Can you titrate rifaximin (Rifaximin) dose in hepatic encephalopathy?

From the Guidelines

Rifaximin dosing can be titrated in hepatic encephalopathy, with the standard dose of 550 mg twice daily typically maintained without adjustment for most patients, as supported by the most recent guidelines 1. In cases of severe hepatic impairment or poor tolerance, physicians may consider reducing to 550 mg once daily initially, with gradual titration back to the standard dose as tolerated. For patients experiencing breakthrough episodes despite standard dosing, temporary increases to 550 mg three times daily have been used in clinical practice, though this is off-label. Rifaximin works by reducing ammonia-producing gut bacteria without significant systemic absorption, making it generally well-tolerated even in advanced liver disease. Some key points to consider when using rifaximin for hepatic encephalopathy include:

• The maximum dose is 1,200 mg/day, which might limit its use in cases of severe HE 1.
• Rifaximin has been shown to reduce the risk of recurrent HE by 58% compared to placebo, and also reduced the risk of readmissions and improved quality of life 1.
• The use of rifaximin in combination with lactulose is recommended for the prevention of recurrent episodes of HE after the second episode 1.
• Dose adjustments should be made under medical supervision with monitoring for clinical response and side effects such as nausea, bloating, or diarrhea. Rifaximin is typically used as a long-term maintenance therapy to prevent recurrent episodes of hepatic encephalopathy, often in combination with lactulose for optimal management.

From the FDA Drug Label

No dosage adjustment is recommended because rifaximin is presumably acting locally Nonetheless, caution should be exercised when XIFAXAN is administered to patients with severe hepatic impairment [see Warnings and Precautions (5.4), Clinical Pharmacology (12.3), Clinical Studies (14. 2)].

The FDA drug label does not provide guidance on titrating the rifaximin dose in hepatic encephalopathy. Caution is advised when administering XIFAXAN to patients with severe hepatic impairment, but no specific dosage adjustment recommendations are made. 2

From the Research

Rifaximin Dose Titration in Hepatic Encephalopathy

• The efficacy of rifaximin in treating hepatic encephalopathy is well-documented, but the optimal dosing strategy is still being studied 3, 4, 5, 6.
• A study published in 2010 found that rifaximin significantly reduced the risk of an episode of hepatic encephalopathy, as compared with placebo, over a 6-month period 3.
• Another study published in 2015 compared once a day rifaximin to twice a day dosage in the prevention of recurrence of hepatic encephalopathy in patients with chronic liver disease, and found no significant difference between the two dosing regimens 4.
• However, a study published in 2014 found that treatment with rifaximin failed to maintain remission from hepatic encephalopathy more effectively than placebo in the studied group 7.
• The typical dosage of rifaximin used in clinical trials is 550 mg twice daily, but some studies have used 400 mg three times a day 5.
• Rifaximin has been shown to be effective in improving behavioral, laboratory, mental, and intellectual abnormalities in patients with hepatic encephalopathy, and is generally well-tolerated 5, 6.

Dosing Considerations

• The dosage of rifaximin may need to be adjusted based on the individual patient's response to treatment and the presence of any adverse events 5, 6.
• Patients with hepatic encephalopathy may require ongoing treatment with rifaximin to prevent recurrence of the condition 3, 4, 6.
• The use of rifaximin in combination with lactulose may be beneficial in reducing the risk and duration of hospitalizations for hepatic encephalopathy 6.