Zyprexa (Olanzapine) 80/20 Summary

1. Mechanism & Profile Zyprexa is an atypical antipsychotic used for major psychiatric conditions. Its efficacy stems from dopamine (D1-D4) and serotonin (5-HT2A) receptor antagonism, modulating central activity to treat positive and negative schizophrenia symptoms. It binds 5-HT2C receptors (regulating food intake), explaining notable weight gain. Binding to muscarinic, histamine H-1, and alpha-1 receptors causes somnolence, orthostatic hypotension, and anticholinergic side effects.

2. Key Indications FDA-approved uses:

• Schizophrenia & Bipolar I: Monotherapy or maintenance for manic/mixed episodes.
• Bipolar/Treatment-Resistant Depression: Used jointly with fluoxetine.
• Acute Agitation: Immediate-release IM injections.
• Off-label: Chemotherapy-induced nausea/vomiting (CINV) and PICU delirium.

3. Administration Forms

• Oral: Standard or orally disintegrating tablets; taken without regard to meals.
• Immediate-Release IM: For agitation. Dissolve in sterile water and inject deeply into the gluteal muscle (max 5 mL per site). Peak plasma concentration is 5 times higher than oral.
• Extended-Release IM (Zyprexa Relprevv): Depot injection every 2-4 weeks for schizophrenia maintenance. Provides sustained concentrations; half-life is 30 days.

4. Boxed Warnings

• Post-Injection Delirium/Sedation Syndrome (PDSS): Relprevv carries a strict warning for PDSS if the drug enters the bloodstream rapidly. Must be given in a registered facility. Patients need continuous professional observation for 3+ hours post-injection and an escort home.
• Elderly with Dementia: Increased mortality risk (heart failure, pneumonia) and cerebrovascular events. Not approved for dementia-related psychosis.
• Suicidality: Elevated risk of suicidal thoughts in children and young adults.
• CNS Depression: Impairs cognitive/motor skills, posing a fall risk. Use caution with alcohol/depressants.

5. Pharmacokinetics Extensively metabolized in the liver mainly by CYP1A2, and minimally by CYP2D6. As a major CYP1A2 substrate, concurrent use of inducers (like smoking) increases clearance, requiring dose adjustments. It is 93% protein-bound with an oral half-life of 30 hours. Excreted via urine (57%) and feces (30%).

6. Adverse Reactions Beyond the Boxed Warnings, olanzapine exhibits a wide spectrum of side effects. Common effects involve metabolic disturbances, including hypertriglyceridemia, hypercholesterolemia, hyperglycemia, and increased appetite. Extrapyramidal symptoms, like akathisia and pseudoparkinsonism are also prominent. Severe but rarer reactions include stroke, seizures, neuroleptic malignant syndrome, tardive dyskinesia, and potentially fatal DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms)