Can Rifaximin (Rifamycin derivative) be used as monotherapy in the treatment of Hepatic Encephalopathy?

From the Guidelines

Rifaximin should not be used as monotherapy for the treatment of Hepatic Encephalopathy, but rather as an add-on to lactulose for prevention of recurrent episodes, as recommended by the most recent guidelines 1. The use of rifaximin as monotherapy is not typically recommended due to limited data supporting its effectiveness in this context.

• The standard dosing for rifaximin is 550 mg twice daily.
• For acute hepatic encephalopathy, lactulose is the first-line treatment, with rifaximin usually added as an adjunctive therapy.
• Rifaximin works by reducing ammonia-producing gut bacteria with minimal systemic absorption, which makes it well-tolerated even in patients with advanced liver disease.
• It has fewer gastrointestinal side effects compared to lactulose, improving patient adherence.
• For patients experiencing their first episode of hepatic encephalopathy, starting with lactulose (typically 25-30 mL every 6-12 hours, titrated to produce 2-3 soft bowel movements daily) and adding rifaximin if response is inadequate provides the most evidence-based approach, as supported by recent guidelines 1. The most recent and highest quality study, a 2023 French recommendation, suggests that rifaximin can be used as an add-on to lactulose for prevention of recurrent episodes of HE, but it is difficult to recommend the use of rifaximin alone in the prevention 1.
• The study showed 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.
• However, the study also noted that approximately 90% of patients were also taking lactulose, highlighting the importance of combination therapy. Overall, while rifaximin can be effective in preventing recurrent episodes of hepatic encephalopathy, it should be used in conjunction with lactulose, rather than as monotherapy, to maximize its benefits and minimize its risks, as recommended by the most recent guidelines 1.

From the FDA Drug Label

XIFAXAN is a rifamycin antibacterial indicated for: • Reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults (1.2)

The FDA drug label indicates that Rifaximin can be used for the reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults.

• The recommended dosage regimen for HE is one 550 mg tablet 2 times a day.
• No direct information is provided in the label regarding the use of Rifaximin as monotherapy in the treatment of Hepatic Encephalopathy. However, based on the information provided, it can be inferred that Rifaximin is used to reduce the risk of overt HE recurrence, which implies its use as a treatment for HE.
• Caution should be exercised when XIFAXAN is administered to patients with severe hepatic impairment 2. It is essential to consult the full prescribing information and consider the patient's specific condition before making any clinical decisions.

From the Research

Rifaximin as Monotherapy in Hepatic Encephalopathy Treatment

• Rifaximin, a rifamycin derivative, has been studied for its efficacy in treating hepatic encephalopathy, with several studies indicating its potential as a monotherapy or add-on treatment 3, 4, 5.
• A study published in 2010 found that rifaximin was effective in improving behavioral, laboratory, mental, and intellectual abnormalities in patients with hepatic encephalopathy, and was generally found to be equal or superior to lactulose in clinical studies 3.
• Another study from 2010 demonstrated that rifaximin significantly reduced the risk of an episode of hepatic encephalopathy, as compared with placebo, over a 6-month period, with a hazard ratio of 0.42 4.
• However, most studies have investigated the use of rifaximin in combination with lactulose, rather than as a monotherapy, with one study finding that the combination of lactulose plus rifaximin was more effective than lactulose alone in the treatment of overt hepatic encephalopathy 6.
• There is limited direct evidence on the use of rifaximin as a monotherapy in the treatment of hepatic encephalopathy, with most studies focusing on its use in combination with other treatments or as an add-on therapy 7, 5.

Efficacy and Safety of Rifaximin

• Rifaximin has been shown to be well-tolerated and effective in reducing hospitalizations and improving outcomes in patients with hepatic encephalopathy 4, 5.
• The incidence of adverse events reported during studies was similar to that of placebo or lactulose, with rifaximin being considered a safe and effective treatment option for hepatic encephalopathy 3, 4.
• The dosage of rifaximin used in studies has varied, but most medical centers use a dosage of 400 mg three times a day or 550 mg twice a day for hepatic encephalopathy 3.