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

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

For patients with cyclic vomiting syndrome (CVS) who do not respond to ondansetron, the next step should be combination therapy with sumatriptan and a different class of antiemetic, along with consideration of sedating agents such as benzodiazepines. 1

Alternative Antiemetic Options

When ondansetron fails to control symptoms in CVS, consider the following alternative antiemetics:

• Promethazine: 12.5-25 mg orally or per rectum every 4-6 hours during episodes 1

  • Advantages: Provides both antiemetic effect and sedation
  • Available as rectal suppository for patients actively vomiting
  • Side effects: CNS depression, anticholinergic effects, extrapyramidal symptoms

• Prochlorperazine: 5-10 mg orally every 6-8 hours or 25 mg suppository every 12 hours 1

  • Side effects: CNS depression, anticholinergic effects, extrapyramidal symptoms
  • Caution in patients with history of leukopenia, dementia, glaucoma, or seizure disorders

Add Sumatriptan as Combination Therapy

Most patients with CVS require combinations of at least 2 agents to reliably abort attacks 1. Sumatriptan should be added as it works through a different mechanism:

• Sumatriptan: 6 mg subcutaneous injection or 20 mg nasal spray at onset of episode 1
  • For nasal administration, use head-forward position to optimize medication contact with anterior nasal receptors
  • Limit to 2 doses in a 24-hour period
  • Contraindicated in patients with ischemic heart disease, stroke, peripheral vascular disease, or uncontrolled hypertension

Consider Sedating Agents

Inducing sedation is often an effective abortive strategy in CVS 1:

• Alprazolam: 0.5-2 mg every 4-6 hours 1

  • Available in sublingual and rectal forms
  • Caution in pregnancy and those with history of substance abuse

• Lorazepam: 0.5-2 mg every 4-6 hours 1

  • Can be administered orally, intravenously, or sublingually

• Diphenhydramine: 12.5-25 mg every 4-6 hours during episode 1

  • Provides antihistamine and anticholinergic effects
  • Caution in older adults, those with glaucoma, BPH, or cardiovascular disease

For Refractory Cases

If home management fails, consider:

1. Emergency department management with:

   • IV fluids with dextrose 1
   • IV benzodiazepines for sedation 1
   • IV ketorolac for pain (preferable to narcotics) 1
   • Sedating antipsychotics like droperidol or haloperidol 1

2. Novel agents for persistent cases:

   • Aprepitant: A neurokinin-1 receptor antagonist 1, 2
     • Has shown dramatic response in case reports of severe CVS
     • Dosing: 125 mg first day, 80 mg on days 2-3

3. Consider prophylactic therapy if episodes are frequent (>4 per year) and severe:

   • Tricyclic antidepressants as first-line prophylactic medications 1
   • Topiramate, aprepitant, zonisamide, or levetiracetam as second-line agents 1

Important Considerations

• Administer medications as early as possible in the prodromal phase for best results 1
• For patients actively vomiting, utilize non-oral routes (IV, rectal, sublingual, or nasal) 1
• Multiple concurrent agents in alternating schedules or routes may be necessary 1
• Ensure adequate hydration and correct any electrolyte abnormalities 1
• Identify and address triggers (stress, sleep disturbances, fasting) 1

Pitfalls to Avoid

• Relying on oral medications during active vomiting episodes
• Using single-agent therapy when most patients require combination approaches
• Delaying treatment until the emetic phase is fully established
• Overlooking the importance of sedation as a therapeutic goal
• Failing to consider non-narcotic approaches to pain management
• Repeated unnecessary diagnostic testing during episodes

By following this stepped approach with combination therapy targeting multiple pathways, most patients with CVS who fail ondansetron can achieve better symptom control and improved quality of life.