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Abstract

Objective:

To evaluate the efficacy of rifaximin for the treatment of hepatic encephalopathy (HE).

Data Sources:

All articles were accessed via PubMed (January 1960–December 2008), Cochrane Library, and Iowa Drug Information Service (1966–December 2008) using the terms rifaximin and hepatic encephalopathy. In addition, reference citations from publications identified were reviewed.

Study Selection and Data Extraction:

All articles in English identified from the data sources were evaluated. Fifteen studies that evaluated the efficacy, safety, and/or cost-effectiveness of rifaximin for the treatment of HE are reviewed in this article.

Data Synthesis:

HE is a neuropsychiatric syndrome that develops in patients with acute or chronic liver failure. There are a number of accepted theories explaining the pathophysiology of HE. Currently, pharmacologic therapies include nonabsorbable disaccharides (lactulose) and antibiotics (neomycin and metronidazole). Recent studies have shown a possible benefit with a newer, nonabsorbable rifamycin derivative, rifaximin. It has a broad spectrum of activity against aerobic and anaerobic gram-positive and gram-negative organism. Clinical trials have compared rifaximin with lactulose, neomycin, or metronidazole for the treatment of HE. There have also been review articles addressing the cost-effectiveness of rifaximin compared with lactulose, including the cost of hospitalization. To date there have been no randomized, placebo-controlled studies that have assessed the efficacy and long-term safety outcomes of rifaximin in the treatment of HE; however, rifaximin has demonstrated similar efficacy and better safety profiles compared with other therapies, in particular, neomycin and lactulose.

Conclusions:

Patients with HE who are refractory to lactulose therapy or who have decreased tolerability to lactulose therapy may benefit from rifaximin as either adjunct therapy or salvage therapy.

ACPE Universal Program Numbers:

407-000-09-053-H01-P (Pharmacists); 407-000-09-053-H01-T (Technicians)

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References

Riordan

Williams

. Treatment of hepatic encephalopathy. N Engl J Med 1997; 337: 473–9.

Mas

Rodes

Sunyer

. Comparison of rifaximin and lactitol in the treatment of acute hepatic encephalopathy: Results of a randomized, double-blind, double-dummy, controlled clinical trial. J Hepatol 2003; 38: 51–8.

Parini

Cipolla

Ronchi

. Effect of rifaximin and paromomycin in the treatment of portal-systemic encephalopathy. Curr Ther Res 1992; 52: 34–9.

Tarao

Ikeda

Hayashi

. A successful use of vancomycin hydrochloride in the treatment of lactulose-resistant chronic hepatic encephalopathy. Gut 1990; 31: 702–6.

Als-Nielsen

Gluud

. Nonabsorbable disaccharides for hepatic encephalopathy: Systematic review of randomized trials. BMJ 2004; 328: 1046–52.

Als-Nielsen

Gluud

. Nonabsorbable disaccharides for hepatic encephalopathy. Cochrane Database Syst Rev 2004:CD003044. DOI 10.1002/14651858.CD003044.pub2

Adachi

Dupont

. Rifaximin: A novel non-absorbed rifamycin for gastrointestinal disorders. Clin Infect Dis 2006; 42: 541–7.

Zeneroli

Avallone

Corsi

Venturini

Baraldi

. Management of hepatic encephalopathy: Role of rifaximin. Chemotherapy 2005; 51: 90–5.

Lawrence

Klee

. Rifaximin for the treatment of hepatic encephalopathy. Pharmacother 2008; 28: 1019–32.

10.

Festi

Mazzella

Orsini

. Rifaximin in the treatment of chronic hepatic encephalopathy; results of a multicenter study of efficacy and safety. Curr Ther Res 1993; 54: 598–609.

11.

Williams

James

Warnes

. Evaluation of the efficacy and safety of rifaximin in the treatment of hepatic encephalopathy: A double-blind, randomized, dose-finding multi-center study. Eur J Gastroenterol Hepatol 2000; 12: 203–8.

12.

Sama

Moreslli-Labate

Pianta

. Clinical effects of rifaximin in patients with encephalopathy intolerant or non-responsive to previous lactulose treatment: An open-label, pilot study. Curr Ther Res 2004; 65: 413–22.

13.

Blei

Cordoba

. Hepatic encephalopathy. Am J Gastroenterol 2001; 96: 1968–76.

14.

Bass

. Review article: The current pharmacological therapies for hepatic encephalopathy. Aliment Pharmacol Ther 2006; 25: 23–31.

15.

Pedretti

Calzetti

Missale

. Rifaximin versus neomycin on hyperammoniemia in chronic portal systemic encephalopathy of cirrhotics. A double-blind randomized trial. Ital J Gastroenterol 1992; 24: 14–6.

16.

Miglio

Valpiani

Rossellini

Ferrieri

. Rifaximin, a non-absorbable rifamycin, for the treatment of hepatic encephalopahy. A double-blind randomized trial. Curr Med Res Opin 1997; 13: 593–601.

17.

Massa

Vallerino

Dodero

. Treatment of hepatic encephalopathy with rifaximin: Double blind, double dummy study versus lactulose. Eur J Clin Res 1993; 4: 7–18.

18.

Bucci

Plamieri

. Double-blind, double dummy comparison between treatment with rifaximin and lactulose in patients with medium to severe degree hepatic encephalopathy. Curr Med Res Opin 1993; 13: 109–18.

19.

Fera

Agostinacchio

Nigro

. Rifaximin in the treatment of hepatic encephalopathy. Eur J Clin Res 1993; 4: 57–66.

20.

Paik

Lee

Han

. Comparison of rifaximin and lactulose for the treatment of hepatic encephalopathy: A prospective randomized study. Yonsei Med J 2005; 46: 399–407.

21.

Puxeddu

Quartini

Massimetti

Ferrieri

. Rifaximin in the treatment of chronic hepatic encephalopathy. Curr Med Res Opin. 1995; 13: 274–81.

22.

Leevy

Phillips

. Hospitalizations during the use of rifaximin versus lactulose for the treatment of hepatic encephalopathy. Dig Dis Sci 2007; 52: 737–41.

23.

Neff

Kemmer

Zacharias

. Analysis of hospitalizations comparing rifaximin versus lactulose in the management of hepatic encephalopathy. Transplant Proc 2006; 38: 3552–5.

24.

Huang

Esrailian

Spiegel

BMR

. The cost-effectiveness and budget impact of competing therapies in hepatic encephalopathy—a decision analysis. Aliment Pharmacol Ther 2007; 26: 1147–61.

Rifaximin for Hepatic Encephalopathy