What are the equivalent medications to Viberzi (eluxadoline)?

Equivalent Medications for Viberzi (Eluxadoline)

For patients with diarrhea-predominant irritable bowel syndrome (IBS-D), 5-HT3 receptor antagonists (particularly ondansetron) are the most appropriate equivalent medication to Viberzi (eluxadoline) based on efficacy and safety profiles.

First-Line Alternatives to Viberzi

• Loperamide can be used as a first-line treatment for diarrhea in IBS-D, though it primarily addresses stool consistency rather than abdominal pain. Careful dose titration is recommended to avoid side effects such as constipation, bloating, and nausea 1
• Antispasmodics may help with global symptoms and abdominal pain in IBS-D, though they commonly cause dry mouth, visual disturbance, and dizziness 1

Second-Line Alternatives to Viberzi

• 5-HT3 receptor antagonists are considered the most efficacious drug class for IBS-D and serve as excellent alternatives to eluxadoline 1:

  • Ondansetron (titrated from 4 mg once daily to maximum 8 mg three times daily) is widely available and has a robust safety profile 1
  • Alosetron and ramosetron are highly effective but have limited availability in many countries 1

• Rifaximin, a non-absorbable antibiotic, is an efficacious second-line option for IBS-D, though its effect on abdominal pain is limited compared to eluxadoline 1, 2

Mechanism of Action Comparison

• Eluxadoline (Viberzi) is a mixed μ-opioid and κ-opioid receptor agonist and δ-opioid receptor antagonist that slows intestinal transit and reduces visceral hypersensitivity 1, 3
• 5-HT3 receptor antagonists (ondansetron, alosetron, ramosetron) slow gastrointestinal transit, reduce visceral hypersensitivity, and alter rectal compliance 1
• Rifaximin is a non-absorbable antibiotic with a different mechanism of action than eluxadoline 2

Efficacy Comparison

• 5-HT3 receptor antagonists are likely the most efficacious drug class for IBS-D 1, with clinical trials showing superior results compared to placebo for global symptoms, abdominal pain, and stool consistency 1
• Eluxadoline demonstrated efficacy in two large phase 3 trials with 27.2% of patients responding to the FDA composite endpoint versus 16.7% on placebo 1
• Rifaximin showed modest efficacy with approximately 9% more patients achieving adequate relief compared to placebo (40.7% vs 31.7%) 2

Safety Considerations

• Eluxadoline is contraindicated in patients without a gallbladder or those who drink more than 3 alcoholic beverages per day due to risk of pancreatitis and sphincter of Oddi spasm 1
• 5-HT3 receptor antagonists primarily cause constipation as a side effect 1
  • Alosetron has been associated with ischemic colitis, though rates since reintroduction are similar to background rates in female IBS patients 1
  • Ondansetron has a well-established safety profile with minimal serious adverse events 1
• Rifaximin has a favorable safety profile with minimal systemic absorption 2

Clinical Decision Algorithm

1. Assess patient characteristics:

   • If patient has no gallbladder or consumes >3 alcoholic drinks daily: Avoid eluxadoline, use ondansetron 1
   • If patient has severe IBS-D symptoms: Consider 5-HT3 antagonists as they are most efficacious 1

2. Treatment pathway:

   • Start with loperamide and/or antispasmodics as first-line therapy 1
   • If inadequate response, progress to second-line therapy:
     • Ondansetron: Start at 4 mg once daily, titrate to maximum 8 mg three times daily 1
     • Rifaximin: 550 mg three times daily for 14 days 2

3. Monitor for response and adverse effects:

   • Primary concern with 5-HT3 antagonists is constipation 1
   • Rifaximin may require repeated courses for sustained benefit 2

Special Considerations

• For patients with both IBS-D and psychological comorbidities, tricyclic antidepressants may be considered as they address both gut symptoms and psychological factors 1
• Eluxadoline produces analgesia centrally by modulating responses of spinal neurons, which may be important for patients with significant pain components 3