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Olanzapine
Aka: Olanzapine, Zyprexa
- Class
- Atypical Antipsychotic (Second Generation agent)
- Neuroleptic
- Thienobenzodiazepine
- Mechanism
- Primarily Serotonin Type II Antagonist (5-HT2 antagonist)
- Also Dopamine, muscarinic Anticholinergic, alpha-1 and histamine H1 antagonist
- Chemical structure similar to Clozapine
- Indications
- Primary Indications
- Schizophrenia
- Acute mania phase of Bipolar Disorder
- Agitated Delirium (emergency department)
- Other Indications
- Migraine Headache
- Appears to have similar efficacy to Droperidol (Inapsine) for Migraine Headache
- Hill (2008) Acad Emerg Med 15(9):806-11 +PMID:19244630 [PubMed]
- Avoid use in Psychosis in Dementia
- Higher risk of CVA and overall mortality in elderly
- Dosing
- Adults
- Start: 5 to 10 mg orally daily
- Increase in 5 mg increments weekly as tolerated
- Maximum: 20 mg/day
- Elderly
- Initial: 1.25 to 2.5 mg PO qd
- Titrate up as tolerated (watch for Hypotension)
- Maximum: 10 mg/day
- Acute management of Agitation
- Dose: 10 mg IM every 4 hours (up to 30 mg/day)
- Emerging: Intravenous dosing
- Only FDA approved for oral and IM delivery
- Large HCMC ED study in 2016 demonstrated safety of IV doses (typically 5 mg)
- No serious complications including no QT Prolongation (although Hypoxia did occur)
- Martel (2016) Acad Emerg Med 23(1): 29-35 +PMID:26720055 [PubMed]
- Adverse Effects
- See Antipsychotics
- Weight gain (4 kg)
- Sedation
- Orthostatic Hypotension
- Seizures (nearly 1% of patients)
- Overall higher mortality in elderly
- Lowest risk of QTc Prolongation compared with other Antipsychotics
- Hyperglycemia
- Increased risk of Diabetes Mellitus
- Koro (2002) BMJ 325:243-5 [PubMed]
- Hyperlipidemia
- Koro (2002) Arch Gen Psychiatry 59:1021-6 [PubMed]
- Other effects
- Neuroleptic malignant sydnrome (rare, but lethal)
- Extrapyramidal Side Effects
- Increased Liver Function Tests
- Increased Creatine Kinase
- Pancreatitis
- Anticholinergic side effects
-
Drug Interactions
- Increase Antipsychotic levels (toxicity risk): Monitor for toxicity
- Ciprofloxacin
- Fluvoxamine
- Decrease Antipsychotic levels (lower efficacy)
- Carbamazepine
- Phenytoin
- Nicotine
- Rifampin
- Omeprazole
- Cardiorespiratory depression (includes sedation, Bradycardia and Hypotension)
- Benzodiazepines (e.g. Midazolam)
- Based on warning in prescribing information since 2005
- Combination appears safe from studies in which Olanzapine was combined with Benzodiazepines
- EMA recommends separating dosing by 60 minutes
- Williams (2018) Ment Health Clin 8(5): 208–213 +PMID: 30206503 [PubMed]
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125121/
- Safety
- Pregnancy Category C
- Not recommended during Lactation (found in Breast Milk)
- Monitoring
- See Antipsychotic
- References
- Glauser and Peters (2016) Crit Dec Emerg Med 30(4): 17-27