What is the recommended treatment for hepatic encephalopathy using Rifaximin (Rifaximin)?

Rifaximin for Hepatic Encephalopathy

Rifaximin 550 mg twice daily should be used as an add-on therapy to lactulose for secondary prophylaxis following recurrent episodes of overt hepatic encephalopathy, not as initial monotherapy or first-line treatment. 1, 2

Initial Treatment Approach

• Lactulose is the first-line treatment for overt hepatic encephalopathy, dosed at 20-30g (30-45 mL) orally 3-4 times daily, titrated to achieve 2-3 soft bowel movements per day. 1, 2, 3
• Approximately 90% of patients can be managed by identifying and correcting precipitating factors (gastrointestinal bleeding, infection, electrolyte disturbances, constipation, medications) combined with lactulose therapy. 4
• Lactulose significantly reduces recurrence risk (RR 0.44,95% CI: 0.31-0.64) and should never be bypassed in favor of rifaximin alone. 2, 5

When to Add Rifaximin

The European Association for the Study of the Liver recommends adding rifaximin 550 mg twice daily as secondary prophylaxis following more than one additional episode of overt hepatic encephalopathy within 6 months of the first episode. 1

• Rifaximin should be added when lactulose alone fails to prevent recurrence after a second breakthrough episode. 1, 2
• The combination of rifaximin plus lactulose reduces recurrence risk to 22.1% versus 45.9% with placebo plus lactulose (hazard ratio 0.42; 95% CI 0.28-0.64; p<0.001). 2, 6
• Combination therapy achieves better recovery rates within 10 days (76% vs 44%, p=0.004) and shorter hospital stays (5.8 vs 8.2 days, p=0.001) compared to lactulose alone. 2

FDA-Approved Dosing

• Rifaximin 550 mg tablet taken twice daily for reduction in risk of overt hepatic encephalopathy recurrence in adults. 3
• The medication can be taken with or without food. 3
• Long-term maintenance therapy with rifaximin for more than 24 months prevents recurrence with a good safety profile. 4, 7

Critical Limitations and Pitfalls

• Never use rifaximin as monotherapy for initial treatment of overt hepatic encephalopathy—it is not indicated and lacks evidence for this use. 4, 5
• Rifaximin has limited utility in severe hepatic encephalopathy (West-Haven grade 3 or higher) because it requires oral administration and patients may not be able to swallow safely. 5
• The high cost of rifaximin (approximately $1,500-2,000 per month) may be a significant barrier to routine use, though benefits in reducing hospitalizations may offset costs. 1, 5
• In critically ill patients with acute liver failure, there is insufficient evidence to recommend rifaximin. 1

Special Populations

• Use caution in patients with severe hepatic impairment (Child-Pugh Class C), though no specific dose adjustment is provided in the FDA label. 3
• Exercise caution when combining rifaximin with P-glycoprotein inhibitors (e.g., cyclosporine) as this may increase rifaximin absorption. 3
• Monitor INR and prothrombin time in patients taking warfarin, as dose adjustment may be needed. 3

Evidence for Mortality Benefit

• Meta-analysis of 19 RCTs (n=1,370) showed rifaximin reduced mortality (RR 0.50; 95% CI 0.31-0.82) and increased recovery from hepatic encephalopathy (RR 0.59; 95% CI 0.46-0.76). 1
• Rifaximin significantly reduced hepatic encephalopathy-related hospitalizations (13.6% vs 22.6%, hazard ratio 0.50; 95% CI 0.29-0.87; p=0.01). 6

Transplant Considerations

• Patients with recurrent or persistent hepatic encephalopathy despite adequate medical treatment should be evaluated for liver transplantation. 1, 4
• A first episode of overt hepatic encephalopathy should prompt referral to a transplant center for evaluation. 1