Why have providers avoided ordering VIBERZI (eluxadoline) for patients with irritable bowel syndrome with diarrhea (IBS-D)?

Why Providers Avoid Prescribing VIBERZI (Eluxadoline) for IBS-D

Providers avoid prescribing VIBERZI primarily due to its serious safety concerns, particularly the risk of pancreatitis and sphincter of Oddi spasm, especially in patients without a gallbladder, along with its limited efficacy for abdominal pain compared to other available treatments. 1

Safety Concerns

Serious Adverse Events

• Pancreatitis risk: 0.4% incidence reported in clinical trials 2
• Sphincter of Oddi Spasm (SOS): Particularly concerning in patients without a gallbladder 1
• In clinical trials, there were 5 cases of pancreatitis and 8 SOS events in patients treated with eluxadoline, with none in the placebo group 1

Contraindications

Eluxadoline is contraindicated in patients with:

• No gallbladder (post-cholecystectomy) 1
• History of sphincter of Oddi problems or dysfunction 1
• Alcohol dependence or consumption of more than 3 alcoholic beverages per day 1
• History of pancreatitis 3
• Biliary duct obstruction 2
• Severe liver impairment 1

Limited Efficacy

Modest Pain Relief

• Eluxadoline has less effect on abdominal pain compared to its effects on stool consistency and urgency 1
• In network meta-analyses comparing treatments for IBS-D, other medications ranked higher for pain relief:
  • Ramosetron 2.5 mcg daily ranked first
  • Ramosetron 5 mcg daily ranked second
  • Alosetron 1 mg twice daily ranked third 1

Overall Response Rates

• Only 22.7% of patients achieved composite response in the RELIEF study (vs. 10.3% with placebo) 4
• In phase III trials, approximately 25-30% of eluxadoline-treated patients achieved composite clinical response 3

Availability and Access Issues

Limited Availability

• "Although licensed for IBS-D, the drug is unavailable in many countries" 1
• This geographical limitation restricts prescribing options for many providers globally

Cost Considerations

• As a newer medication, cost and insurance coverage may be barriers to prescribing

Prescribing Algorithm for VIBERZI

1. First confirm IBS-D diagnosis using Rome criteria

2. Screen for absolute contraindications:

   • Absence of gallbladder
   • History of sphincter of Oddi dysfunction
   • Alcohol abuse/consumption >3 drinks daily
   • History of pancreatitis
   • Severe liver impairment

3. Consider alternative treatments first if:

   • Patient's primary complaint is abdominal pain (TCAs or 5-HT3 antagonists may be more effective) 1
   • Patient has mild symptoms (loperamide may be sufficient)

4. Consider VIBERZI when:

   • Patient has intact gallbladder
   • Patient has failed first-line therapies
   • Diarrhea and urgency are predominant symptoms rather than pain
   • No history of alcohol abuse

5. Dosing considerations:

   • Standard dose: 100 mg twice daily
   • Reduced dose (75 mg twice daily) for patients with:
     • Mild/moderate hepatic impairment
     • Inability to tolerate 100 mg dose
     • Concomitant OATP1B1 inhibitors 3

Monitoring Recommendations

• Educate patients about early signs of pancreatitis (severe abdominal pain, often radiating to back)
• Advise immediate discontinuation if severe abdominal pain occurs, especially after first few doses
• Monitor for constipation, which occurs in approximately 8% of patients 2

Despite these concerns, eluxadoline remains a conditional recommendation by the AGA for IBS-D treatment, particularly for patients with predominant diarrhea symptoms rather than pain, who have an intact gallbladder and no other contraindications 1.