From the Guidelines
Rifaximin is an effective treatment for hepatic encephalopathy, working primarily by reducing ammonia-producing bacteria in the gut through its mechanism of inhibiting bacterial RNA synthesis by binding to bacterial DNA-dependent RNA polymerase, as supported by the most recent evidence from 2023 1.
Mechanism of Action
Rifaximin is a non-absorbable antibiotic that remains in the gastrointestinal tract, where it exerts its effect. This action reduces the number of ammonia-producing bacteria in the intestines, thereby decreasing ammonia production and absorption into the bloodstream.
Key Points
- Ammonia is a key neurotoxin in hepatic encephalopathy that impairs brain function when liver disease prevents its proper metabolism.
- The standard dosage for hepatic encephalopathy is 550 mg taken orally twice daily, and it is typically used as a long-term maintenance therapy to prevent recurrent episodes.
- Rifaximin is particularly valuable because it has minimal systemic absorption (less than 0.4%), which results in few side effects and a low risk of developing bacterial resistance.
- It is often used alongside lactulose, which works synergistically by acidifying the colon and trapping ammonia for elimination, providing more comprehensive management of hepatic encephalopathy, as recommended by recent guidelines 1.
Clinical Use
- Rifaximin has been shown to reduce the risk of recurrent hepatic encephalopathy by 58% compared to placebo, and also reduces the risk of readmissions and improves quality of life, as demonstrated in a recent study 1.
- The use of rifaximin as an adjunct to lactulose is recommended as secondary prophylaxis following more than one additional episode of overt hepatic encephalopathy within 6 months of the first one, according to recent guidelines 1.
From the FDA Drug Label
12.4 Microbiology Mechanism of Action Rifaximin is a semi-synthetic derivative of rifampin and acts by binding to the beta-subunit of bacterial DNA-dependent RNA polymerase blocking one of the steps in transcription. The FDA drug label does not answer the question of the mechanism of action of Rifaximin for encephalopathy.
From the Research
Rifaximin Mechanism of Action for Encephalopathy
- Rifaximin is a nonabsorbed derivative of rifamycin with a broad spectrum of activity against aerobic and anaerobic gram-positive and gram-negative organisms 2.
- The exact mechanism of action of rifaximin in the treatment of hepatic encephalopathy is not fully understood, but it is thought to be related to its ability to reduce the accumulation of ammonia and other gut-derived toxins 3.
- Rifaximin has been shown to be effective in improving behavioral, laboratory, mental status, and intellectual abnormalities associated with hepatic encephalopathy 4.
- The use of rifaximin has been compared to lactulose and neomycin, with rifaximin showing a general trend toward better efficacy and a better safety and tolerability profile 2.
Efficacy of Rifaximin
- Rifaximin has been shown to be effective in reducing the risk of an episode of hepatic encephalopathy, as well as the risk of hospitalization involving hepatic encephalopathy 5.
- Studies have demonstrated that rifaximin is at least equally effective as, and in some cases superior to, nonabsorbable disaccharides and antimicrobials in relieving signs or symptoms observed in patients with mild-to-moderately severe hepatic encephalopathy 4.
- Rifaximin has been found to be associated with fewer hospitalizations, fewer days of hospitalization, and lower hospitalization charges than lactulose 3.
Safety and Tolerability
- Rifaximin has been shown to be safe and well-tolerated for the treatment of minimal and overt hepatic encephalopathy, as well as for the maintenance of hepatic encephalopathy remission 6.
- The incidence of adverse events reported during studies of rifaximin has been similar to that of placebo, with mostly minor gastrointestinal complaints 5.
- Rifaximin has been found to have a better tolerance profile than comparative agents, such as lactulose and neomycin 3.