What is the next antiemetic to consider for persistent vomiting in a patient already on ondansetron (Zofran)?

Next Antiemetic Options After Ondansetron for Persistent Vomiting

For persistent vomiting in a patient already on ondansetron, add a dopamine receptor antagonist such as prochlorperazine, haloperidol, or metoclopramide as the next antiemetic agent. 1

Stepwise Approach for Managing Persistent Vomiting

First-Line Addition (After Ondansetron)

• Add a dopamine receptor antagonist, which works through a different mechanism than ondansetron (5-HT3 antagonist) 1
  • Prochlorperazine 10 mg PO/IV every 6 hours as needed (preferred due to less sedation) 2
  • Haloperidol 0.5-2 mg PO/IV every 4-6 hours 1
  • Metoclopramide 10-40 mg PO/IV every 4-6 hours (has additional prokinetic effects) 1
  • Olanzapine 2.5-5 mg PO twice daily 1

Second-Line Options (If Vomiting Persists)

• Add an anticholinergic agent (e.g., scopolamine patch every 72 hours) 1
• Add an antihistamine (e.g., meclizine) 1
• Add a cannabinoid (e.g., dronabinol 5-10 mg PO every 3-6 hours) 1

Third-Line Options

• Add a corticosteroid (e.g., dexamethasone 4-8 mg daily) 1
• Consider continuous IV/subcutaneous infusion of antiemetics for intractable vomiting 1

Special Considerations

Underlying Causes to Address

• Rule out constipation or fecal impaction as a cause of persistent nausea and vomiting 1
• Consider gastroparesis (metoclopramide 5-10 mg PO QID 30 min before meals may help) 1
• Evaluate for bowel obstruction, which requires specific management 1
• If opioid-induced, consider opioid rotation 1

Medication Selection Based on Patient Factors

• For patients with anxiety contributing to nausea/vomiting, consider adding lorazepam 0.5-1 mg every 4 hours 1
• For patients with constipation, metoclopramide may be particularly beneficial due to its prokinetic effects 2
• Monitor for extrapyramidal symptoms with dopamine antagonists; have diphenhydramine 25-50 mg available for treatment 2

Evidence Quality and Considerations

The NCCN guidelines provide a clear algorithm for managing persistent nausea and vomiting, recommending the addition of agents with different mechanisms of action when ondansetron alone is insufficient 1. The guidelines specifically recommend dopamine receptor antagonists as the next step after 5-HT3 antagonists like ondansetron 1.

Prochlorperazine is often preferred over promethazine due to its effectiveness and lower sedation profile 2. For patients with both nausea and constipation, metoclopramide offers the advantage of prokinetic effects 2.

While combination therapy is often necessary for persistent symptoms, it's important to monitor for potential drug interactions and cumulative side effects when using multiple antiemetics 1.