When to give Rifaximin in hepatic encephalopathy?

When to Give Rifaximin in Hepatic Encephalopathy

Rifaximin should be used as an add-on therapy to lactulose for prevention of recurrent episodes of hepatic encephalopathy after the second episode of overt hepatic encephalopathy. 1, 2

Primary Indications for Rifaximin

First-line approach:

• Lactulose is the first choice for treatment of episodic overt hepatic encephalopathy (OHE) 1
• Lactulose is recommended for prevention of recurrent episodes of HE after the initial episode 1

When to add rifaximin (550 mg twice daily):

1. After the second episode of OHE while on lactulose treatment 1, 2
2. When prevention with lactulose alone fails 2
3. As monotherapy when lactulose is poorly tolerated 2

Evidence Supporting Rifaximin Use

Rifaximin significantly reduces the risk of recurrent hepatic encephalopathy:

• 58% reduction in risk compared to placebo (hazard ratio 0.42; 95% CI 0.28-0.64; p<0.001) 3
• Breakthrough episodes occur in 22.1% of rifaximin-treated patients vs. 45.9% in placebo group 3
• Reduces hospitalization risk (13.6% vs. 22.6%; hazard ratio 0.50; 95% CI 0.29-0.87; p=0.01) 3

A recent meta-analysis confirmed these findings, showing lower recurrence rates with rifaximin (risk ratio = 0.61 [0.50,0.73], p = 0.001) without significant differences in adverse events or mortality 4.

Special Clinical Scenarios

TIPS (Transjugular Intrahepatic Portosystemic Shunt)

• Rifaximin can be considered for prophylaxis of HE prior to non-urgent TIPS placement 1
• Routine prophylactic therapy is not recommended for prevention of post-TIPS HE 1

Discontinuation of Therapy

• Consider discontinuation only when:
  • Precipitating factors have been well controlled (e.g., infections, variceal bleeding)
  • Liver function or nutritional status has significantly improved 1
  • The patient has recovered significant liver function and muscle mass 1

Dosing and Safety Considerations

• Standard dose: 550 mg twice daily 2, 5
• Use with caution in patients with severe hepatic impairment (Child-Pugh Class C) 2, 5
• Long-term use (>24 months) has shown continued effectiveness with a good safety profile 2
• No increased risk of bacterial resistance or C. difficile-associated colitis has been observed with long-term use 2

Common Pitfalls to Avoid

1. Not adding rifaximin after multiple episodes: Continuing lactulose alone despite recurrent episodes of HE
2. Inappropriate discontinuation: Stopping therapy prematurely when risk factors for recurrence persist
3. Inadequate dosing: Using once-daily dosing instead of the recommended twice-daily regimen (although some research suggests once-daily dosing may be effective in certain populations) 6
4. Failure to monitor for adverse effects: Not monitoring patients with severe hepatic impairment for potential complications
5. Using as primary monotherapy: Starting with rifaximin alone instead of lactulose as first-line therapy

Patient Education

Therapeutic education programs should be offered to patients and caregivers to:

• Improve medication adherence
• Help recognize early HE symptoms
• Limit hospitalizations 2

Remember that rifaximin is intended for long-term maintenance therapy to prevent recurrence of hepatic encephalopathy and should not be discontinued in patients with a history of recurrent episodes unless there is significant improvement in liver function or control of precipitating factors.