Olanzapine

Aka: Olanzapine, Zyprexa, Lybalvi

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II. Class

  1. Atypical Antipsychotic (Second Generation agent)
  2. Neuroleptic
  3. Thienobenzodiazepine

III. 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

IV. Indications

  1. Primary Indications
    1. Schizophrenia
    2. Acute mania phase of Bipolar Disorder
    3. Agitated Delirium (emergency department)
    4. Bipolar Depression
      1. Combine with Fluoxetine or other Antidepressant
  2. Other Indications
    1. Obsessive Compulsive Disorder
      1. Combine with Antidepressant (esp. SSRI)
    2. Acute 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

V. 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

VI. Dosing: Schizophrenia, Bipolar Disorder

  1. Adult Oral Dosing
    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 Oral Dosing
    1. Initial: 1.25 to 2.5 mg orally daily
    2. Titrate up as tolerated (watch for Hypotension)
    3. Maximum: 10 mg/day
  3. Child Oral Dosing (age 13 to 17 years old)
    1. Start 2.5 to 5 mg orally daily
    2. May increase by 2.5 to 5 mg/day to target dose of 10 mg orally daily
    3. Maximum: 20 mg/day
  4. Adult Long Acting Intramuscular Injection
    1. Olanzapine XR 150 to 300 mg deep gluteal IM every 2 weeks (or 300 to 405 mg deep IM every 4 weeks)
    2. Base dose on prior oral dosing

VII. Dosing: Acute Agitation

  1. Acute management of Agitation (Psychosis, acute bipolar mania or Schizophrenia)
    1. Dose: 10 mg IM every 4 hours (up to 30 mg/day)
    2. Dosing schedule may also be increased (maximum total 30 mg/day)
      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)
  2. 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]

VIII. Adverse Effects

  1. See Antipsychotics
  2. Weight gain (4 kg)
  3. Sedation
  4. Headache
  5. Orthostatic Hypotension (21% with oral dosing, even higher risk with IM 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. Bradycardia, Hypotension and hypoventilation may occur with IM dosing (esp. when combined with Benzodiazepines)
  13. Hyperglycemia
    1. Increased risk of Diabetes Mellitus
    2. Koro (2002) BMJ 325:243-5 [PubMed]
  14. Hyperlipidemia
    1. Koro (2002) Arch Gen Psychiatry 59:1021-6 [PubMed]
  15. 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)

IX. 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/

X. Safety

  1. Pregnancy Category C
    1. However, does cross placenta
  2. Not recommended during Lactation (found in Breast Milk)

XI. Monitoring

  1. See Antipsychotic

XII. Resources

  1. Olanzapine (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=6a5db723-0f21-417e-a95c-cf0c438e8b44

XIII. References

  1. (2016) Med Lett Drugs Ther 58(1510): 160-5
  2. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 42-3
  3. Hamilton (2020) Tarascon Pocket Pharmacopoeia
  4. Glauser and Peters (2016) Crit Dec Emerg Med 30(4): 17-27
  5. LoVecchio (2021) Crit Dec Emerg Med 35(9): 31

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Related Studies

Cost: Medications

olanzapine (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
OLANZAPINE 10 MG TABLET Generic $0.11 each
OLANZAPINE 15 MG TABLET Generic $0.15 each
OLANZAPINE 2.5 MG TABLET Generic $0.08 each
OLANZAPINE 20 MG TABLET Generic $0.18 each
OLANZAPINE 5 MG TABLET Generic $0.09 each
OLANZAPINE 7.5 MG TABLET Generic $0.12 each
OLANZAPINE ODT 10 MG TABLET Generic $0.41 each
OLANZAPINE ODT 15 MG TABLET Generic $0.80 each
OLANZAPINE ODT 20 MG TABLET Generic $0.82 each
OLANZAPINE ODT 5 MG TABLET Generic $0.50 each
OLANZAPINE-FLUOXETINE 12-50 MG Generic $8.49 each
OLANZAPINE-FLUOXETINE 3-25 MG Generic $4.79 each
OLANZAPINE-FLUOXETINE 6-25 MG Generic $4.20 each
OLANZAPINE-FLUOXETINE 6-50 MG Generic $5.95 each
zyprexa (on 1/1/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
ZYPREXA 10 MG TABLET Generic $0.11 each
ZYPREXA 15 MG TABLET Generic $0.15 each
ZYPREXA 20 MG TABLET Generic $0.18 each
lybalvi (on 11/15/2023 at Medicaid.Gov Survey of pharmacy drug pricing)
LYBALVI 10-10 MG TABLET $48.23 each
LYBALVI 15-10 MG TABLET $48.17 each
LYBALVI 20-10 MG TABLET $48.24 each
LYBALVI 5-10 MG TABLET $48.34 each
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information. GoodRx is another tool for finding lower drug prices.

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