What is a recommended antiemetic if Zofran (ondansetron) is not effective?

Recommended Antiemetic When Ondansetron Fails

When ondansetron (Zofran) is not effective, add an agent from a different drug class rather than switching within the same class, with metoclopramide (10-40 mg PO/IV every 4-6 hours), prochlorperazine (10 mg PO/IV every 4-6 hours), or olanzapine (2.5-5 mg PO BID) being the most evidence-based options for breakthrough nausea and vomiting. 1, 2

Algorithmic Approach to Ondansetron Failure

First-Line Breakthrough Options

Add, don't switch: The fundamental principle is to add an agent from a different drug class to the current regimen rather than replacing ondansetron entirely. 1, 2

Phenothiazines (Preferred for most situations):

• Prochlorperazine: 10 mg PO/IV every 4-6 hours, or 25 mg suppository every 12 hours 1
• Promethazine: 12.5-25 mg PO/IV (central line only) every 4 hours 1
• Monitor for dystonic reactions; treat with diphenhydramine 25-50 mg PO/IV every 4-6 hours 1

Metoclopramide (Dopamine antagonist):

• 10-40 mg PO/IV every 4-6 hours 1, 2
• Also requires monitoring for dystonic reactions 1

Second-Line Breakthrough Options

Olanzapine (Atypical antipsychotic - Category 2B):

• 2.5-5 mg PO BID 1, 2
• Note black box warning regarding type II diabetes, hyperglycemia, and death in elderly patients with dementia 1

Haloperidol (Typical antipsychotic):

• 0.5-2 mg PO/IV every 4-6 hours 1

Benzodiazepines (Adjunctive):

• Lorazepam 0.5-2 mg PO/IV every 4-6 hours 1
• Particularly useful for anxiety-related or anticipatory nausea 1, 3

Alternative 5-HT3 Antagonists (If Not Already Tried)

Switch to a different 5-HT3 antagonist:

• Granisetron: 1-2 mg PO daily or 1 mg PO BID, or 0.01 mg/kg IV (maximum 1 mg) 1
• Dolasetron: 100 mg PO daily (note: IV formulation withdrawn due to cardiac safety concerns) 1, 3
• Palonosetron (preferred): 0.25 mg IV or 0.50 mg PO - superior efficacy for both acute and delayed nausea/vomiting 1, 2, 3

Corticosteroids (If Not Already Included)

Dexamethasone:

• 12 mg PO/IV daily 1, 2
• Enhances efficacy when combined with 5-HT3 antagonists 1, 4, 5

Third-Line Options

Cannabinoids:

• Dronabinol 5-10 mg PO every 3-6 hours 1
• Nabilone 1-2 mg PO BID 1

Scopolamine:

• 1 patch every 72 hours 1

Critical Management Principles

Switch to scheduled dosing: Once breakthrough nausea/vomiting occurs, continue medications on a controlled schedule rather than PRN. 1, 2

Escalate for next cycle: Consider changing antiemetic therapy to a higher level of primary treatment for the next chemotherapy cycle if breakthrough occurs. 1

Reevaluate underlying cause: Consider dose adjustments of the antiemetic regimen and/or switching to different therapy if nausea/vomiting persists. 1

Common Pitfalls to Avoid

Extrapyramidal symptoms: Both metoclopramide and prochlorperazine carry risk of dystonic reactions - have diphenhydramine readily available (or benztropine if diphenhydramine allergy). 1, 2

Inadequate prophylaxis: Ondansetron failure often reflects inadequate initial prophylaxis rather than true drug failure - ensure appropriate combination therapy (5-HT3 antagonist + dexamethasone ± NK1 antagonist) was used initially. 1, 2

Delayed emesis: Ondansetron alone is less effective for delayed emesis (days 2-5) - this may require addition of dexamethasone, aprepitant, or metoclopramide rather than indicating ondansetron failure. 1, 2

Cardiac considerations: Avoid IV dolasetron due to cardiac safety concerns; use oral formulation only. 3