Second-Line Antiemetic Medication Options
Olanzapine is the recommended first-choice second-line antiemetic medication for patients experiencing breakthrough nausea and vomiting despite optimal prophylaxis. 1
First-Line Failure Management Algorithm
When first-line antiemetics fail to control nausea and vomiting, follow this evidence-based approach:
Step 1: Add Olanzapine (Category 1 recommendation)
- Dosage: 5-10 mg PO daily 1
- Evidence: Superior to metoclopramide for breakthrough nausea/vomiting with 70% vs 31% emesis control and 68% vs 23% nausea control 1
- Caution: Consider 5 mg dose for elderly or those experiencing sedation 1
- Contraindication: If already receiving olanzapine as part of prophylactic regimen
Step 2: If Olanzapine Already Used or Contraindicated, Add One Agent from a Different Class:
NK1 Receptor Antagonists
- Options: Aprepitant, fosaprepitant, rolapitant 1
- Mechanism: Block substance P from binding to NK1 receptors
- Note: Particularly effective when combined with 5-HT3 antagonists and dexamethasone
Benzodiazepines
- Options: Lorazepam 0.5-2 mg PO/SL/IV every 6h or alprazolam 1
- Benefit: Helps with anxiety component of nausea and works synergistically
Dopamine Receptor Antagonists
- Options:
- Metoclopramide 10-20 mg PO/IV every 4-6h
- Prochlorperazine 10 mg PO/IV every 6h or 25 mg suppository every 12h
- Haloperidol 0.5-2 mg PO/IV every 4-6h 1
- Caution: Monitor for extrapyramidal symptoms
Cannabinoids
- Options:
- Dronabinol 5-10 mg PO every 4-6h
- Nabilone 1-2 mg PO BID 1
- Evidence: Intermediate quality evidence for efficacy 1
Other Options
- Scopolamine: 1.5 mg transdermal patch every 72h 1
- Dexamethasone: 12 mg PO/IV daily (if not already using) 1, 2
Special Populations Considerations
Elderly Patients
- Start with lower doses of all agents
- Olanzapine: Use with caution; consider 2.5 mg dose due to risk of sedation and increased mortality in dementia patients 3
- Preferred options: Ondansetron, haloperidol (low dose), or prochlorperazine 3
- Monitor: Sedation, extrapyramidal symptoms, QT prolongation
Chemotherapy-Induced Nausea and Vomiting
- For high-emetic-risk chemotherapy: Consider escalating to 4-drug regimen (NK1 antagonist + 5-HT3 antagonist + dexamethasone + olanzapine) 1, 4
- For moderate-emetic-risk: Consider adding NK1 antagonist if not already included 1
Radiation-Induced Nausea and Vomiting
- For high-emetic-risk radiation: Use 5-HT3 antagonist plus dexamethasone 1
- For moderate-emetic-risk radiation: Use 5-HT3 antagonist with or without dexamethasone 1
Clinical Pearls and Pitfalls
Important Considerations
- Re-evaluate: Before adding second-line agents, reassess emetic risk, disease status, concurrent illnesses, and medications 1
- Schedule vs PRN: Continue breakthrough medications on a schedule rather than PRN for better control 1
- Next cycle planning: Consider changing antiemetic therapy to higher level primary treatment for next chemotherapy cycle 1
Potential Pitfalls
- QT prolongation: Monitor when using 5-HT3 antagonists (ondansetron) or certain dopamine antagonists 5
- Drug interactions: Avoid combining olanzapine with other dopamine blockers (metoclopramide, phenothiazines, haloperidol) due to risk of excessive dopamine blockade 1
- Sedation: Major concern with olanzapine; monitor closely, especially in elderly 1, 4
Evidence Quality Assessment
The recommendation for olanzapine as first-choice second-line therapy is based on high-quality evidence, including a randomized controlled trial showing superior efficacy compared to metoclopramide 1. The NCCN guidelines have upgraded olanzapine for breakthrough emesis to category 1 (from category 2A) based on the magnitude of superiority shown in this double-blind, randomized, prospective trial 1.
For other second-line agents, the evidence quality ranges from intermediate (for cannabinoids) to low (for other agents) 1, but the benefits generally outweigh the harms when used appropriately.