Viberzi (Eluxadoline) Treatment Protocol for IBS-D
Dosing and Administration
Eluxadoline is FDA-approved at 100 mg twice daily with food for adults with IBS-D, with a lower 75 mg twice daily dose reserved for patients unable to tolerate the standard dose, those with mild-to-moderate hepatic impairment, or those receiving concomitant OATP1B1 inhibitors. 1, 2
- Take one tablet twice daily with food 2
- If a dose is missed, take the next dose at the regular time—never double up 2
- Treatment duration is continuous; efficacy is sustained over 26 weeks 1
Critical Absolute Contraindications
Eluxadoline is absolutely contraindicated in patients without a gallbladder due to severe risk of pancreatitis and sphincter of Oddi spasm, which can be fatal. 1, 2
Additional absolute contraindications include 2:
- Consumption of more than 3 alcoholic beverages per day
- History of pancreatitis or pancreatic duct obstruction
- History of sphincter of Oddi dysfunction or biliary duct obstruction
- Severe liver problems
- Chronic or severe constipation
- History of bowel obstruction
- Alcohol abuse or addiction
Clinical Positioning in Treatment Algorithm
The American Gastroenterological Association recommends eluxadoline as a second-line option when rifaximin is ineffective or when continuous daily therapy is preferred, particularly for patients with predominant diarrhea and urgency. 3
The treatment hierarchy for IBS-D is 3:
- First-line prescription: Rifaximin 550 mg three times daily for 14 days (best safety profile, retreatable)
- Second-line continuous therapy: Eluxadoline 100 mg twice daily with food OR ondansetron 4 mg daily
- For predominant abdominal pain: Consider amitriptyline 10-50 mg once daily
Expected Efficacy
Eluxadoline demonstrates moderate efficacy with 1:
- FDA endpoint responders: 27.2% vs 16.7% placebo (composite response of pain reduction and stool consistency improvement)
- Adequate relief: 38.4% vs 29.2% placebo for 6 of first 12 weeks
- Stool consistency improvement: Strong effect (RR 0.84; 95% CI 0.80-0.88)
- Urgency reduction: 50% urgency-free days achieved (RR 0.84; 95% CI 0.78-0.90)
- Quality of life: Clinically meaningful improvement (RR 0.84; 95% CI 0.74-0.95)
Common Adverse Events and Management
The most common adverse events are 1, 2:
- Constipation (8%): Stop eluxadoline immediately if severe constipation develops 2
- Nausea (7%)
- Abdominal pain (7%)
- Discontinuation rate due to adverse events: approximately 8% 1
Serious Adverse Events Requiring Immediate Action
Stop eluxadoline immediately and seek emergency care if the patient develops: 2
- New or worsening abdominal pain, especially in the upper right quadrant that may radiate to back or shoulder (pancreatitis or sphincter of Oddi spasm)
- Severe constipation
- Allergic reaction signs: facial/lip/tongue swelling, hives, rash, shortness of breath
Pancreatitis occurred in 0.3-0.4% of patients, typically within the first week but can occur after just 1-2 doses 1, 4, 5
Critical Drug Interactions
Do not combine eluxadoline with: 2
- Alosetron (increased constipation risk)
- Chronic loperamide use (increased constipation risk)
- Opioid pain medications (increased constipation risk)
- Anticholinergic medications (increased constipation risk)
Loperamide may be used occasionally for acute severe diarrhea but must be discontinued immediately if constipation develops 2
Special Populations
- Elderly patients (≥65 years): Have increased risk of serious adverse events and stomach problems compared to younger patients 2
- Hepatic impairment: Use 75 mg twice daily dose for mild-to-moderate impairment; contraindicated in severe impairment 1, 2
- Pregnancy/breastfeeding: Unknown safety profile 2
Common Pitfall to Avoid
The most critical error is prescribing eluxadoline to post-cholecystectomy patients—this population has the highest risk of severe pancreatitis and sphincter of Oddi spasm, which can be fatal. 1, 2, 4, 5 Always verify gallbladder status and alcohol consumption before prescribing.