What is a suitable permanent substitution for Xifaxan (rifaximin) in a patient with hepatic encephalopathy who is also on lactulose?

Permanent Substitution for Rifaximin in Hepatic Encephalopathy Management

When rifaximin is unavailable for a patient on combination therapy with lactulose for hepatic encephalopathy prevention, neomycin is the most appropriate permanent substitution. 1

Alternative Medication Options

• Neomycin is recommended as an alternative choice for treatment of overt hepatic encephalopathy with a Grade II-1, B, 2 recommendation by the American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL) 1
• Metronidazole is another alternative choice for treatment of overt hepatic encephalopathy (Grade II-3, B, 2), but has significant limitations for long-term use 1
• L-Ornithine-L-Aspartate (LOLA) can be used as an alternative agent for patients nonresponsive to conventional therapy (Grade I, B, 2) 1, 2

Advantages and Limitations of Each Option

Neomycin

• Has been widely used in the past for HE treatment and is a known glutaminase inhibitor 1
• Effective in reducing ammonia levels and improving encephalopathy symptoms 3
• Important limitation: Long-term use carries risks of ototoxicity, nephrotoxicity, and neurotoxicity 1
• Recommended dosing: 1-2 g orally 2-4 times daily 3

Metronidazole

• Effective for short-term therapy of hepatic encephalopathy 1
• Significant limitation: Long-term ototoxicity, nephrotoxicity, and neurotoxicity make it unattractive for continuous long-term use 1
• Should be considered only if other options are unavailable or contraindicated 3

L-Ornithine-L-Aspartate (LOLA)

• Works by helping metabolize ammonia to urea and glutamine 2
• Clinical benefit includes lowering plasma ammonia concentrations and improving hepatic encephalopathy symptoms 2
• Can be administered intravenously at 30g/day for severe cases 2
• May be particularly useful when other options are not tolerated 2

Management Algorithm for Rifaximin Substitution

1. First-line substitution: Continue lactulose at current dose and add neomycin 1-2g orally 2-4 times daily 1, 3
2. Monitor for side effects: Regularly assess renal function, hearing, and neurological status while on neomycin 1, 3
3. If neomycin is not tolerated: Consider metronidazole for short-term use only, or LOLA as an alternative 1, 2
4. Maintain lactulose therapy: Continue lactulose with goal of 2-3 soft bowel movements per day 4, 3

Important Clinical Considerations

• Lactulose remains the cornerstone of therapy and should be continued even when adding an alternative to rifaximin 4
• Regular monitoring of renal function is essential when using neomycin due to nephrotoxicity risk 1, 3
• Avoid simple laxatives as they lack the prebiotic properties of disaccharides like lactulose 4
• Continue to identify and treat any precipitating factors for hepatic encephalopathy (infections, GI bleeding, electrolyte disturbances, etc.) 4, 3
• Consider probiotics as a potential adjunctive therapy, as some studies show they may have similar efficacy to lactulose in preventing HE recurrence 1

Comparative Efficacy

• While rifaximin added to lactulose is the best-documented agent to maintain remission in patients with recurrent HE 1, 5, studies show neomycin can be similarly effective in improving neurologic signs and symptoms and reducing blood ammonia levels 6
• In comparative studies, rifaximin has shown similar efficacy to lactulose with better tolerability 7, but when rifaximin is unavailable, neomycin remains a viable alternative 1, 3