When is Rifaximin (Rifaximine) used vs Lactulose in the treatment of hepatic encephalopathy?

Lactulose vs. Rifaximin in Hepatic Encephalopathy Management

Lactulose is the first-line treatment for initial episodes of overt hepatic encephalopathy (OHE), while rifaximin should be added to lactulose after a second episode of OHE recurrence. 1

Initial Management of Hepatic Encephalopathy

• Lactulose is the first choice for treatment of episodic OHE with an initial dosing of 25 mL lactulose syrup every 1-2 hours until at least two soft bowel movements per day are produced 2, 1
• Maintenance dosing of lactulose should be titrated to maintain 2-3 bowel movements daily 1
• Lactulose works by acidifying the gastrointestinal tract, which inhibits ammonia production by coliform bacteria 3
• For severe HE (West-Haven criteria grade 3 or more) or patients unable to take medications orally, lactulose can be administered via nasogastric tube or as an enema (300 mL lactulose and 700 mL water) 3-4 times per day 2
• The FDA has approved lactulose for the prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic pre-coma and coma 4

Prevention of Recurrence

• Continue lactulose for prevention of recurrent episodes of HE after the initial episode 2, 1
• Add rifaximin to lactulose therapy after a second episode of OHE recurrence 2, 1
• Rifaximin is FDA-approved for reduction in risk of OHE recurrence in adults, with the recommended dose being one 550 mg tablet taken orally twice daily 5
• In clinical trials for rifaximin in HE, 91% of patients were using lactulose concomitantly 5
• The combination of rifaximin plus lactulose has shown better recovery from HE within 10 days (76% vs. 44%, P=0.004) and shorter hospital stays (5.8 vs. 8.2 days, P=0.001) than lactulose alone 2, 6

Special Considerations and Limitations

• Rifaximin should not be used alone without lactulose as there is no solid data supporting this approach 1
• Rifaximin has limited use in severe HE (West-Haven criteria grade 3 or more) due to the need for oral administration 2
• Rifaximin has not been studied in patients with MELD scores >25, and only 8.6% of patients in controlled trials had MELD scores over 19 5
• Avoid overuse of lactulose as it can lead to complications including aspiration, dehydration, hypernatremia, severe perianal skin irritation, and can even precipitate HE 1
• Routine prophylactic therapy (lactulose or rifaximin) is not recommended for prevention of post-TIPS HE 2, 1

Alternative Options for Non-responders

• For patients not responsive to conventional therapy, consider:
  • Oral branched-chain amino acids (BCAAs) 2, 1
  • IV L-ornithine L-aspartate (LOLA) 2, 1
  • Neomycin (alternative choice but limited by toxicity) 2, 7
  • Metronidazole (alternative choice but limited by toxicity) 2, 7

Algorithm for Management

1. First episode of OHE: Start lactulose 25 mL every 1-2 hours until 2 bowel movements per day, then titrate to maintain 2-3 soft stools daily 2, 1
2. After first episode: Continue lactulose for prevention of recurrence 2, 1
3. After second episode: Add rifaximin 550 mg twice daily to ongoing lactulose therapy 2, 1, 5
4. For non-responders: Consider adding LOLA, BCAAs, or (with caution) neomycin or metronidazole 2, 1

Common Pitfalls to Avoid

• Failing to identify and treat precipitating factors for HE 1
• Using rifaximin alone without lactulose 1
• Excessive lactulose dosing leading to complications 1
• Not considering rifaximin add-on therapy after multiple recurrences despite lactulose treatment 1
• Long-term use of neomycin or metronidazole leading to ototoxicity, nephrotoxicity, and neurotoxicity 1, 7