What are the next steps for treating cyclic vomiting disorder when patients are resistant to Zofran (ondansetron)?

Treatment Options for Cyclic Vomiting Syndrome Resistant to Ondansetron

For patients with cyclic vomiting syndrome who are resistant to ondansetron (Zofran), aprepitant should be considered as the next treatment option due to its demonstrated effectiveness in severe cases. 1

First-Line Alternative Treatments

When ondansetron fails to control cyclic vomiting syndrome (CVS), consider these next steps:

1. Aprepitant (NK-1 receptor antagonist):

   • Dosing: 125 mg on first day, followed by 80-85 mg on second and third days 1
   • Particularly effective when administered at the first prodromal signs
   • Has shown dramatic response in severe cases resistant to ondansetron

2. Tricyclic Antidepressants:

   • For prophylaxis in patients >5 years old 2
   • Amitriptyline is commonly used at doses around 85-90 mg/day 3
   • Note: Approximately 13% of patients may be non-responders to TCAs 3

3. Dexamethasone:

   • Dosage: 4-8 mg three to four times daily 4
   • Provides antiemetic effect
   • High strength of evidence for nausea management 4

Second-Line Options

If first-line alternatives fail, consider:

1. Metoclopramide:

   • Dosage: 10 mg IV/PO every 6 hours 4
   • Caution: Only use if no evidence of bowel obstruction
   • Monitor for extrapyramidal side effects and tardive dyskinesia 5

2. Olanzapine:

   • Dosage: 5-10 mg PO daily 4
   • Effective for breakthrough nausea and vomiting
   • Moderate strength of evidence

3. Phenothiazines:

   • Prochlorperazine: 5-10 mg every 6-8 hours 4
   • Promethazine: 12.5-25 mg PO/PR every 4-6 hours 4
   • Caution with history of leukopenia, dementia, or glaucoma

Management Principles for Breakthrough Emesis

1. Administration Strategy:

   • Use around-the-clock dosing rather than PRN 6
   • Consider IV or rectal routes when oral administration is not feasible due to vomiting 6

2. Combination Approach:

   • Use multiple agents with different mechanisms of action 6
   • Consider alternating schedules or routes of administration 6

3. Hydration and Electrolytes:

   • Ensure adequate hydration (≥1.5L/day) 4
   • Monitor and correct electrolyte abnormalities 6, 4

Risk Factors for Treatment Resistance

Be aware of factors that may predict poor response to standard therapy:

• History of migraine headaches 3
• Co-existing psychological disorders 3
• Chronic marijuana use 3
• Reliance on narcotics for pain control between episodes 3

Important Considerations

1. Rule out underlying causes:

   • Consider abdominal ultrasound to rule out urological causes like ureteropelvic junction obstruction 7
   • Evaluate for other potential triggers before labeling as idiopathic

2. Non-pharmacological interventions:

   • Dietary modifications: small, frequent meals; separating liquids from solids 4
   • Lifestyle changes: weight management, avoiding trigger foods, smoking cessation if applicable 4

3. For prolonged vomiting:

   • Consider thiamin supplementation if vomiting persists >2-3 weeks 4
   • Monitor for dehydration and electrolyte abnormalities 4

Remember that cyclic vomiting syndrome can be challenging to manage, and prevention is generally more effective than treating established episodes. A systematic approach using agents from different drug classes offers the best chance for symptom control in ondansetron-resistant cases.