What is the dosage of rifaximin (Xifaxan) in hepatic encephalopathy?

Rifaximin Dosage for Hepatic Encephalopathy

The recommended dosage of rifaximin for hepatic encephalopathy is 550 mg taken orally twice daily. 1

Evidence-Based Dosing Recommendations

The FDA-approved dosage of rifaximin (Xifaxan) for reducing the risk of overt hepatic encephalopathy (HE) recurrence in adults is clearly established:

• Dosage: 550 mg tablet taken orally twice daily 1
• Can be taken with or without food 1
• Approved for use in adults with liver disease to reduce recurrence of overt HE episodes 2

Clinical Evidence Supporting This Dosage

The recommended dosage is based on robust clinical evidence:

• A pivotal multinational, double-blind, placebo-controlled trial demonstrated that rifaximin 550 mg twice daily significantly reduced the risk of breakthrough HE episodes compared to placebo (hazard ratio 0.42; 95% CI, 0.28 to 0.64; p<0.001) 3
• This dosage significantly reduced HE-related hospitalizations (13.6% vs 22.6% in placebo group) 3
• Long-term studies have shown that efficacy is maintained with this dosage for up to 2.5 years of treatment 2

Combination Therapy Considerations

• In clinical trials, approximately 91% of patients were using lactulose concomitantly with rifaximin 1
• The French recommendations suggest rifaximin as an add-on therapy when lactulose alone fails in preventing recurrent overt HE 4
• Rifaximin can also be used alone when lactulose is poorly tolerated 4

Alternative Dosing Considerations

While some studies have investigated once-daily dosing (550 mg daily), the twice-daily regimen remains the standard of care:

• A comparative study found no significant difference between rifaximin 550 mg once daily versus twice daily in preventing HE recurrence (p=0.088) 5
• However, this single study has not changed the standard recommended dosage, and the FDA-approved regimen remains 550 mg twice daily 1

Important Clinical Caveats

• Rifaximin has not been extensively studied in patients with MELD scores >25, and only 8.6% of patients in controlled trials had MELD scores over 19 1
• There is increased systemic exposure in patients with severe hepatic impairment (Child-Pugh Class C), so caution should be exercised in these patients 1
• Rifaximin is not indicated for the treatment of acute episodes of HE but rather for reducing the risk of recurrence 1

Treatment Algorithm for HE Management

1. First-line therapy: Non-absorbable disaccharide (lactulose or lactitol) 4
2. Second-line/add-on therapy: Rifaximin 550 mg twice daily when lactulose alone fails to prevent recurrent HE 4
3. Alternative approach: Rifaximin 550 mg twice daily alone when lactulose is poorly tolerated 4

By following this evidence-based dosing regimen, clinicians can effectively reduce the recurrence of overt hepatic encephalopathy episodes, decrease HE-related hospitalizations, and improve quality of life in patients with liver disease.