What is the role of Rifaximin (Rifaximina) in the treatment of hepatic encephalopathy?

From the Guidelines

Rifaximin is recommended as an add-on to lactulose for the prevention of recurrent episodes of hepatic encephalopathy, particularly in patients who have experienced at least two episodes of overt HE within the previous 6 months, at a dose of 550 mg taken orally twice daily. This recommendation is based on the most recent and highest quality study available, which demonstrated that rifaximin reduced the risk of recurrent HE by 58% compared to placebo, and also reduced the risk of readmissions and improved quality of life 1.

Key Points

• Rifaximin works by reducing ammonia-producing bacteria in the gut without being significantly absorbed into the bloodstream, making it well-tolerated with minimal side effects.
• It is typically used alongside lactulose (usual dose 25-30 mL two to three times daily, titrated to produce 2-3 soft bowel movements daily) for optimal management.
• Patients should continue rifaximin indefinitely as long as they have cirrhosis and a history of hepatic encephalopathy, as stopping treatment often leads to recurrence.
• Common side effects include nausea, bloating, and diarrhea, but these are generally mild.
• Rifaximin is contraindicated in patients with intestinal obstruction.
• For acute episodes of hepatic encephalopathy, lactulose is typically the first-line treatment, with rifaximin added for those who don't respond adequately or for prevention of future episodes.

Management Considerations

• The use of rifaximin alone may be considered for patients who are intolerant to lactulose, as suggested by expert opinion 1.
• A therapeutic education program should be offered to the patient and caregiver to improve quality of life and limit hospitalizations 1.
• The French recommendations suggest the use of a non-absorbable disaccharide (lactulose or lactitol) as first-line treatment for preventing the recurrence of hepatic encephalopathy, with rifaximin added in cases of failed prevention 1.

Clinical Guidelines

• The European Association for the Study of the Liver and the American Association for the Study of Liver Diseases recommend lactulose as first-line treatment for prevention of recurrent episodes of HE, with rifaximin as an add-on for patients who experience recurrent episodes despite lactulose therapy 1.
• The EASL clinical practice guidelines recommend rifaximin as an adjunct to lactulose for secondary prophylaxis following more than one additional episode of overt HE within 6 months of the first one 1.

From the FDA Drug Label

Hepatic Encephalopathy Mean rifaximin exposure (AUCτ) in patients with a history of HE was approximately 12-fold higher than that observed in healthy subjects. Among patients with a history of HE, the mean AUC in patients with Child-Pugh Class C hepatic impairment was 2-fold higher than in patients with Child-Pugh Class A hepatic impairment [see Warnings and Precautions ( 5. 4), Use in Specific Populations (8.7)].

Rifaximina is used for the treatment of Hepatic Encephalopathy (HE). The mean rifaximin exposure in patients with a history of HE is approximately 12-fold higher than that observed in healthy subjects. Additionally, in patients with HE, the mean AUC in patients with Child-Pugh Class C hepatic impairment is 2-fold higher than in patients with Child-Pugh Class A hepatic impairment 2.

From the Research

Efficacy of Rifaximina for Hepatic Encephalopathy

• Rifaximina has shown a general trend toward better efficacy versus lactulose or neomycin in the treatment of hepatic encephalopathy (HE) 3.
• The combination of rifaximin and lactulose may be considered in the treatment of HE and in patients refractory to monotherapy 4.
• A systematic review and meta-analysis 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 in patients with HE 5.
• Rifaximin is effective in the acute treatment of overt encephalopathy and in preventing recurrence 6.

Safety and Tolerability of Rifaximina

• Rifaximin seems to offer a better safety and tolerability profile than that of lactulose and possibly neomycin 3.
• Rifaximin was found to be associated with fewer hospitalizations, fewer days of hospitalization, and lower hospitalization charges than were seen with lactulose 7.
• Rifaximin also had a better tolerance profile than the comparative agents 7.

Clinical Use of Rifaximina

• Rifaximin should be initiated during an episode of HE if, after 24-48 hours of non-absorbable disaccharide therapy, there is no clinical improvement 6.
• In recurrent HE, it is advisable to add rifaximin in patients under non-absorbable disaccharide therapy who develop a new episode 6.
• Standard treatment with rifaximin for minimal HE is not recommended 6.