Is olanzapine (atypical antipsychotic) effective in managing chemotherapy-induced nausea and vomiting (CINV)?

Olanzapine is Effective for Managing Chemotherapy-Induced Nausea and Vomiting (CINV)

Olanzapine is highly effective for both prevention and rescue treatment of chemotherapy-induced nausea and vomiting, particularly for patients receiving highly emetogenic chemotherapy. 1

Mechanism of Action

• Olanzapine is an atypical antipsychotic with unique antiemetic properties due to its ability to antagonize multiple receptors involved in CINV pathways 1
• It targets dopaminergic (D1-D4), serotonergic (5-HT2A, 5-HT2C, 5-HT3, 5-HT6), adrenergic (α1), histaminergic (H1), and muscarinic (m1-m4) receptors 1

Efficacy in CINV Prevention

As Part of Combination Therapy

• In 2017, the NCCN guidelines added a 4-drug regimen including olanzapine as a first-line option (category 1) for highly emetogenic chemotherapy (HEC) 1

• The recommended regimen includes:

  • Olanzapine 10 mg orally once before chemotherapy, then daily for 3 days
  • NK1 receptor antagonist (aprepitant or fosaprepitant)
  • 5-HT3 receptor antagonist
  • Dexamethasone 1

• A phase III randomized trial demonstrated that adding olanzapine to standard antiemetic prophylaxis significantly improved:

  • Complete response rates (no emesis, no rescue medication) during acute (0-24h), delayed (25-120h), and overall (0-120h) phases: 86% vs 65%, 67% vs 52%, and 64% vs 41%, respectively 1
  • No nausea rates during all phases: 74% vs 45%, 42% vs 25%, and 37% vs 22%, respectively 1

• When compared to aprepitant regimens in another phase III trial:

  • Comparable complete response rates for olanzapine (97% acute, 77% delayed/overall) vs aprepitant (87% acute, 73% delayed/overall) 1
  • Superior control of nausea with olanzapine regimen during delayed/overall phases (69% vs 38%) 1

Dosing Considerations

• Standard dose is 10 mg daily for 3-4 days 1
• Lower doses (5 mg) may be considered in elderly or oversedated patients 1, 2
• A meta-analysis showed similar efficacy between 5 mg and 10 mg doses for the no emesis endpoint, with potentially fewer side effects at the lower dose 3

Efficacy for Breakthrough CINV

• NCCN guidelines recommend olanzapine as a category 1 option for breakthrough CINV 1
• A phase III trial comparing olanzapine (10 mg orally 3×/day for 3 days) to metoclopramide for breakthrough CINV showed:
  • Significantly higher rates of no vomiting with olanzapine (70% vs 31%) 1, 4
  • Significantly higher rates of no nausea with olanzapine (68% vs 23%) 1, 4

Safety and Side Effects

• Common side effects are generally mild and include:

  • Somnolence (most common)
  • Postural hypotension
  • Constipation
  • Dizziness
  • Fatigue
  • Dyspepsia 1

• Important safety considerations:

  • Use with caution in elderly patients due to boxed warning regarding increased mortality in elderly patients with dementia-related psychosis 1
  • Avoid concurrent use with other dopamine blockers (metoclopramide, phenothiazines, haloperidol) to prevent excessive dopamine blockade 1
  • Monitor for sedation, which is more pronounced with the 10 mg dose (133% higher than with 5 mg) 2
  • Rare but serious skin reactions (DRESS syndrome) have been reported 1

Clinical Pearls and Caveats

• Olanzapine is used "off-label" for CINV as it is only FDA-approved for psychiatric indications 1
• In some countries, a psychiatrist consultation may be required before prescribing olanzapine 1
• Consider switching to an olanzapine-containing regimen after the first cycle of chemotherapy if patients experience significant emesis despite using other antiemetic regimens 1
• While the NCCN guidelines include olanzapine-containing regimens, other guidelines (MASCC/ESMO and ASCO) have been more cautious about promoting olanzapine for standard antiemetic prophylaxis 1
• Patient selection is crucial when considering olanzapine, taking into account age, comorbidities, and potential drug interactions 1

Conclusion

Olanzapine has demonstrated significant efficacy in both preventing and treating breakthrough CINV, particularly for patients receiving highly emetogenic chemotherapy. Its unique mechanism of targeting multiple receptor types involved in the CINV pathway makes it a valuable addition to standard antiemetic regimens.