When is rifaximin (Xifaxan) preferred over lactulose in treating hepatic encephalopathy?

When to Use Rifaximin Over Lactulose in Hepatic Encephalopathy

Lactulose should be used as first-line therapy for hepatic encephalopathy, with rifaximin recommended as an add-on therapy when lactulose alone fails to prevent recurrence, or as monotherapy when lactulose is poorly tolerated. 1

First-Line Treatment: Lactulose

• Lactulose is the first-choice treatment for both acute episodes and prevention of recurrent hepatic encephalopathy 1, 2
• Non-absorbable disaccharides (lactulose or lactitol) significantly reduce the risk of recurrent hepatic encephalopathy (RR = 0.44,95% CI: 0.31–0.64) 1
• Lactulose should be titrated to achieve 2-3 soft bowel movements per day 1, 2
• Proper dosing of lactulose is crucial - overuse can lead to complications such as aspiration, dehydration, hypernatremia, and severe perianal skin irritation 1

When to Use Rifaximin

1. As Add-On Therapy When Lactulose Fails

• Rifaximin should be added when lactulose alone fails to prevent recurrence of hepatic encephalopathy 1
• A landmark RCT showed that rifaximin (550 mg twice daily) added to lactulose reduced the risk of hepatic encephalopathy recurrence to 22.1% versus 45.9% with placebo plus lactulose (hazard ratio 0.42) 3
• Addition of rifaximin to lactulose in treatment-resistant patients significantly reduces hospitalization rates (from 41.6% to 22.2%, p=0.02) 4

2. When Lactulose is Poorly Tolerated

• Rifaximin monotherapy can be used when lactulose is poorly tolerated, though this is based on expert opinion rather than high-grade evidence 1, 5
• Rifaximin has better tolerability than lactulose with fewer gastrointestinal side effects 6
• The recommended dose is 550 mg twice daily or 400 mg three times daily when used as monotherapy 5

3. During Temporary Discontinuation of Lactulose

• When lactulose must be temporarily discontinued due to severe diarrhea, rifaximin can be used as the primary treatment until lactulose can be reintroduced 5
• Rifaximin remains in the intestine without being absorbed, so it doesn't cause additional diarrhea 5

Efficacy and Safety Considerations

• Rifaximin has shown beneficial effects on complete resolution of hepatic encephalopathy and mortality in multiple studies 1
• Long-term treatment with rifaximin (>24 months) has demonstrated a good safety profile with no increased risk of bacterial resistance or Clostridium difficile-associated colitis 1
• Combination therapy with rifaximin and lactulose shows better recovery from hepatic encephalopathy (76% vs. 44%, p=0.004) and shorter hospital stays (5.8 vs. 8.2 days, p=0.001) compared to lactulose alone 2

Common Pitfalls to Avoid

• Not recognizing and treating precipitating factors for hepatic encephalopathy, regardless of medication choice 2
• Discontinuing therapy after initial improvement - maintenance therapy is needed to prevent recurrence 2
• Using rifaximin alone as first-line therapy without sufficient evidence - current guidelines recommend it primarily as an add-on to lactulose 1
• Failing to properly titrate lactulose to achieve 2-3 bowel movements daily, which can lead to treatment failure 2

Treatment Algorithm

1. Start with lactulose as first-line therapy, titrated to achieve 2-3 soft bowel movements daily 1, 2
2. If recurrent episodes of hepatic encephalopathy occur despite optimal lactulose therapy, add rifaximin 550 mg twice daily 1, 3
3. If lactulose is poorly tolerated (severe diarrhea, abdominal pain), consider rifaximin monotherapy 1, 5
4. For all patients, identify and treat precipitating factors for hepatic encephalopathy 1, 2