HONOLULU — Rifaximin is the new treatment of choice for patients with hepatic encephalopathy, Dr. Carroll B. Leevy said at the annual meeting of the American College of Gastroenterology.
Rifaximin (Xifaxan), a nonabsorbable antibiotic with gastrointestinal specificity approved by the Food and Drug Administration for treating travelers' diarrhea, is approved in 17 other countries for management of hepatic encephalopathy.
Rifaximin proved superior to lactulose, the current standard therapy, in a single-center retrospective crossover study. Rifaximin resulted in less hospitalization and lower hospital costs than lactulose, and maintained patients at less severe grades of hepatic encephalopathy, said Dr. Leevy, clinical affairs director at the New Jersey Medical School Liver Center, Newark.
Hepatic encephalopathy is characterized by altered mental status. Hospitalizations for the disease tend to be prolonged, lasting a mean of 5–7 days and costing $23,000 per episode.
The disorder is due to systemic accumulation of ammonia, which is not detoxified in the cirrhotic liver. Rifaximin is thought to reduce ammoniagenic bacteria in the gut. Neomycin and other antibiotics also have been reported to be effective in hepatic encephalopathy, but with more toxicity due to systemic absorption.
Dr. Leevy reported on 145 patients with hepatic encephalopathy who received 30 cc b.i.d. of lactulose for 6 months or longer, then were switched to rifaximin at 400 mg t.i.d. for at least 6 months. He compared end points during the patients' last 6 months on lactulose with those during their first 6 months on rifaximin. All key end points were significantly better in the rifaximin group. (See box below.)
Most patients on lactulose were in hepatic encephalopathy grade 2 (lethargy, obvious personality changes, and/or inappropriate behavior) or grade 3 (disoriented as to time and place, and with incomprehensible speech) versus grade 1 or 2 while on rifaximin.
Compliance was significantly better with rifaximin as well. Most patients took 50%–75% of their doses of lactulose, as compared with 75%–100% of their three times daily doses of rifaximin, he added.
One audience member defended lactulose as a trusted drug and said he wasn't about to discard it based on a single-center retrospective study. Dr. Leevy said that the problem with lactulose isn't whether it can be efficacious but “that it's hard to tolerate and few people will take it.” Most patients experience diarrhea or constipation as a side effect, which worsens their hepatic encephalopathy, he said.
Dr. Leevy said that Salix Pharmaceuticals Inc., rifaximin's maker, paid for the statistical analysis; the study itself was initiated and funded by the hospital.