Rifaximin ( Normix, Xifaxan ) is a gut-selective, oral antimicrobial agent shown to reduce the recurrence of overt hepatic encephalopathy ( HE) and HE-related hospitalizations in a 6-month, randomized, controlled trial ( RCT ).
Researchers have performed a phase 3, open-label maintenance study to assess the safety and rate of hospitalization with long-term Rifaximin use.
It was conducted a 24-month, open-label maintenance study of Rifaximin ( 550 mg, twice daily ) in patients with hepatic encephalopathy who participated in the previous RCT of Rifaximin or new patients enrolled during the period 2007-2010.
Safety was assessed ( adverse events, clinical laboratory parameters ) for the integrated population of all patients, who were given Rifaximin 550 mg twice daily ( all-Rifaximin population, n=392 ). Safety and hospitalization data were compared between the group given placebo in the original RCT ( n=159 ) and those given Rifaximin ( n=140 ).
In the all-Rifaximin population, the median exposure to Rifaximin was 427.0 days ( range, 2-1427 days ), with 510.5 person-years of exposure.
The profile and rate of adverse events with long-term Rifaximin treatment were similar to those of the original RCT. There was no increase in the rate of infections, including with Clostridium difficile, or development of bacterial antibiotic resistance.
Rates of hospitalizations with long-term Rifaximin administration remained low: the hepatic encephalopathy-related hospitalization rate, normalized for exposure ( 0.21; all-Rifaximin population ), was similar to that of the Rifaximin group in the original RCT ( 0.30 ), and lower than that for the placebo group ( 0.72 ).
In conclusion, long-term treatment ( greater than or equal to 24 months ) with Rifaximin ( 550 mg, twice daily ) appears to provide a continued reduction in the rate of hepatic encephalopathy-related and all-cause hospitalization, without an increased rate of adverse events. ( Xagena )
Mullen KD et al, Clin Gastroenterol Hepatol 2013; Epub ahead of print