OLANZAPINE

brands

Class

• Neuroscience-based Nomenclature: dopamine, serotonin receptor antagonist (DS-RAn)
• Atypical antipsychotic (serotonin– dopamine antagonist; second-generation antipsychotic; also a mood stabilizer)

OLANZAPINE commonly prescribed for

(Bold for FDA approved)

How OLANZAPINE works

• Blocks dopamine 2 receptors, reducing positive symptoms of psychosis and stabilizing affective symptoms

• Blocks serotonin 2A receptors, causing enhancement of dopamine release in certain brain regions and thus reducing motor side effects and possibly improving cognitive and affective symptoms

• Interactions at a myriad of other neurotransmitter receptors may contribute to olanzapine’s efficacy

• Specifically, antagonist actions at serotonin 2C receptors may contribute to efficacy for cognitive and affective symptoms in some patients

• Serotonin 2C antagonist actions plus serotonin reuptake blockade of fluoxetine add to the actions of olanzapine when given as Symbyax (olanzapine–fluoxetine combination)

How long until OLANZAPINE works

• Psychotic and manic symptoms can improve within 1 week, but it may take several weeks for full effect on behavior as well as on cognition and affective stabilization

• Classically recommended to wait at least 4–6 weeks to determine efficacy of drug, but in practice some patients require up to 16–20 weeks to show a good response, especially on negative or cognitive symptoms

• Intramuscular formulation can reduce agitation in 15–30 minutes

Notable Side Effects

• Probably increases risk for diabetes and dyslipidemia

• Dizziness, sedation, weakness

• Dry mouth, constipation, dyspepsia, weight gain

• Peripheral edema

• Joint pain, back pain, chest pain, extremity pain, abnormal gait, ecchymosis

• Tachycardia

• Orthostatic hypotension, usually during initial dose titration

• Tardive dyskinesia (reduced risk compared to conventional antipsychotics)

• Risk of potentially irreversible, involuntary dyskinetic movements may increase with cumulative dose and treatment duration

• Rare rash on exposure to sunlight

Life Threatening Side Effects

• Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients taking atypical antipsychotics

• Rare but serious skin condition known as drug reaction with eosinophilia and systemic symptoms (DRESS)

• Rare neuroleptic malignant syndrome may cause hyperpyrexia, muscle rigidity, delirium, and autonomic instability with elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure

• Rare seizures

• As a class, antipsychotics are associated with an increased risk of death and cerebrovascular events in elderly patients with dementia; not approved for treatment of dementia-related psychosis

• As a class, antidepressants have been reported to increase the risk of suicidal thoughts and behaviors in children and young adults

weight gain

problematic

sedation

common

What to do about OLANZAPINE side effects

• Wait

• Wait

• Wait

• Take at bedtime to help reduce daytime sedation

• Anticholinergics may reduce drug-induced parkinsonism when present

• Beta blockers, benzodiazepines, or serotonin 2A antagonists may reduce akathisia

• Weight loss, exercise programs, and medical management for high BMIs, diabetes, dyslipidemia

• Metformin may help prevent or reverse antipsychotic-induced weight gain

• Switch to another atypical antipsychotic

usual dosage range

• 10–20 mg/day (oral or intramuscular)

• 6–12 mg olanzapine/25–50 mg fluoxetine (olanzapine–fluoxetine combination)

• 150–300 mg/2 weeks or 300–405 mg/4 weeks (see Olanzapine Pamoate after Pearls for dosing and use)

Dosage Forms

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

• Orally disintegrating tablets 5 mg, 10 mg, 15 mg, 20 mg

• Intramuscular formulation 5 mg/mL, each vial contains 10 mg (available in some countries)

• Depot 210 mg, 300 mg, 405 mg

• Olanzapine–fluoxetine combination capsule (mg equivalent olanzapine/mg equivalent fluoxetine) 3 mg/25 mg, 6 mg/25 mg, 6 mg/50 mg, 12 mg/25 mg, 12 mg/50 mg

long term use

• Approved to maintain response in long-term treatment of schizophrenia

• Approved for long-term maintenance in bipolar disorder

• Often used for long-term maintenance in various behavioral disorders

• Should periodically reevaluate long-term usefulness in individual patients, but treatment may need to continue for many years

habit forming

• No

Renal Impairment

• No dose adjustment required for oral formulation

• Not removed by hemodialysis

• For intramuscular formulation, consider lower starting dose (5 mg)

Hepatic Impairment

• May need to lower dose

• Patients with liver disease should have liver function tests a few times a year

• For moderate to severe hepatic impairment, starting oral dose 5 mg; increase with caution

• For intramuscuar formulation, consider lower starting dose (5 mg)

Cardiac Impairment

• Use in patients with cardiac impairment has not been studied, so use with caution because of risk of orthostatic hypotension

• Use with caution if patient is taking concomitant antihypertensive or alpha 1 antagonist

Elderly

• Some patients may tolerate lower doses better

• Increased incidence of stroke

• For intramuscular formulation, recommended starting dose is 2.5–5 mg; a second injection of 2.5–5 mg may be administered 2 hours after first injection; no more than 3 injections should be administered within 24 hours

• Although atypical antipsychotics are commonly used for behavioral disturbances in dementia, no agent has been approved for treatment of elderly patients with behavioral symptoms of dementia such as agitation

• Elderly patients with dementia-related psychosis treated with atypical antipsychotics are at an increased risk of death compared to placebo, and also have an increased risk of cerebrovascular events

• Consider pimavanserin for dementia-related psychosis or Parkinson’s disease psychosis instead of an atypical antipsychotic

Children and Adolescents

• Approved for use in schizophrenia and manic/mixed episodes (ages 13 and older for both)

• Clinical experience and early data suggest olanzapine is probably safe and effective for behavioral disturbances in children and adolescents

• Children and adolescents using olanzapine may need to be monitored more often than adults and may tolerate lower doses better

• Intramuscular formulation has not been studied in patients under 18 and is not recommended for use in this population

Pregnancy

• Controlled studies have not been conducted in pregnant women

• There is a risk of abnormal muscle movements and withdrawal symptoms in newborns whose mothers took an antipsychotic during the third trimester; symptoms may include agitation, abnormally increased or decreased muscle tone, tremor, sleepiness, severe difficulty breathing, and difficulty feeding

• Psychotic symptoms may worsen during pregnancy, and some form of treatment may be necessary

• Early findings of infants exposed to olanzapine in utero currently do not show adverse consequences

• When administered to pregnant rats and rabbits, olanzapine was not teratogenic at doses that are 9- and 30-times the maximum recommended human dose; some fetal toxicities were observed at these doses

• Olanzapine may be preferable to anticonvulsant mood stabilizers if treatment is required during pregnancy

Breast Feeding

• Some drug is found in mother’s breast milk

• There are reports of excess sedation, irritability, poor feeding, and extrapyramidal symptoms (tremors and abnormal muscle movements) in infants exposed to olanzapine through breast milk

• Recommended either to discontinue drug or formula feed

• Infants of women who choose to breast feed while on olanzapine should be monitored for possible adverse effects