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Olanzapine

Aka: Olanzapine, Zyprexa
  1. Class
    1. Atypical Antipsychotic (Second Generation agent)
    2. Neuroleptic
    3. Thienobenzodiazepine
  2. 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
  3. 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
  4. 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]
  5. 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)
  6. 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/
  7. Safety
    1. Pregnancy Category C
      1. However, does cross placenta
    2. Not recommended during Lactation (found in Breast Milk)
  8. Monitoring
    1. See Antipsychotic
  9. References
    1. Glauser and Peters (2016) Crit Dec Emerg Med 30(4): 17-27
    2. LoVecchio (2021) Crit Dec Emerg Med 35(9): 31
Medication Costs
olanzapine (on 5/17/2017 at Medicaid.Gov Pharmacy Drug pricing)
OLANZAPINE 10 MG TABLET Generic $0.19 each
OLANZAPINE 15 MG TABLET Generic $0.31 each
OLANZAPINE 2.5 MG TABLET Generic $0.13 each
OLANZAPINE 20 MG TABLET Generic $0.34 each
OLANZAPINE 5 MG TABLET Generic $0.14 each
OLANZAPINE 7.5 MG TABLET Generic $0.18 each
OLANZAPINE ODT 10 MG TABLET Generic $1.38 each
OLANZAPINE ODT 15 MG TABLET Generic $1.44 each
OLANZAPINE ODT 20 MG TABLET Generic $2.63 each
OLANZAPINE ODT 5 MG TABLET Generic $1.31 each
OLANZAPINE-FLUOXETINE 12-25 MG Generic $13.13 each
OLANZAPINE-FLUOXETINE 12-50 MG Generic $14.19 each
OLANZAPINE-FLUOXETINE 3-25 MG Generic $7.23 each
OLANZAPINE-FLUOXETINE 6-25 MG Generic $7.95 each
OLANZAPINE-FLUOXETINE 6-50 MG Generic $9.74 each
zyprexa (on 6/22/2016 at Medicaid.Gov Pharmacy Drug pricing)
ZYPREXA ZYDIS 10 MG TABLET Generic $1.38 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.

olanzapine (C0171023)

Definition (CHV) a drug used to treat schizophrenia
Definition (NCI_NCI-GLOSS) A drug used to treat certain mental disorders. It is also being studied in the treatment of nausea and vomiting caused by some cancer treatments. It is a type of antipsychotic and a type of monoamine antagonist.
Definition (NCI) A synthetic derivative of thienobenzodiazepine with antipsychotic, antinausea, and antiemetic activities. As a selective monoaminergic antagonist, olanzapine binds with high affinity binding to the following receptors: serotoninergic, dopaminergic, muscarinic M1-5, histamine H1, and alpha-1-adrenergic receptors; it binds weakly to gamma-aminobutyric acid type A, benzodiazepine, and beta-adrenergic receptors. The antinausea and antiemetic effects of this agent appear to be due to the blockade of 5-HT2 and 5-HT3 receptors for serotonin. Although its exact mechanism of action in schizophrenia is unknown, it has been proposed that olanzapine's antipsychotic activity is mediated through antagonism to dopamine D2 receptors with rapid ligand-receptor dissociation kinetics that help to minimize extrapyramidal symptoms (EPS). Olanzapine may also stimulate appetite.
Definition (PDQ) A synthetic derivative of thienobenzodiazepine with antipsychotic properties. As a selective monoaminergic antagonist, olanzapine binds with high affinity binding to the following receptors: serotonin, dopamine, muscarinic M1-5, histamine H1, and alpha1-adrenergic receptors; it binds weakly to gamma-aminobutyric acid type A, benzodiazepine, and beta-adrenergic receptors. Although its exact mechanism of action in schizophrenia is unknown, it has been proposed that olanzapine's antipsychotic activity is mediated through a combination of dopamine and serotonin type 2 antagonism. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=449664&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=449664&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C47639" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C076029
SnomedCT 108441004, 386849001
LNC LP18087-4, MTHU002999
English 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno(2,3-b)(1,5)benzodiazepine, olanzapine, 2-Methyl-4-(4-methyl-1-piperazinyl)-10H-thieno(2,3-b)(1,5)benzodiazepine, olanzapine (medication), olanzapine [Chemical/Ingredient], OLANZAPINE, olanzapine (Zyprexa), OLANZapine, Olanzapine, Olanzapine (product), Olanzapine (substance)
Spanish olanzapina (producto), olanzapina (sustancia), olanzapina
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Zyprexa (C0527258)

Definition (CHV) a kind of psychiatry drug
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C076029
English Zyprexa, zyprexa, ZyPREXA, Eli Lilly brand of olanzapine, Lilly brand of olanzapine
Sources
Derived from the NIH UMLS (Unified Medical Language System)


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