From the Guidelines
Lactulose is recommended as the first-line treatment for hepatic encephalopathy, while rifaximin is recommended as an add-on therapy for patients who have recurrent episodes despite lactulose therapy. The typical dosage of lactulose is 25-30 mL orally every 1-2 hours until bowel movements occur, then adjusted to 15-45 mL 2-4 times daily to achieve 2-3 soft bowel movements per day 1. Rifaximin, a non-absorbable antibiotic, reduces ammonia-producing gut bacteria and is dosed at 550 mg twice daily 1.
Key Considerations
- Lactulose works by acidifying the colon, trapping ammonia as ammonium, and promoting its excretion 1.
- Rifaximin is particularly valuable for patients who have recurrent episodes despite lactulose therapy, cannot tolerate lactulose's side effects (bloating, diarrhea, abdominal discomfort), or have severe or refractory encephalopathy 1.
- The combination of both medications has shown superior outcomes in preventing recurrence compared to lactulose alone 1.
- Treatment should continue indefinitely in patients with recurrent hepatic encephalopathy unless they undergo liver transplantation, as discontinuation typically leads to recurrence 1.
Treatment Approach
- Identify and treat precipitating factors for HE 1.
- Use lactulose as the first choice for treatment of episodic OHE 1.
- Consider rifaximin as an effective add-on therapy to lactulose for prevention of OHE recurrence 1.
- Oral BCAAs can be used as an alternative or additional agent to treat patients nonresponsive to conventional therapy 1.
Evidence-Based Recommendations
- The 2022 EASL clinical practice guidelines recommend lactulose as secondary prophylaxis following a first episode of overt HE, and rifaximin as an adjunct to lactulose for secondary prophylaxis following >1 additional episodes of overt HE within 6 months of the first one 1.
- The 2023 French recommendations suggest rifaximin as an add-on to lactulose for prevention of recurrent overt HE 1.
From the FDA Drug Label
For the prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic pre-coma and coma. XIFAXAN is indicated for reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults. In the trials of XIFAXAN for HE, 91% of the patients were using lactulose concomitantly.
Lactulose is used for the prevention and treatment of hepatic encephalopathy, including the stages of hepatic pre-coma and coma 2. Rifaximin is used for the reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults, and is often used concomitantly with lactulose 3.
- Lactulose is typically used as a first-line treatment for hepatic encephalopathy.
- Rifaximin is used as an adjunctive therapy to reduce the risk of recurrence in patients with a history of hepatic encephalopathy.
From the Research
Treatment Options for Hepatic Encephalopathy
- Lactulose is considered the first-line therapeutic agent for treating hepatic encephalopathy, as it acidifies the gastrointestinal tract and inhibits the production of ammonia by coliform bacteria 4.
- Rifaximin, a semisynthetic, nonsystemic antibiotic, was approved for the treatment of overt hepatic encephalopathy and has been found to be equal or superior to lactulose in some studies 4.
Comparison of Lactulose and Rifaximin
- A study comparing rifaximin plus lactulose with lactulose alone found that the combination was effective in 96.87% of patients, while lactulose alone was effective in 85.71% of patients, although the difference was not statistically significant 5.
- Another study found that the use of rifaximin plus lactulose was associated with an increased incidence of effective rate and reduced risk of mortality compared to lactulose alone 6.
Add-on Therapy with Rifaximin
- Rifaximin add-on therapy has been found to reduce hospitalization rates and ammonia levels in patients with treatment-resistant hepatic encephalopathy 7.
- The combination of rifaximin and lactulose is recommended to prevent hepatic encephalopathy recurrence 8.