title: Rifaximin is safe and well tolerated for long-term maintenance of remission from overt hepatic encephalopathy.
abstract: OBJECTIVE
  Rifaximin is a gut-selective, oral antimicrobial agent shown to reduce the recurrence of overt hepatic encephalopathy (HE) and HE-related hospitalizations in a 6-month, randomized, controlled trial (RCT). We performed a phase 3, open-label maintenance study to assess the safety and rate of hospitalization with long-term rifaximin use.
  
  
  METHODS
  We conducted a 24-month, open-label maintenance study of rifaximin (550 mg, twice daily) in patients with HE who participated in the previous RCT of rifaximin or new patients enrolled from March 2007 to December 2010. Safety was assessed (adverse events, clinical laboratory parameters) for the integrated population of all patients, who were given rifaximin 550 mg twice daily (all-rifaximin population, N = 392). Safety and hospitalization data were compared between the group given placebo in the original RCT (n = 159) and those given rifaximin (n = 140).
  
  
  RESULTS
  In the all-rifaximin population, the median exposure to rifaximin was 427.0 days (range, 2-1427 d), with 510.5 person-years of exposure. The profile and rate of adverse events with long-term rifaximin treatment were similar to those of the original RCT. There was no increase in the rate of infections, including with Clostridium difficile, or development of bacterial antibiotic resistance. Rates of hospitalizations with long-term rifaximin administration remained low: the HE-related hospitalization rate, normalized for exposure (0.21; all-rifaximin population), was similar to that of the rifaximin group in the original RCT (0.30), and lower than that for the placebo group (0.72).
  
  
  CONCLUSIONS
  Long-term treatment (≥24 mo) with rifaximin (550 mg, twice daily) appears to provide a continued reduction in the rate of HE-related and all-cause hospitalization, without an increased rate of adverse events. ClinicalTrials.gov number: NCT00686920.
authors.affiliation: Case Western Reserve University School of Medicine, Cleveland, Ohio. Electronic address: kdm@case.edu.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Mullen
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Arun J
authors.initials: AJ
authors.lastname: Sanyal
authors.affiliation: Divison of Gastroenterology, University of California San Francisco, San Francisco, California.
authors.forename: Nathan M
authors.initials: NM
authors.lastname: Bass
authors.affiliation: The Texas Liver Institute/University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Fred F
authors.initials: FF
authors.lastname: Poordad
authors.affiliation: University of California San Francisco Fresno Medical Education Program, Fresno, California.
authors.forename: Muhammad Y
authors.initials: MY
authors.lastname: Sheikh
authors.affiliation: Division of Hepatology, California Pacific Medical Center, San Francisco, California.
authors.forename: R Todd
authors.initials: RT
authors.lastname: Frederick
authors.affiliation: Salix Pharmaceuticals, Inc, Raleigh, North Carolina.
authors.forename: Enoch
authors.initials: E
authors.lastname: Bortey
authors.affiliation: Salix Pharmaceuticals, Inc, Raleigh, North Carolina.
authors.forename: William P
authors.initials: WP
authors.lastname: Forbes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D006501:Hepatic Encephalopathy / Q000188:drug therapy*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D012294:Rifamycins / Q000009:adverse effects* / Q000627:therapeutic use*; D000078262:Rifaximin; D055815:Young Adult
chemical_list: D005765:Gastrointestinal Agents; D010919:Placebos; D012294:Rifamycins; D000078262:Rifaximin
keywords: Antimicrobial Agent; Chronic Liver Disease; Cirrhosis; Xifaxan