What is the next step for patients with cyclical vomiting syndrome who do not respond to Zofran (ondansetron)?

Next Steps for Patients with Cyclical Vomiting Syndrome Who Do Not Respond to Ondansetron

For patients with cyclical vomiting syndrome who do not respond to ondansetron, the next step should be to try a neurokinin-1 (NK-1) receptor antagonist such as aprepitant, which has shown dramatic response in refractory cases.

Medication Options After Ondansetron Failure

First-Line Alternative: NK-1 Receptor Antagonists

• Aprepitant:
  • Dosing: 125 mg on day 1, followed by 80 mg on days 2 and 3 1
  • Mechanism: Blocks substance P in critical areas involved in nausea and vomiting
  • Evidence: Has shown dramatic response in severe CVS cases that failed ondansetron therapy 2
  • Can be administered at first prodromal signs to prevent full episodes

Second-Line Alternatives:

1. Dopamine Antagonists:

   • Metoclopramide: Acts as both antiemetic and prokinetic
   • Haloperidol: Effective for breakthrough nausea/vomiting 1
   • Prochlorperazine: Phenothiazine that inhibits dopamine receptors

2. Benzodiazepines:

   • Lorazepam: 0.5-2 mg every 4-6 hours 1
   • Midazolam: Intravenous option for severe cases 3
   • Particularly helpful when anxiety is a component of episodes

3. Corticosteroids:

   • Dexamethasone: 8-12 mg daily 1
   • Particularly useful for breakthrough episodes

4. Cannabinoids (for refractory cases):

   • Nabilone: FDA-approved for nausea/vomiting that has not responded to conventional antiemetics 1
   • Note: Must distinguish from cannabinoid hyperemesis syndrome, which requires cannabis cessation 1

Treatment Algorithm

For Acute Episodes:

1. First attempt: Different 5-HT3 antagonist (if ondansetron failed, try granisetron - available as transdermal patch) 1
2. If still unresponsive: Add NK-1 receptor antagonist (aprepitant) 2
3. If still unresponsive: Add dopamine antagonist (metoclopramide, haloperidol) 1
4. For severe cases: Consider combination therapy with benzodiazepines (lorazepam) plus above medications 1, 3
5. For refractory cases: Consider cannabinoids (nabilone) or combination therapy with multiple agents using different mechanisms 1

For Prophylaxis Between Episodes:

1. Consider: Tricyclic antidepressants (amitriptyline) for prevention 1
2. Alternative: Anti-migraine medications (given CVS's relationship to migraine) 4, 5

Important Considerations

• Route of administration: During active vomiting, oral medications may not be feasible; consider IV, rectal, or transdermal routes 1
• Hydration: Ensure adequate fluid repletion and correct electrolyte abnormalities 1
• Scheduling: Use around-the-clock dosing rather than PRN during episodes 1
• Combination therapy: Multiple concurrent agents with different mechanisms of action may be necessary for refractory cases 1

Common Pitfalls to Avoid

1. Continuing failed therapy: If a medication class fails, switch to a different class rather than trying similar agents 1
2. Overlooking cannabinoid hyperemesis: In patients with chronic cannabis use, consider cannabinoid hyperemesis syndrome which requires cannabis cessation rather than additional antiemetics 1
3. Inadequate dosing: Ensure sufficient dosing and appropriate scheduling (around-the-clock rather than PRN) 1
4. Single-agent approach: Refractory CVS often requires combination therapy targeting multiple pathways 1
5. Ignoring triggers: Identify and address potential triggers (stress, certain foods, sleep deprivation) that may precipitate episodes 5

Remember that CVS management requires both abortive therapy for acute episodes and prophylactic therapy between episodes to reduce frequency and severity of attacks.