Olanzapine

Aka: Olanzapine, Zyprexa, Lybalvi

1. See Also
   1. Antipsychotic Medication
   2. Psychosis
2. Class
   1. Atypical Antipsychotic (Second Generation agent)
   2. Neuroleptic
   3. Thienobenzodiazepine
3. Mechanism
   1. Primarily Serotonin Type II Antagonist (5-HT2 antagonist - 5-HT2A and 5-HT2C, as well as 5-HT3)
   2. Also Dopamine (D1-4), muscarinic (M1-5) Anticholinergic, adrenergic (alpha-1) and histamine (H1) antagonist
   3. Chemical structure similar to Clozapine
4. Indications
   1. Primary Indications
      1. Schizophrenia
      2. Acute mania phase of Bipolar Disorder
      3. Agitated Delirium (emergency department)
   2. Other Indications
      1. Migraine Headache
         1. Appears to have similar efficacy to Droperidol (Inapsine) for Migraine Headache
         2. Hill (2008) Acad Emerg Med 15(9):806-11 +PMID:19244630 [PubMed]
   3. Avoid use in Psychosis in Dementia
      1. Higher risk of CVA and overall mortality in elderly
5. Preparations
   1. Olanzapine (Zyprexa)
      1. Standard preparation, and generic ($30/month)
   2. Olanzapine/Samidorphan (Lybalvi)
      1. Released in 2021 at $1400/month
      2. Samidorphan is a Naltrexone derivative added to reduce weight gain that typically occurs with Olanzapine
      3. Avoid all Opioids while on Samidorphan (and causes withdrawal in those on Chronic Opioids)
         1. Transition to Olanzapine without Samidorphan at least 5 days before Opioid management needed
      4. Marginal efficacy for cost (other strategies to reduce weight gain are preferred)
         1. Consider Antipsychotics less associated with weight gain (e.g. Aripiprazole, Ziprasidone)
         2. Lifestyle changes (Exercise and diet)
         3. Consider Metformin
      5. References
         1. (2022) Presc Lett 29(1): 6
6. Dosing
   1. Adults
      1. Start: 5 to 10 mg orally daily (may be repeated every 2 hours to total maximum of 20 mg/day)
      2. Increase in 5 mg increments weekly as tolerated
      3. Maximum: 20 mg/day
   2. Elderly
      1. Initial: 1.25 to 2.5 mg orally daily
      2. Titrate up as tolerated (watch for Hypotension)
      3. Maximum: 10 mg/day
   3. Acute management of Agitation
      1. Dose: 10 mg IM every 4 hours (up to 30 mg/day)
      2. Dosing schedule may also be increased
         1. Dose 1 at time 0 hours: 10 mg
         2. Dose 2 at time 2 hours: 10 mg
         3. Dose 3 at time 6 hours: 10 mg (last dose for day)
   4. Emerging: Intravenous dosing in Agitation
      1. Off label use (Only FDA approved for oral and IM delivery)
      2. Use only in closely monitored settings (respiratory depression, Hypotension)
      3. Initial Dose: 5 mg IV
      4. Subsequent dose: 2.5 to 5 mg IV at least 10 minutes after initial dose (maximum 10 mg/day)
      5. Large HCMC ED study in 2016 demonstrated safety of 5 mg IV doses
         1. No serious complications including no QT Prolongation (although Hypoxia did occur)
         2. Martel (2016) Acad Emerg Med 23(1): 29-35 +PMID:26720055 [PubMed]
7. Adverse Effects
   1. See Antipsychotics
   2. Weight gain (4 kg)
   3. Sedation
   4. Headache
   5. Orthostatic Hypotension (21% with oral dosing)
   6. Seizures (nearly 1% of patients)
   7. Extrapyramidal Side Effects
   8. Akathisia (27%)
   9. Cognitive slowing
   10. Overall higher mortality in elderly (see Atypical Antipsychotics)
   11. Lowest risk of QTc Prolongation compared with other Antipsychotics
   12. Hyperglycemia
       1. Increased risk of Diabetes Mellitus
       2. Koro (2002) BMJ 325:243-5 [PubMed]
   13. Hyperlipidemia
       1. Koro (2002) Arch Gen Psychiatry 59:1021-6 [PubMed]
   14. Other effects
       1. Neuroleptic malignant sydnrome (rare, but lethal)
       2. Increased Liver Function Tests
       3. Increased Creatine Kinase
       4. Pancreatitis
       5. Anticholinergic side effects
       6. Hyperprolactinemia (secondary reproductive function disorders)
8. Drug Interactions
   1. Increase Antipsychotic levels (toxicity risk): Monitor for toxicity
      1. Ciprofloxacin
      2. Fluvoxamine
   2. Decrease Antipsychotic levels (lower efficacy)
      1. Carbamazepine
      2. Phenytoin
      3. Nicotine
      4. Rifampin
      5. Omeprazole
   3. Cardiorespiratory depression (includes sedation, Bradycardia and Hypotension)
      1. Benzodiazepines (e.g. Midazolam)
         1. Based on warning in prescribing information since 2005
         2. Combination appears safe from studies in which Olanzapine was combined with Benzodiazepines
         3. EMA recommends separating dosing by 60 minutes
         4. Williams (2018) Ment Health Clin 8(5): 208–213 +PMID: 30206503 [PubMed]
            1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125121/
9. Safety
   1. Pregnancy Category C
      1. However, does cross placenta
   2. Not recommended during Lactation (found in Breast Milk)
10. Monitoring
    1. See Antipsychotic
11. References
    1. Glauser and Peters (2016) Crit Dec Emerg Med 30(4): 17-27
    2. LoVecchio (2021) Crit Dec Emerg Med 35(9): 31