What is the recommended dosage of Zyprexa (olanzapine) for a patient undergoing chemotherapy to manage nausea and vomiting?

Olanzapine Dosing for Chemotherapy-Induced Nausea and Vomiting

For chemotherapy-induced nausea and vomiting, olanzapine should be dosed at 10 mg orally once daily for days 1-4 when used as part of primary prophylaxis, or 5-10 mg orally daily when used for breakthrough nausea and vomiting. 1

Primary Prophylaxis Dosing (Prevention)

For Highly Emetogenic Chemotherapy (HEC)

• Olanzapine 10 mg orally once daily on days 1-4 in combination with a 5-HT3 antagonist (such as palonosetron), dexamethasone, and optionally an NK1 receptor antagonist 1
• This regimen achieves complete response rates of 80-100% for acute emesis and 80-85% for delayed emesis 2
• The ASCO guidelines specifically recommend this four-drug combination (NK1 antagonist + 5-HT3 antagonist + dexamethasone + olanzapine 10 mg days 1-4) as a category 1 recommendation for patients receiving cisplatin-based chemotherapy 1

For Anthracycline-Cyclophosphamide (AC) Regimens

• Olanzapine 10 mg orally once daily on days 1-4 combined with an NK1 receptor antagonist, 5-HT3 antagonist, and dexamethasone 1
• This is a strong ASCO recommendation specifically for AC combinations, which are commonly used in breast cancer 1

For Moderately Emetogenic Chemotherapy (MEC)

• Olanzapine 10 mg orally once daily on days 1-4 combined with palonosetron and dexamethasone (without NK1 antagonist) is an acceptable alternative regimen 1
• This three-drug combination achieved 85% complete response rates in clinical trials 2

Breakthrough Treatment Dosing

When nausea and vomiting occur despite prophylaxis:

• Olanzapine 5-10 mg orally once daily as a category 1 recommendation 1
• The 5 mg dose is specifically recommended for elderly or over-sedated patients 1
• This should be added as an agent from a different drug class than what the patient is already receiving 1

Dose Adjustment Considerations

Elderly Patients

• Start with 5 mg daily rather than 10 mg due to increased sensitivity to sedation 1
• A randomized phase II study presented at ASCO 2016 suggested that 5 mg may be as effective as 10 mg with less sedation 1

Standard Adult Dosing Schedule

Based on the phase I and II trials that established the current dosing:

• Days -2 and -1 (before chemotherapy): 5 mg orally once daily 3, 2
• Day 0 (day of chemotherapy): 10 mg orally once daily (in addition to IV antiemetics) 3, 2
• Days 1-3 (after chemotherapy): 10 mg orally once daily 3, 2

However, the simplified guideline-recommended approach is 10 mg daily on days 1-4 without the pre-loading doses 1

Important Clinical Considerations

Efficacy Data

• In patients receiving highly emetogenic chemotherapy (cisplatin ≥70 mg/m²), olanzapine achieved 100% complete response for acute emesis and 80% for delayed emesis 2
• For moderately emetogenic chemotherapy (doxorubicin ≥50 mg/m²), complete response was 100% acute and 85% delayed 2
• Nausea control was particularly impressive, with 100% of highly emetogenic chemotherapy patients reporting no nausea in acute and delayed periods 2

Side Effect Profile

• The primary side effect is sedation, which occurred more frequently on day 2 in the pivotal trial 1
• Grade 3 dose-limiting toxicity (depressed level of consciousness) occurred in the phase I trial, establishing 10 mg as the maximum tolerated dose for days 0-7 3
• No grade 4 toxicities were observed in clinical trials 3
• Patients generally did not experience significant drowsiness, dry mouth, mood changes, or restlessness at the recommended doses 2

Common Pitfalls to Avoid

• Do not use olanzapine as monotherapy—it must be combined with other antiemetics (5-HT3 antagonist and dexamethasone at minimum) 1
• Do not exceed 10 mg daily in standard adult patients as higher doses increase sedation without improving efficacy 3
• Do not forget to reduce the dose to 5 mg in elderly patients to minimize sedation risk 1
• Do not discontinue olanzapine after day 1—the full 4-day course is necessary for delayed emesis control 1

Alternative Formulation

• For patients unable to take oral medication, olanzapine can be administered subcutaneously at 10 mg on day 1, followed by oral dosing on subsequent days 4
• This approach was effective and well-tolerated in patients with advanced cancer 4