The Food and Drug Administration has approved rifaximin (Xifaxan), a nonsystemic antibiotic, for the prevention of recurrent hepatic encephalopathy in patients 18 years of age or older with liver disease. Structurally similar to the antituberculosis drug rifampin (Rifadin), rifaximin binds to a β-subunit of bacterial DNA–dependent RNA polymerase, thereby preventing bacterial RNA synthesis. It's been found to be effective against Escherichia coli in infectious diarrhea and was therefore already approved for use in treating traveler's diarrhea. Because rifaximin also lowers levels of ammonia in the blood, it's believed to be effective in decreasing the risk of recurrent hepatic encephalopathy in patients with advanced liver disease.
The efficacy of rifaximin for this indication was evaluated in a placebo-controlled, double-blind, multicenter trial (published in the March 25 issue of the New England Journal of Medicine) that randomly assigned patients in remission from hepatic encephalopathy to receive rifaximin (550 mg twice daily) or placebo for six months. Most patients were also taking the standard treatment of lactulose (a synthetic sugar that prevents absorption of ammonia from the gastrointestinal [GI] tract). Over the treatment period, rifaximin significantly reduced the risk of hepatic encephalopathy episodes compared with placebo (22.1% of patients in the rifaximin group experienced a breakthrough episode compared with 45.9% in the placebo group). Treatment also reduced the risk of hospitalization for hepatic encephalopathy.
Because rifaximin alone hasn't been tested in a sufficient number of patients to determine its therapeutic effectiveness as monotherapy, it shouldn't be administered alone. It also hasn't been tested in patients with severe disease (scores higher than 25 out of 40 on the Model for End-Stage Liver Disease [MELD] scale) or in patients under the age of 18.
Rifaximin is administered orally. The dose for preventing hepatic encephalopathy is higher, but the number of daily doses is less, than that prescribed for traveler's diarrhea (550 mg twice a day, compared with 200 mg three times a day for three days, respectively). The most common adverse effects associated with rifaximin use are peripheral edema, nausea, gas, and headache. Nurses should monitor patients with hepatic impairment who are started on rifaximin very closely because they may be more likely to experience systemic adverse effects from the drug in addition to the expected localized effects within the GI tract.