Does adding rifaximin (Rifaximin) to lactulose therapy benefit patients with refractory hepatic encephalopathy?

From the Guidelines

Adding rifaximin to lactulose therapy is a highly recommended approach for patients with refractory hepatic encephalopathy, as it significantly reduces the risk of breakthrough episodes and improves quality of life. The standard dosing for rifaximin is 550 mg twice daily, which can be added to ongoing lactulose therapy, typically dosed at 25-30 mL every 6-12 hours, titrated to 2-3 soft bowel movements daily 1. This combination therapy has been shown to reduce the risk of recurrent hepatic encephalopathy by about 58% compared to lactulose alone, and decreases hospitalization rates, as demonstrated in a recent international, double-blind, placebo-controlled RCT including 299 cirrhotic patients 1.

Some key points to consider when using rifaximin in combination with lactulose include:

• Rifaximin works by reducing ammonia-producing gut bacteria while having minimal systemic absorption, complementing lactulose's mechanism of decreasing ammonia production and absorption in the colon 1.
• The combination addresses the condition through different but complementary pathways, making it more effective than either agent alone.
• Patients generally tolerate rifaximin well with minimal side effects, which is particularly important in this vulnerable population 1.
• For patients with refractory hepatic encephalopathy who continue to have symptoms despite optimal lactulose therapy, adding rifaximin should be considered a standard approach to management, as recommended by recent guidelines 1.

Overall, the addition of rifaximin to lactulose therapy is a well-supported and effective strategy for managing refractory hepatic encephalopathy, with a strong evidence base and minimal risks of adverse effects 1.

From the Research

Benefits of Adding Rifaximin to Lactulose Therapy

• The addition of rifaximin to lactulose therapy has been shown to be effective in reducing the recurrence of overt hepatic encephalopathy and hospitalizations in patients with cirrhosis 2, 3, 4.
• Rifaximin has been found to be equal or superior to lactulose in improving behavioral, laboratory, mental, and intellectual abnormalities in patients with hepatic encephalopathy 5.
• The combination of lactulose and rifaximin has been shown to be more effective than lactulose alone in the treatment of overt hepatic encephalopathy, with a significant decrease in mortality and hospital stay 2.
• Long-term studies have demonstrated that the addition of rifaximin to lactulose therapy significantly reduces the risk of overt hepatic encephalopathy recurrence and HE-related hospitalization, without compromising tolerability 3.

Comparison of Rifaximin and Lactulose

• Rifaximin and lactulose have been compared in several studies, with rifaximin being found to be equally effective or superior to lactulose in maintaining remission from overt hepatic encephalopathy 5, 2, 4.
• Rifaximin has been shown to be safe and well-tolerated in long-term maintenance of remission from overt hepatic encephalopathy, although it may not be cost-effective compared to lactulose therapy in covert hepatic encephalopathy 6.

Clinical Implications

• The evidence suggests that adding rifaximin to lactulose therapy may be beneficial in patients with refractory hepatic encephalopathy, particularly in reducing the risk of recurrence and hospitalization 2, 3, 4.
• Clinicians should consider the use of rifaximin in combination with lactulose as a treatment option for patients with overt hepatic encephalopathy, taking into account the individual patient's needs and medical history 5, 2, 3.