From the Guidelines
Lactulose is the recommended first-line alternative to rifaximin for preventing hepatic encephalopathy in patients with cirrhosis, typically dosed at 25-30 mL two to three times daily with the goal of achieving 2-3 soft bowel movements per day. This recommendation is based on the most recent and highest quality study available, which suggests that lactulose is effective in reducing the risk of recurrent hepatic encephalopathy and improving quality of life 1. For patients who cannot tolerate lactulose, other options include:
- Lactitol (20-30 g daily)
- Polyethylene glycol (PEG) laxatives
- Non-absorbable antibiotics like neomycin (1-2 g two to four times daily) or metronidazole (250 mg three times daily), though these antibiotics have more significant side effect profiles including ototoxicity and peripheral neuropathy with long-term use
- Probiotics may offer a supplementary approach, though evidence for their effectiveness is less robust
- Branched-chain amino acids can be considered in patients with protein intolerance
- Zinc supplementation (zinc acetate 220 mg twice daily) may benefit patients with zinc deficiency Management should also include addressing precipitating factors such as gastrointestinal bleeding, infection, electrolyte disturbances, and medication side effects. Dietary protein should generally not be restricted but distributed throughout the day in smaller meals. These alternatives can be used alone or in combination depending on patient response and tolerance. It is worth noting that rifaximin is often used in combination with lactulose, and the decision to use rifaximin alone or in combination with lactulose should be based on individual patient needs and response to treatment 1.
From the Research
Alternatives to Rifaximin for Preventing Hepatic Encephalopathy
- Lactulose: a non-absorbable disaccharide that is commonly used to treat hepatic encephalopathy 2, 3, 4, 5, 6
- Branched-chain amino acids: have been shown to have beneficial effects on the manifestations of hepatic encephalopathy in patients with cirrhosis 4
- L-ornithine L-aspartate: has been reported to have beneficial effects on the manifestations of hepatic encephalopathy in patients with cirrhosis 4
- Ornithine phenylacetate: a newer treatment that has been shown to have potentially beneficial effects on hepatic encephalopathy manifestations 4
- Spherical carbon: a newer treatment that has been shown to have potentially beneficial effects on hepatic encephalopathy manifestations 4
- Fecal microbiota transplant: a newer treatment that has been shown to have potentially beneficial effects on hepatic encephalopathy manifestations 4
- Metronidazole: an antibiotic that has been used to treat hepatic encephalopathy, but its use is limited due to the risk of serious adverse effects 3
- Neomycin: an antibiotic that has been used to treat hepatic encephalopathy, but its use is limited due to the risk of serious adverse effects 3
Comparison of Alternatives to Rifaximin
- Rifaximin has been shown to have a better efficacy and safety profile compared to lactulose and neomycin 3
- Rifaximin has been shown to be effective in the acute treatment of overt encephalopathy and in preventing recurrence 2
- The combination of rifaximin and lactulose has been shown to be superior to lactulose alone in the maintenance of hepatic encephalopathy remission 6