a class of drugs called atypical antipsychotics. It works by helping to restore the balance of certain natural substances in the brain.

Talk to the doctor about the risks and benefits of treatment (especially when used in teenagers).

Olanzapine is available under the following different brand and other names: Zyprexa, Zyprexa Relprevv, Zyprexa Zydis.

Adult Dosage Forms & Strengths

Tablet

• 2.5 mg
• 5 mg
• 7.5 mg
• 10 mg
• 15 mg
• 20 mg

Tablet, orally disintegrating

• 5 mg
• 10 mg
• 15 mg
• 20 mg

Intramuscular (IM) injection, short-acting

• 10 mg

Intramuscular (IM), extended-release suspension

• 210 mg/vial
• 300 mg/vial
• 405 mg/vial

Pediatric Dosage Forms & Strengths

Tablet

• 2.5 mg
• 5 mg
• 7.5 mg
• 10 mg
• 15 mg
• 20 mg

Tablet, orally disintegrating

• 5 mg
• 10 mg
• 15 mg
• 20 mg

Dosage Considerations – Should be Given as Follows:

Schizophrenia in Adults

Taken orally

• 5-10 mg per day initially; if necessary, maybe titrated upward in increments of 5 mg per day at intervals greater than 1 week
• Maintenance: 10-20 mg per day; not to exceed 20 mg per day

Intramuscular (IM), extended-release

• Recommended dosing based on oral dosing
• Oral dosage 10 mg per day: Give 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 per day: Give 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 per day: Give 300 mg IM every 2 weeks for 1st 8 weeks, then 300 mg every 2 weeks

Schizophrenia in Children

Less than 13 years: Safety and efficacy not established

• 13-17 years: 2.5-5 mg per day taken orally initially
• target dosage, 10 mg per day
• adjust by increments/decrements of 2.5-5 mg; dosage range, 2.5-20 mg per day

Bipolar Mania in Adults

Used as monotherapy or in combination with lithium or valproate

• Monotherapy: 10-15 mg/day taken orally initially
• Adjunct to lithium or valproate: 10 mg/day taken orally initially
• Maintenance: 5-20 mg/day taken orally; not to exceed 20 mg/day

Depression in bipolar disorder

• Use in combination with fluoxetine
• 5 mg in the evening; adjusted to a range of 5-12.5 mg/day; may be increased up to 20 mg/day in resistant depression

Dosing considerations

• Dosage adjustments, if necessary, should be made at intervals greater than 24 hours

Schizophrenia or Bipolar-Related Agitation in Adults

• 10 mg IM (short-acting)
• Consider 5-7.5 mg for geriatric patients or if circumstances warrant
• Subsequent IM doses up to 10 mg may be administered 2 hours after 1st dose and 4 hours after 2nd dose; not to exceed 30 mg/day

Bipolar I Disorder (Manic or Mixed Episodes) in Children

Less than 13 years: Safety and efficacy not established

• 13-17 years: 2.5-5 mg/day taken orally initially
• target dosage, 10 mg/day
• Adjust by increments/decrements of 2.5-5 mg
• Dosage range, 2.5-20 mg/day

Stuttering (Off-label) in Children

Children 12 years of age or under

• 1.25 mg taken orally at bedtime for 4 weeks, then 2.5 mg at bedtime

Children older than 12 years of age

• 2.5 mg taken orally at bedtime for 4 weeks, then 5 mg at bedtime

• Renal impairment: Dose adjustment not necessary
• Hepatic impairment: Dose adjustment may be necessary; use caution

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 hour 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 the syringe

Geriatric Dosing Considerations

• Not approved for dementia-related psychosis, because of increased risk of cardiovascular or infection-related mortality
• Consider lower starting dosage

Schizophrenia

• 2.5-5 mg/day taken orally 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 a patient is predisposed to hypotensive reactions

Side effects of olanzapine include:

• Dizziness/low blood pressure upon standing
• Weight gain, dose dependent
• High levels of triglycerides in the blood
• High cholesterol
• Drowsiness, dose dependent
• Extrapyramidal symptoms (EPS), dose dependent (muscle spasms, jerky movements, slow movements)
• Dry mouth
• Weakness
• Dizziness
• Accidental injury
• Insomnia
• Elevated alanine aminotransferase (ALT) level
• Constipation
• Indigestion
• Elevated levels of prolactin in the blood
• High blood sugar
• Low blood pressure
• Tremor
• Weakness
• Restlessness
• Parkinsonism reactions

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

Severe interactions of olanzapine include:

There are no known severe reactions from the use of olanzapine.

Serious interactions of olanzapine include:

• apomorphine
• bromocriptine
• cabergoline
• dopamine
• fluvoxamine
• levodopa
• lisuride
• mefloquine
• methyldopa
• ondansetron
• pefloxacin
• pramipexole
• ropinirole
• sodium oxybate
• umeclidinium bromide/vilanterol inhaled
• vilanterol/fluticasone furoate inhaled

Moderate interactions:

Olanzapine has known moderate interactions with at least 293 different drugs.

Mild interactions:

• brimonidine
• chasteberry
• ethanol
• eucalyptus
• omeprazole
• ruxolitinib
• sage

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

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 (e.g., heart failure, sudden death) or infectious (e.g., 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.

This medication contains olanzapine. Do not take Zyprexa, Zyprexa Relprevv, or Zyprexa Zydis if you are allergic to olanzapine or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

Documented hypersensitivity

Effects of Drug Abuse

No information available

Short-Term Effects

No information available

Long-Term Effects

No information available

Cautions

Increased risk of hyperglycemia and diabetes; in some cases, hyperglycemia concomitant with use of atypical antipsychotics has been associated with ketoacidosis, hyperosmolar coma, or death.

Monitor blood glucose of high-risk patients.

Irreversible, involuntary, dyskinetic movements may develop with antipsychotic drugs; prevalence appears to be highest among elderly individuals, especially elderly women; discontinue if clinically appropriate.

May cause anticholinergic effects including paralytic ileus, urinary retention, xerostomia, BPH, and visual problems.

Neutropenia, leukopenia, and agranulocytosis reported; discontinue therapy at firs sign of blood dyscrasias or if absolute neutrophil count less than 1000/mm³.

Cerebrovascular effects including, stroke and transient ischemic attack resulting in death reported.

NMS has been reported.

Increased potential for weight gain; patients should receive regular monitoring of weight.

Appropriate clinical monitoring is recommended, including fasting blood lipid testing at the beginning of, and periodically during, treatment.

May elevate prolactin levels.

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 properties.

Do not reconstitute with lorazepam injection; do not mix with diazepam or haloperidol in syringe.

FDA warning regarding off-label use for dementia in elderly.

In narrow-angle glaucoma, cardiovascular dis ease, cerebrovascular disease, prostatic hypertrophy, hypovolemia, and dehydration, hyperglycemia may occur and in some cases may be extreme, resulting in ketoacidosis, hyperosmolar coma, or death; IM administration of greater than 1 injection is associated with substantial orthostatic hypotension (33%); maintain patient in recumbent position and monitor blood pressure before repeating IM doses.

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 in patients at risk of pneumonia; may cause esophageal dysmotility and aspiration.

Use caution with strenuous exercise, dehydration, heat exposure, and medications with anticholinergic effects; impaired core body temperature regulation may occur.

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.

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.

Possibility of suicide attempt is inherent in schizophrenia and in 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.

A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) reported; management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; 2) intensive symptomatic treatment and medical monitoring; and 3) treatment of any concomitant serious medical problems for which specific treatments are available; there is no general agreement about specific pharmacological treatment regimens for NMS; if patient requires antipsychotic drug treatment after recovery from NMS, potential reintroduction of drug therapy should be carefully considered; patient should be carefully monitored, since recurrences of NMS reported.

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 (e.g., psychological, educational, social) as well.

IM, extended-release

• Because of risk of post-injection delirium/sedation syndrome, availability is restricted and requires registration (call 877-772-9390).

Pregnancy and Lactation

During pregnancy, use olanzapine with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. Neonates exposed to antipsychotic drugs during 3rd trimester of pregnancy are at risk for extrapyramidal symptoms (EPS) or withdrawal symptoms after delivery; these complications vary in severity, with some being self-limited and others requiring ICU support and prolonged hospitalization.

Olanzapine enters breast milk; it is not recommended for use while breastfeeding.