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New indication: Rifaximin (Xifaxan) was approved in March 2010 for the reduction in risk of overt hepatic encephalopathy recurrence in patients ≥18 years of age.
Rifaximin 550-mg tablets were approved by FDA in March 2010, to reduce the risk of recurrent overt hepatic encephalopathy in patients ≥18 years of age. Hepatic encephalopathy is a worsening of brain function (including confusion, altered level of consciousness, and coma) that can occur in patients whose liver can no longer remove nitrogenous waste from their bloodstreams. Increased levels of ammonia are thought to play a role in the development of hepatic encephalopathy. Rifaximin, an antibacterial agent, kills off intestinal bacteria responsible for the generation and conversion of nitrogenous waste to ammonia. Consequently, it can reduce ammonia levels in the bloodstream.
Efficacy. Rifaximin's efficacy in hepatic encephalopathy was established in a clinical trial of adult patients from the United States, Canada, and Russia. This study was recently published in the March 25, 2010 edition of the New England Journal of Medicine. In this randomized, double-blind, placebo-controlled trial, 299 patients who were in remission (no or mild symptoms) from recurrent hepatic encephalopathy due to chronic liver disease were randomly assigned to receive either rifaximin, at a dose of 550 mg twice daily (n=140 patients), or placebo (n=159 patients) for 6 months. Rifaximin significantly reduced the risk of having an episode of hepatic encephalopathy, as compared with placebo (HR=0.42 with rifaximin; 95% CI, 0.28 to 0.64; P<.001). Furthermore, a total of 13.6% of patients in the rifaximin group had a hospitalization involving hepatic encephalopathy, as compared with 22.6% of patients in the placebo group, representing a hazard ratio of 0.50 (95% CI, 0.29 to 0.87; P=.01). Since most patients (more than 90%) were also taking the gold-standard lactulose for the treatment of hepatic encephalopathy (a synthetic sugar, which helps prevent absorption of ammonia from the intestine) during the trial, the efficacy of rifaximin as a stand-alone treatment could not be assessed.
Safety. The incidence of adverse events reported during the above-mentioned clinical trial was similar in the rifaximin and placebo groups, as was the incidence of the more common serious adverse events. Adverse events reported in the prescribing information to occur in >10% of rifaximin-treated patients and more often than placebo include nausea (14%), fatigue (12%), peripheral edema (15%), ascites (11%), and dizziness (13%). Moreover, treatment with antibacterial agents such as rifamixin alters the normal flora of the colon, which may lead to overgrowth of Clostridium difficile. C. difficile-associated diarrhea has been reported with use of rifaximin, and may range in severity from mild diarrhea to fatal colitis.