Olanzapine (Zyprexa) in Chemotherapy Induced Nausea and Vomiting

Written by Julianne Orr, PharmD, Indiana University Health Simon Cancer Center
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Olanzapine (Zyprexa) is an FDA approved atypical antipsychotic that blocks multiple neuronal receptors involved in nausea/vomiting pathways.  This PQI will review the appropriate use of olanzapine for prevention and treatment of CINV.


Historically, patients have been prescribed dexamethasone along with a 5HT3 antagonist (ex. ondansetron) to prevent nausea and vomiting. For patients receiving highly and often moderately emetogenic chemotherapy, and NK1 receptor antagonist, such as fosaprepitant, is added to the antiemesis regimen. Olanzapine has been studied for breakthrough2 CINV as well as prophylaxis of highly and moderately emetogenic regimens3,4,5.  Additionally, olanzapine has been studied in replacement of NK1 receptor antagonists (i.e., aprepitant) as well as in addition to standard triplet prophylaxis regimens which include NK1 receptor antagonists4,5,6,7. The results of these trials suggest olanzapine is at least as effective as aprepitant and combination olanzapine with aprepitant has led to promising reports of CINV control. Based on the results from these various studies, Clinically, lower doses of 5mg and 2.5mg have been used in patients where sedation may be a concern.

PQI Process

Upon receipt of an order for a HEC or MEC chemotherapy regimen:

  • Screen for appropriate antiemesis medications:  
    • Dexamethasone
    • 5HT3 Antagonist
    • NK1 Antagonist
    • +/- Olanzapine
  • If olanzapine if not initially included in the orders, consider recommending the addition of olanzapine 5-10mg PO daily Days 1 through 4 of chemotherapy.
  • If the patient is elderly or over-sedated, consider using a lower dose upon initiation8.
  • Use caution when prescribing olanzapine with metoclopramide or haloperidol, as this combination may lead to a higher risk of extrapyramidal symptoms.  

Patient Centered Activities

  • Patient Complianceo Encourage patients to take this medication each day, as prescribedo This is particularly important for any patients receiving HEC or MEC regimens in the outpatient setting
  • Patient Education
    • Explain CINV and the different medications that are being prescribed to help prevent nausea and vomiting
    • Outline the reason patients take olanzapine on days 1 through 4 only* *some multiple day HEC regimens may require more than 4 days of therapy
    • Olanzapine may be administered without regard to meals
    • Review common side effects with the patient
      • Drowsiness
      • Headache
      • Disturbed sleep
      • Extrapyramidal reactions
      • Increased appetite
      • Constipation
    • Drowsiness will potentially diminish over time



  1. Tan L, Liu J, Liu X, et al. Clinical research of olanzapine for prevention of chemotherapy induced nausea and vomiting. J Exp Clin Cancer Res 2009; 28: 1-7.
  2. Navari RM, Nagy CK, Gray SE. The use of olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy induced nausea and vomiting in patients receiving highly emetogenic chemotherapy. Support Care Cancer 2013; 21: 1655-63.
  3. Navari RM, Gray SE, Kerr AC. Olanzapine versus aprepitant for the prevention of chemotherapy induced nausea and vomiting: a randomized phase 3 trial. J Support Oncol 2011; 9: 188-95.
  4. Mizukami N, Yamauchi, Koike K, et al. Olanzapine for the prevention of chemotherapy induced nausea and vomiting in patients receiving highly or moderately emetogenic chemotherapy: a randomized, double blinded, placebo controlled study. J Pain Symptom Manage 2014; 47: 542-50.
  5. Abe M, Hirashima Y, Kasamatsu Y, et al. Efficacy and safety of olanzapine combined with aprepitant, palonosetron, and dexamethasone for preventing nausea and vomiting induced by cisplatin based chemotherapy in gynecological cancer. Support Care Cancer. E-pub ahead of print: 01 July 2015. DOI: 10.1007/s00520-015-2829-z
  6. Passik SD, Navari RM, Jung S, et al. Phase I trial of olanzapine for the prevention of delayed emesis in cancer patients: A Hoosier Oncology Group study. Cancer Investigations 2004; 22(3): 383-388.
  7. Navari A phase II trial of olanzapine, dexamethasone,and palonosetron for the prevention of chemotherapy induced nausea and vomiting: a Hoosier oncology group study. Support Care Cancer 2007; 15:1285–1291
  8. Hashimoto H, Yanai T, Nagashima K, et al. A double blind randomized phase II study of 10 versus 5mg olanzapine for emesis induced by highly emetogenic chemotherapy with cisplatin [abstract]. J Clin Oncol 2016; 34: Abstr 10111.

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