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RACHEL TAVARES DE MELO, PHARM.D., is Solid Organ Transplant Pharmacy Resident, New York-Presbyterian Hospital, The University Hospital of Columbia and Cornell, New York. LISA CHARNESKI, PHARM.D., BCPS, is Assistant Professor, Department of Pharmacy Practice and Science, University of Maryland, Rockville. OLGA HILAS, PHARM.D., BCPS, CGP, is Assistant Clinical Professor of Clinical Pharmacy Practice, College of Pharmacy and Allied Health Professions, St. John’s University, Queens, NY, and Clinical Coordinator of Internal Medicine/Geriatrics, New York-Presbyterian Hospital, Weill Cornell Medical Center, New York.

Address correspondence to Dr. Charneski at the Department of Pharmacy Practice and Science, University of Maryland, 9640 Gudelsky Drive, Building I, Room 304, Rockville, MD 20850 (lcharnes{at}rx.umaryland.edu).

Purpose. The use of rifaximin for the treatment of hepatic encephalopathy (HE) is reviewed. Summary. HE is observed in approximately 50–70% of all patients with cirrhosis. Clinical manifestations of HE range from altered mental status to deep coma. Most manifestations of this syndrome are reversible with medical treatment. Treatment measures focus on the resolution of ammonia accumulation and identification/ removal of precipitating factors. Lactulose has been the mainstay of HE treatment in the acute and chronic settings, though its use is limited by poor patient tolerance and compliance. Chronic administration of antibiotics has also proven to be effective in HE. Historically, neomycin or metronidazole has been used, but both carry the risk of serious adverse effects. Rifaximin is a nonabsorbed derivative of rifamycin with a broad spectrum of activity against aerobic and anaerobic gram-positive and gram-negative organisms. Clinical trials have compared rifaximin to lactulose or neomycin for the treatment of HE. Rifaximin shows a general trend toward better efficacy versus lactulose or neomycin. In addition, rifaximin seems to offer a better safety and tolerability profile than that of lactulose and possibly neomycin. Conclusion. While no randomized, placebo-controlled studies have assessed the efficacy and long-term safety outcomes of rifaximin in the treatment of HE, rifaximin has demonstrated better efficacy and safety profiles compared with lactulose and neomycin. Future studies should assess HE outcomes with more consistent indexes and measurements and should compare the efficacy and safety of rifaximin with those of metronidazole. Index terms: Antiinfective agents; Hepatic encephalopathy; Mechanism of action; Rifaximin; Toxicity