Rifaximin in Hepatic Encephalopathy
Rifaximin is recommended as an add-on therapy to lactulose for long-term prevention of recurrent hepatic encephalopathy after a second episode or when lactulose alone fails, at a dosage of 550 mg twice daily. 1
Role in Treatment Algorithm
First-Line Treatment
- Lactulose remains the established first-line treatment for initial episodes of overt hepatic encephalopathy
- Dosage should be titrated to achieve 2-3 bowel movements per day 1
Prevention of Recurrence
- Combination therapy with rifaximin and lactulose is superior to lactulose alone:
- Reduces risk of HE recurrence with hazard ratio of 0.42 (95% CI: 0.28-0.64) 1, 2
- Decreases HE recurrence rate from 45.9% to 22.1% compared to placebo 2
- Reduces HE-related hospitalizations by 58% compared to placebo 1
- Improves treatment effectiveness (RR, 1.30; 95% CI, 1.10-1.53) 1
- Reduces mortality (RR, 0.57; 95% CI, 0.41-0.80) compared to lactulose alone 1
Alternative Therapy
- Rifaximin may be considered as monotherapy in patients who cannot tolerate lactulose due to side effects 1
- Generally better tolerated than lactulose 1
Dosing Considerations
- Standard dosage: 550 mg twice daily for hepatic encephalopathy 1, 3
- Once-daily dosing (550 mg daily) has been studied but is not FDA-approved and evidence is limited 4
- Can be taken with or without food, though high-fat meals may increase systemic exposure 3
Special Populations and Precautions
Hepatic Impairment
- Use with caution in patients with severe hepatic impairment (Child-Pugh Class C) 1, 3
- Systemic exposure increases with worsening hepatic function:
- 10-fold higher in Child-Pugh Class A
- 14-fold higher in Child-Pugh Class B
- 21-fold higher in Child-Pugh Class C 3
- Limited data in patients with MELD scores >25 1
Safety Considerations
- Monitor for Clostridium difficile-associated diarrhea 1, 3
- Long-term use has not shown increased risk of bacterial resistance 1
- Most common adverse reactions in HE patients (≥10%): peripheral edema, nausea, dizziness, fatigue, and ascites 3
- Monitor for drug interactions, particularly with warfarin 3
- Cost implications should be considered as rifaximin is significantly more expensive than lactulose 1
Patient Education and Monitoring
- Therapeutic education programs should be offered to patients and caregivers to:
- Improve medication adherence
- Help recognize early symptoms of hepatic encephalopathy
- Limit hospitalizations 1
- Monitor for improvement in symptoms 1
Evidence Quality and Limitations
- The recommendation for combination therapy is based on high-quality evidence from randomized controlled trials 2
- Meta-analyses confirm rifaximin's beneficial effect on HE recovery and potential mortality reduction 5, 6
- More than 90% of patients in pivotal trials received concomitant lactulose therapy, supporting the combination approach 2