Background: Rifaximin 550 mg tablets is a nonsystemic antibiotic indicated for reducing the risk of overt hepatic encephalopathy (OHE) recurrence in adults and may be used alone or in combination with the cathartic lactulose. This analysis evaluated the safety profile of rifaximin alone vs rifaximin + lactulose (combination) in patients with cirrhosis.
Methods: In a phase 4, randomized, open-label trial, adults with cirrhosis and a history of ≥1 OHE episode during the prior 6 months who are currently in HE remission (Conn score ≤1) received rifaximin 550 mg twice daily (BID) or rifaximin 550 mg BID + lactulose (titrated; 2-3 soft stools/d) for 24 wks. Patients receiving ≥1 dose of study drug were included in the safety analysis.
Results: Overall, 221 patients received rifaximin alone (n=113) or rifaximin + lactulose combination (n=108). For rifaximin alone vs combination, the mean age (standard deviation [SD]) was 58.1 (9.5) vs 58.8 (9.5) years; patients aged ≥65 years were 22.1% vs 29.6%; male patients were 61.1% vs 64.8%; and the mean Model End Stage Liver Disease score (SD) was 11.9 (3.6) vs 11.8 (3.2). Six (5.3%) patients in the rifaximin alone group and 14 (13.0%) in the combination group had drug-related adverse events (AEs). These AEs were mostly gastrointestinal (GI) tract–related. There was an apparent trend for drug-related GI AEs to be more frequently reported in the combination group vs the rifaximin alone group (diarrhea, 3.7% vs 0%; abdominal distension, 2.8% vs 0%; nausea, 2.8% vs 0%; abdominal pain, 1.9% vs 0.9%; abdominal discomfort, 0.9% vs 0%; flatulence, 0.9% vs 0%). No Clostridium difficile infections were reported during the study. Discontinuations due to any AE (excluding HE or liver transplant) were similar for the rifaximin alone (5.3%) and combination (3.7%) groups. Two deaths were reported in each group, and none were considered by the investigator to be treatment-related.
Conclusions: Rifaximin alone and rifaximin +lactulose combination therapy were both generally well tolerated as daily therapy to prevent OHE recurrence. The difference in the GI AE profile, favoring rifaximin alone, may be related to the commonly known adverse effects associated with lactulose.Support provided by Salix Pharmaceuticals.