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Rifaximin Tablets (Xifaxan®)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San rancisco.
Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Editor Stephen A. Brunton, MD, is Adjunct Clinical Professor, University of North Carolina, Chapel Hill. Peer reviewer Gerald Roberts, MD, is Assistant Clinical Professor of Medicine, Albert Einstein College of Medicine, New York, NY.
Drs. Elliott, Chan, and Roberts report no financial relationships to this field of study. Dr. Brunton serves on the advisory boards of Amylin, Kova, and Novo Nordisk; he serves on the speaker's bureaus of Boehringer Ingelheim and Novo Nordisk.
This article originally appeared in the May 15, 2010 issue of Internal Medicine Alert.
A rifamycin antibacterial agent has been approved for treating patients with hepatic encephalopathy (HE). Rifaximin is a minimally absorbed oral antimicrobial that was originally approved in 2004 for the treatment of travelers' diarrhea caused by Escherichia coli. It is marketed by Salix Pharmaceuticals as Xifaxan®.
Rifaximin is indicated to reduce the risk of hepatic encephalopathy recurrence in adult patients who are in remission.1
The recommended dose is one 550 mg tablet twice daily. The drug may be taken with or without food. Rifaximin is available as 200 mg and 550 mg tablets.
Rifaximin reduces the risk of an episode of hepatic encephalopathy and the risk of hospitalization involving hepatic encephalopathy.1,2
More than 90% of study subjects in the clinical trial were using lactulose. The effectiveness of rifaximin is not known if given without lactulose. In the pivotal trial that led to the approval for this indication, 2 of 140 patients in the treatment group developed C. difficile infections as compared 0 of 159 patients in the control group.2
Rifaximin is an orally administered nonsystemic antibacterial agent. Its efficacy was shown in a double-blind, international, randomized, placebo-controlled trial in patients who had at least two episodes of hepatic encephalopathy in the previous 6 months but were in remission. Study participants were randomized to rifaximin (550 mg twice daily; n = 140) or placebo (n = 159) for 6 months. The incidence of HE was 22% in the rifaximin group and 46% in the placebo group (hazard ratio [HR] 0.42; 95% confidence interval [CI], 0.28-0.64; P < 0.001). The rates of hospitalization involving HE were 13.6% and 22.6%, respectively (HR 0.50; 95% CI, 0.29-0.87; P = 0.01). Ninety-one percent of subjects had concomitant therapy with lactulose. The incidence of adverse events was similar between the two groups; however, a higher frequency (compared to placebo) occurred for peripheral edema (15% vs 8%), dizziness (13% vs 8%), and anemia (8% vs 4%). The two patients who developed C. difficile infection continued rifaximin therapy along with concomitant treatment for the infection and fully recovered. Rifaximin has also been reported to be effective as acute treatment for HE compared to non-absorbable disaccharides and antibiotics.3,4
More than 5 million Americans have hepatic cirrhosis. Hepatic encephalopathy is a complication of hepatic cirrhosis that is severely debilitating and often results in hospitalization. It is characterized by cognitive deficit that can vary from mild lack of awareness to coma.5 The pathophysiology appears to be multifactorial, but ammonia produced by gut flora is most commonly implicated. Current therapy includes lactulose and oral antibiotics such as neomycin. Rifaximin is a nonsystemic antibacterial with broad-spectrum activity against gram-positive, gram-negative, and anaerobic enteric bacteria. It has been shown to reduce the risk of HE and hospitalization involving HE.