When is lactulose (lactulose) versus rifaximin (rifaximin) used in the treatment of hepatic encephalopathy?

From the Guidelines

Lactulose is the first-line treatment for hepatic encephalopathy, while rifaximin is typically used as an add-on therapy when lactulose alone is insufficient or as an alternative when lactulose is not tolerated. The most recent and highest quality study, published in 2023 1, supports the use of lactulose as the primary treatment, with rifaximin added on when necessary. Lactulose is initiated at 20-30 g orally 3-4 times per day, with the goal of achieving 2-3 bowel movements per day, as recommended by the 2020 guidelines 1. Rifaximin is prescribed at 550 mg twice daily, usually in combination with lactulose for prevention of recurrent episodes or for patients with persistent symptoms despite lactulose therapy.

Key Considerations

• Lactulose works by acidifying the colon, trapping ammonia and reducing its absorption, while rifaximin reduces ammonia-producing gut bacteria.
• Patients should be monitored for lactulose side effects including diarrhea, abdominal cramping, and electrolyte disturbances.
• Lactulose is less expensive than rifaximin, which is an important consideration for long-term therapy.
• For acute episodes, lactulose can also be administered as an enema (200 g lactulose in 700 mL water) when oral administration is not possible, as recommended by the 2020 guidelines 1.
• The 2022 guidelines 1 also support the use of lactulose as the primary treatment, with rifaximin added on when necessary, and highlight the importance of titrating lactulose to achieve 2-3 bowel movements per day.

Treatment Approach

• Lactulose is recommended as the first-line treatment for hepatic encephalopathy, with the goal of achieving 2-3 bowel movements per day.
• Rifaximin is recommended as an add-on therapy when lactulose alone is insufficient or as an alternative when lactulose is not tolerated.
• The treatment approach should be individualized based on the patient's response to therapy and the presence of any side effects.

From the FDA Drug Label

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. For the prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic pre-coma and coma.

The decision to use lactulose vs rifaximin in hepatic encephalopathy depends on the specific clinical scenario.

• Lactulose is used for the prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic pre-coma and coma.
• Rifaximin is used for the reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults, and is often used concomitantly with lactulose 2. It is essential to note that rifaximin has not been studied in patients with MELD scores >25, and its use in such patients is not recommended 2.

From the Research

Treatment Options for Hepatic Encephalopathy

The treatment of hepatic encephalopathy (HE) involves the use of nonabsorbable disaccharides, such as lactulose, and antibiotics, including rifaximin. The choice between lactulose and rifaximin depends on various factors, including the severity of the disease and the patient's response to treatment.

Lactulose vs Rifaximin

• Lactulose is considered the first-line therapeutic agent for treating HE, as it acidifies the gastrointestinal tract and inhibits the production of ammonia by coliform bacteria 3.
• Rifaximin, a semisynthetic, nonsystemic antibiotic, was approved in 2010 for the treatment of overt HE and has been shown to be effective in improving behavioral, laboratory, mental, and intellectual abnormalities in patients with HE 3.
• Studies have compared the efficacy of lactulose and rifaximin in the treatment of HE, with some showing that rifaximin is equal or superior to lactulose 3, 4, 5.
• However, other studies have found that the combination of rifaximin and lactulose is not superior to lactulose alone in the treatment of refractory HE 6, 7.

Combination Therapy

• The use of rifaximin in combination with lactulose has been shown to provide additional benefits in terms of increased effective rate and decreased mortality compared to lactulose alone 4, 5.
• However, the combination of rifaximin and lactulose may not be superior to lactulose alone in all cases, and the choice of treatment should be individualized based on the patient's specific needs and response to treatment 6, 7.

Clinical Considerations

• The dosage of rifaximin used in the treatment of HE has varied, but most medical centers use a dosage of 400 mg three times a day or 550 mg twice a day 3.
• The choice between lactulose and rifaximin should be based on the patient's clinical presentation, laboratory results, and response to treatment, as well as the presence of any contraindications or side effects 3, 6, 4, 5, 7.