Olanzapine

# Olanzapine ## Overview - **Classification**: Atypical antipsychotic (second-generation antipsychotic) - **Mechanism**: Antagonizes dopamine D2 and serotonin 5-HT2A receptors, also binds to muscarinic, histamine H1, and alpha-1 adrenergic receptors. ## Primary Indications 1. **Schizophrenia** - Acute and maintenance treatment. 2. **Bipolar I Disorder** - Acute manic or mixed episodes (monotherapy or adjunctive), maintenance treatment. 3. **Depression, Treatment-Resistant** - Adjunctive therapy with fluoxetine. 4. **Agitation** - Associated with schizophrenia or bipolar mania (IM formulation). ## Adult Dosing ### Standard Dosing **Schizophrenia** (Oral) - **Initial Dose**: **5-10 mg** once daily - **Target Dose**: **10 mg** once daily - **Frequency**: Once daily - **Route**: Oral - **Maximum Dose**: **20 mg** per day **Bipolar I Disorder - Acute Manic or Mixed Episodes** (Oral) - **Monotherapy Initial Dose**: **10-15 mg** once daily - **Adjunctive with Lithium/Valproate Initial Dose**: **10 mg** once daily - **Frequency**: Once daily - **Route**: Oral - **Maximum Dose**: **20 mg** per day **Bipolar I Disorder - Maintenance** (Oral) - **Dose**: **5-20 mg** once daily - **Frequency**: Once daily - **Route**: Oral **Treatment-Resistant Depression (Adjunctive with Fluoxetine)** (Oral) - **Initial Dose**: Olanzapine **5 mg** once daily + Fluoxetine **20 mg** once daily - **Target Dose**: Olanzapine **6-12 mg** once daily + Fluoxetine **25-50 mg** once daily - **Frequency**: Once daily - **Route**: Oral - **Maximum Dose**: Olanzapine **18 mg** + Fluoxetine **75 mg** per day **Agitation Associated with Schizophrenia or Bipolar Mania** (Intramuscular) - **Initial Dose**: **10 mg** IM - **Frequency**: May give a second injection of **5-10 mg** after 2 hours. - **Route**: Intramuscular (IM) - **Maximum Dose**: **30 mg** per 24 hours (including any oral olanzapine). ### Dose Adjustments - **Renal Impairment**: No specific dose adjustment recommended. - **Hepatic Impairment**: Consider starting at **5 mg** once daily. - **Elderly Patients**: Consider starting at **5 mg** once daily. Increased risk of orthostatic hypotension. ## Pediatric Dosing ### Neonates (0-28 days) - **Special Notes**: Not FDA approved for this age group. Use generally discouraged due to safety and efficacy concerns. ### Infants (1-12 months) - **Special Notes**: Not FDA approved for this age group. Use generally discouraged due to safety and efficacy concerns. ### Children (1-12 years) - **Special Notes**: Not FDA approved for this age group for schizophrenia or bipolar disorder. Generally not recommended due to lack of data and higher risk of metabolic side effects. ### Adolescents (13-17 years) **Schizophrenia** (Oral) - **Initial Dose**: **2.5-5 mg** once daily - **Target Dose**: **10 mg** once daily - **Frequency**: Once daily - **Route**: Oral - **Maximum Dose**: **20 mg** per day - **Special Notes**: Higher rates of weight gain, dyslipidemia, and elevated prolactin compared to adults. **Bipolar I Disorder - Acute Manic or Mixed Episodes** (Oral) - **Initial Dose**: **2.5-5 mg** once daily - **Target Dose**: **10 mg** once daily - **Frequency**: Once daily - **Route**: Oral - **Maximum Dose**: **20 mg** per day - **Special Notes**: Monitor for significant metabolic changes closely. ## Safety Information ### Contraindications - **Absolute**: Hypersensitivity to olanzapine. - **Absolute**: Concurrent use with benzodiazepines for IM formulation due to cardiorespiratory depression (particularly with IV diazepam). - **Relative**: Narrow-angle glaucoma (use with caution). - **Black Box Warning**: Increased mortality in elderly patients with dementia-related psychosis. Olanzapine is not approved for this indication. ### Common Adverse Effects - **Very Common (>10%)**: Somnolence, weight gain, dry mouth, increased appetite, dizziness, orthostatic hypotension. - **Common (1-10%)**: Constipation, peripheral edema, tremor, akathisia, asthenia, increased prolactin, hyperglycemia, dyslipidemia, blurred vision. - **Serious but Rare**: Neuroleptic Malignant Syndrome (NMS), Tardive Dyskinesia (TD), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), seizures, agranulocytosis, severe hepatotoxicity, cerebrovascular adverse events (in elderly dementia patients), severe cutaneous reactions, QT prolongation. ### Key Drug Interactions - **CYP1A2 Inhibitors (e.g., Fluvoxamine, Ciprofloxacin)**: May increase olanzapine levels. Consider lower olanzapine dose. - **CYP1A2 Inducers (e.g., Carbamazepine, Rifampin, Tobacco Smoke)**: May decrease olanzapine levels. Consider increasing olanzapine dose. - **CNS Depressants (e.g., Benzodiazepines, Alcohol)**: Additive CNS depression. Avoid concurrent use, especially with IM olanzapine. - **Anticholinergics**: Potentiates anticholinergic effects (e.g., dry mouth, constipation). - **Antihypertensives**: Increased risk of orthostatic hypotension. Monitor blood pressure. ## Monitoring & Follow-up - **Before Treatment**: Baseline weight, BMI, waist circumference, blood pressure, fasting glucose, HbA1c, fasting lipid profile, LFTs. - **During Treatment**: - **Weight/BMI**: Weekly for 1 month, then monthly. - **Glucose/HbA1c**: At 3 months, then annually. - **Lipids**: At 3 months, then every 5 years (more frequently if risk factors present). - **Blood Pressure**: At baseline and periodically. - **EPS/TD**: Screen regularly with AIMS scale. - **Clinical Signs**: Monitor for NMS (fever, rigidity, altered mental status), suicidal ideation, and agranulocytosis. ## Clinical Pearls - 💡 **Metabolic Risk**: Olanzapine carries a high risk of weight gain, hyperglycemia, and dyslipidemia. Emphasize lifestyle interventions. - 💡 **Sedation**: Dose-related sedation is common, often improves over time. Consider bedtime dosing. - 💡 **Orthostatic Hypotension**: Warn patients about dizziness upon standing, especially with initial dosing. - 💡 **ODT Formulation**: Orally disintegrating tablets (ODT) can be used without water, useful for patients with swallowing difficulties or adherence concerns. - 💡 **Smoking**: Smoking induces CYP1A2, reducing olanzapine levels. Dose adjustments may be needed if smoking status changes. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.