The primary end point was the time to first breakthrough overt hepatic encephalopathy episode, defined as an increase of the Conn score to a 2 or higher, or an increase in the Conn score and Asterixis grade of 1 each among those with a baseline Conn score of 0.
The active drug also reduced the relative risk for hospitalization by 50%. Hospitalization involving hepatic encephalopathy was reported for 13.6% of patients on rifaximin and 22.6% of those on placebo.
Mortality was 6% (9 of 140) with rifaximin and 7% (11 of 159) with placebo; deaths were due mostly to worsening hepatic function and progression of the underlying disease.
Since the drug was approved more than 5 years ago for traveler's diarrhea, there have been five postmarketing reports of C. difficile colitis associated with rifaximin treatment, including one death, according to the FDA.
In addition, anaphylaxis has been identified as a notable adverse effect in postmarketing reports, and this risk is now included in the drug's label.
“These data suggest that four patients would need to be treated with rifaximin for 6 months to prevent one episode of overt hepatic encephalopathy,” Dr. Bass and his colleagues said. First approved in Italy in 1985, rifaximin is now approved in 33 countries for various GI uses, including hepatic encephalopathy and adjunctive treatment of hyperammonemia, according to the manufacturer.
Disclosures: The study was supported by Salix Pharmaceuticals. Dr. Bass reported receiving consulting, advisory, and lecture fees from Salix. Members of FDA advisory panels have been cleared for potential conflicts of interest related to the topic under review prior to the meeting.
My Take
Try Lactulose, Then Rifaximin
Hepatic encephalopathy, a frequent complication for patients with cirrhosis, results in disability that is generally recognized as episodes of overt confusion. Minimal hepatic encephalopathy from cirrhosis may be more difficult to recognize, because it produces less-overt complications such as impaired driving and automobile accidents.
Lactulose, a nonabsorbable disaccharide that alters colonic pH and bowel frequency, has been the mainstay of therapy for hepatic encephalopathy, although the laxative effect of lactulose can be a problem for some patients. Rifaximin, an antibiotic with limited absorption, reduces the frequency of episodes of hepatic encephalopathy in patients with cirrhosis and thus offers another therapeutic option.
Given the associated cost savings, I typically use lactulose as first-line therapy for most patients with hepatic encephalopathy, and reserve rifaximin for those who are poorly controlled or who develop significant GI side effects from lactulose.
ROWEN K. ZETTERMAN, M.D., a gastroenterologist, is dean of the school of medicine at Creighton University, Omaha, Neb. He reported no relevant conflicts of interest.
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