When to wean off Xifaxan (rifaximin) for hepatic encephalopathy?

Rifaximin for Hepatic Encephalopathy: When to Wean Off

Rifaximin should not be discontinued in patients with a history of recurrent hepatic encephalopathy, as it is intended for long-term maintenance therapy to prevent recurrence. 1, 2

Rifaximin Treatment Approach

Rifaximin is a key medication for preventing recurrence of hepatic encephalopathy (HE) in patients with liver cirrhosis. The standard approach includes:

• Standard dosing: 550 mg twice daily for prevention of HE recurrence 2
• Primary use: As add-on therapy to lactulose or as monotherapy when lactulose is not tolerated 1, 2
• Duration: Long-term maintenance therapy (>24 months has shown continued effectiveness with good safety profile) 1, 2

Evidence Supporting Long-term Use

The 2023 French recommendations strongly support continued use of rifaximin for prevention of HE recurrence 1:

• A landmark double-blind, placebo-controlled trial demonstrated that rifaximin reduced the risk of recurrent HE by 58% compared to placebo (hazard ratio 0.42) 3
• Long-term open-label treatment with rifaximin for more than 24 months has shown continued prevention of HE recurrence with a good safety profile 1
• Rifaximin significantly reduces hospitalizations involving HE (13.6% vs 22.6% with placebo) 3
• Quality of life is significantly improved with continued rifaximin therapy 4

Treatment Algorithm for HE Management

1. First-line prevention: Non-absorbable disaccharides (lactulose or lactitol) 1
2. Second-line/add-on therapy: Add rifaximin 550 mg twice daily when:
   • Prevention with lactulose alone fails 1
   • Patient experiences recurrent episodes despite lactulose therapy 2
3. Alternative approach: Consider rifaximin monotherapy when lactulose is poorly tolerated 1, 2

Important Considerations

• No weaning protocol exists: Unlike lactulose, which is dose-titrated based on bowel movements, rifaximin is maintained at a fixed dose 1
• Safety profile: Long-term rifaximin use has not shown increased risk of bacterial resistance or Clostridium difficile-associated colitis 1
• Cost considerations: The high cost of rifaximin may impact long-term adherence, which should be discussed with patients 2
• Dosing optimization: While standard dosing is 550 mg twice daily, some research suggests once-daily dosing (550 mg) may be equally effective in preventing HE recurrence, potentially reducing cost 5

Common Pitfalls to Avoid

• Premature discontinuation: Stopping rifaximin can lead to recurrence of HE episodes, increased hospitalizations, and decreased quality of life 3, 4
• Inadequate patient education: Therapeutic education programs should be offered to patients and caregivers to improve medication adherence and recognition of early HE symptoms 1
• Failure to monitor concomitant therapy: Over 90% of patients in clinical trials received concomitant lactulose therapy with rifaximin 3, so maintaining appropriate lactulose dosing remains important

In summary, rifaximin is intended as a long-term maintenance therapy for preventing recurrence of hepatic encephalopathy, and current guidelines do not recommend weaning patients off this medication if they have a history of recurrent HE.