What are the considerations for using Rifaximin in patients with liver disease?

From the Guidelines

Rifaximin can be safely used in patients with liver disease, including those with advanced cirrhosis, as it has minimal systemic absorption and is primarily eliminated unchanged in the feces. The standard dosage for hepatic encephalopathy is 550 mg twice daily, with no dose adjustment required for hepatic impairment 1. Rifaximin is particularly valuable in liver disease patients as it's FDA-approved for reducing the risk of recurrent hepatic encephalopathy episodes by decreasing ammonia-producing gut bacteria. It's also used off-label for spontaneous bacterial peritonitis prophylaxis and management of small intestinal bacterial overgrowth in cirrhotic patients.

Some key considerations for using Rifaximin in patients with liver disease include:

• The medication has a favorable safety profile with minimal drug interactions due to its limited systemic absorption, making it suitable for patients on multiple medications 1.
• Clinicians should monitor for potential side effects including nausea, bloating, and abdominal discomfort.
• Rifaximin works by inhibiting bacterial RNA synthesis, reducing intestinal bacterial load without promoting significant bacterial resistance, which is particularly important in the chronic or recurrent treatment often needed in liver disease patients.
• The use of rifaximin as an add-on to lactulose is recommended for prevention of recurrent episodes of hepatic encephalopathy after the second episode 1.
• Rifaximin alone can be used to prevent recurrence of hepatic encephalopathy when lactulose is poorly tolerated in patients with cirrhosis 1.

Overall, the current evidence supports the use of Rifaximin in patients with liver disease, including those with advanced cirrhosis, due to its efficacy in reducing the risk of recurrent hepatic encephalopathy episodes and its favorable safety profile 1.

From the FDA Drug Label

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 systemic exposure of rifaximin was markedly elevated in patients with hepatic impairment compared to healthy subjects The mean AUCτ in patients with hepatic impairment of Child-Pugh Class A, B, and C was 10-, 14-, and 21-fold higher, respectively, compared to that in healthy subjects

Considerations for using Rifaximin in patients with liver disease:

• Caution should be exercised when administering rifaximin to patients with severe hepatic impairment.
• Systemic exposure of rifaximin is markedly elevated in patients with hepatic impairment.
• Patients with Child-Pugh Class C hepatic impairment have a 2-fold higher mean AUC compared to those with Child-Pugh Class A hepatic impairment.
• Concomitant use of P-gp inhibitors, such as cyclosporine, may further increase systemic exposure to rifaximin in patients with hepatic impairment 2.

From the Research

Considerations for Using Rifaximin in Patients with Liver Disease

• Rifaximin is a minimally absorbed antibiotic that has been shown to be effective in the treatment of hepatic encephalopathy, a complication of liver disease 3, 4, 5, 6, 7.
• The efficacy of rifaximin in preventing episodes of hepatic encephalopathy has been established in several studies, including a randomized, double-blind, placebo-controlled trial that found rifaximin to be superior to placebo in reducing the risk of an episode of hepatic encephalopathy 3.
• Rifaximin has also been shown to be effective in reducing the risk of hospitalization involving hepatic encephalopathy, with one study finding that rifaximin reduced the risk of hospitalization by 50% compared to placebo 3.
• The safety and tolerability of rifaximin have been evaluated in several studies, with most finding that rifaximin is well-tolerated and associated with fewer adverse events than other treatments for hepatic encephalopathy, such as lactulose 4, 5, 7.
• Rifaximin has been compared to other treatments for hepatic encephalopathy, including lactulose and neomycin, and has been found to have a similar or superior efficacy and safety profile 4, 5, 7.

Key Findings

• Rifaximin significantly reduced the risk of an episode of hepatic encephalopathy compared to placebo (hazard ratio 0.42,95% CI 0.28-0.64, p<0.001) 3.
• Rifaximin reduced the risk of hospitalization involving hepatic encephalopathy by 50% compared to placebo (hazard ratio 0.50,95% CI 0.29-0.87, p=0.01) 3.
• Rifaximin was found to be as safe and effective as lactulose for the treatment of hepatic encephalopathy in a prospective randomized study 7.
• Rifaximin has been shown to be effective in reducing blood ammonia levels, improving mental status, and reducing the number of hospitalizations in patients with hepatic encephalopathy 4, 5, 6, 7.