title: Rifaximin: new therapeutic indication and future directions.
abstract: BACKGROUND
  Rifaximin is a nonabsorbable oral antibiotic that acts locally in the gastrointestinal tract with minimal systemic adverse effects. Rifaximin received new labeling for reduction in the risk of the recurrence of overt hepatic encephalopathy (HE) in patients with advanced liver disease in March of 2010.
  
  
  OBJECTIVE
  This article reviews the pharmacology, pharmacokinetics, and pharmacodynamics of rifaximin. The efficacy and safety of rifaximin in reducing the risk of the recurrence of overt HE in patients with advanced liver disease, the new US Food and Drug Administration-approved indication, is the focus of this review. Emerging data on the use of rifaximin in irritable bowel syndrome (IBS) and Clostridium difficile infection (CDI) are also evaluated.
  
  
  METHODS
  MEDLINE and International Pharmaceutical Abstracts from 1983 to January 31, 2011, were searched using the key terms rifaximin, L/105, secondary hepatic encephalopathy, irritable bowel syndrome, and Clostridium difficile. Ongoing trials were identified using the clinicaltrials.gov Web site. Abstracts from the annual meetings of the American College of Gastroenterology and Digestive Disease Week from 2004 to 2010 and references from relevant articles were reviewed. Only trials examining use of rifaximin in secondary prophylaxis of HE were included. Studies on the efficacy and safety of rifaximin in the treatment of acute episodes of HE have been recently summarized elsewhere and are not reviewed here.
  
  
  RESULTS
  Literature search identified one trial on rifaximin use in secondary prevention of HE, six trials in patients with IBS, and six small studies and case reports in patients with CDI. In a trial of 299 patients, use of rifaximin 550 mg by mouth twice daily for 6 months for prevention of recurrent HE was associated with significantly fewer breakthrough HE episodes compared with placebo (rifaximin 22%, placebo 46%; P < 0.001), with a hazard ratio of 0.42 (95% CI, 0.28-0.64). The rifaximin group also had fewer hospitalizations involving HE compared with placebo (rifaximin 13.6%, placebo 22.6%; P = 0.01), with a hazard ratio of 0.50 (95% CI, 0.29-0.87). Rifaximin improved IBS symptom management in ∼9% more patients than placebo in 2 prospective, randomized, double-blind, placebo-controlled trials of 1260 patients (in the rifaximin group, 40.8% patients reported IBS symptom improvement compared with 31.7% in the placebo group; P < 0.001). The efficacy of rifaximin has been reported for the treatment of refractory or recurrent CDI in small studies, case series, and a case report. Optimal dosing, duration, and role of rifaximin for CDI management is unclear. In clinical trials of rifaximin for prevention of recurrent HE and for nonconstipated IBS, its safety profile was comparable to placebo. In the trial of rifaximin for prevention of recurrent HE, the most common adverse events occurring in 10% to 15% of patients were ascites, dizziness, fatigue, and peripheral edema. Most common adverse effects in IBS trials included abdominal pain, diarrhea, bad taste, headache, and upper respiratory tract infection, occurring in <10% of patients.
  
  
  CONCLUSIONS
  Rifaximin can be an effective option for reduction in the risk of the recurrence of HE in patients with advanced liver disease. Studies suggest that rifaximin provides relief of global symptoms of diarrhea-predominant IBS and bloating. Use of rifaximin in CDI requires further study.
authors: Pharmacy Practice, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, New York, USA.
authors: Anastasia
authors: A
authors: Rivkin
authors: Suzanna
authors: S
authors: Gim
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016360:Clostridioides difficile / Q000302:isolation & purification; D003015:Clostridium Infections / Q000188:drug therapy; D006501:Hepatic Encephalopathy / Q000188:drug therapy* / Q000517:prevention & control; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000188:drug therapy; D012294:Rifamycins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000078262:Rifaximin; D055502:Secondary Prevention
chemical_list: D000890:Anti-Infective Agents; D012294:Rifamycins; D000078262:Rifaximin