What is the use of Rifaximin (Rifamycin derivative)?

From the Guidelines

Rifaximin is recommended as an add-on treatment to lactulose for the prevention of recurrent overt hepatic encephalopathy, as it has been shown to reduce the risk of recurrence by 58% compared to placebo 1.

Key Points

• Rifaximin works by inhibiting bacterial RNA synthesis and is minimally absorbed in the gut, allowing it to target intestinal bacteria while limiting systemic effects.
• The standard dose of rifaximin for hepatic encephalopathy is 550 mg twice daily for long-term management to prevent recurrence.
• Rifaximin has been shown to reduce the risk of readmissions and improve quality of life in patients with hepatic encephalopathy 1.
• The use of rifaximin alone in the prevention of recurrent overt hepatic encephalopathy is not recommended, as it is difficult to recommend its use without lactulose 1.

Considerations

• Rifaximin should be used cautiously in patients with severe liver impairment and is contraindicated in those with hypersensitivity to rifamycin antibiotics.
• Common side effects of rifaximin include nausea, bloating, and headache, though these are generally mild due to its limited absorption.
• The safety profile of rifaximin is excellent, with no indication of increased risk of developing antibiotic resistance or adverse events 1.

From the FDA Drug Label

2 micromolar. No significant induction of CYP3A4 enzyme using midazolam as a substrate was observed when rifaximin was administered three times a day for 7 days at 200 mg and 550 mg doses in two clinical drug interaction studies in healthy subjects The effect of XIFAXAN 200 mg administered orally every 8 hours for 3 days and for 7 days on the pharmacokinetics of a single dose of either 2 mg intravenous midazolam or 6 mg oral midazolam was evaluated in healthy subjects No significant difference was observed in the systemic exposure or elimination of intravenous or oral midazolam or its major metabolite, 1’-hydroxymidazolam, between midazolam alone or together with XIFAXAN. Therefore, XIFAXAN was not shown to significantly affect intestinal or hepatic CYP3A4 activity for the 200 mg three times a day dosing regimen When a single dose of 2 mg midazolam was orally administered after administration of XIFAXAN 550 mg three times a day for 7 days and 14 days to healthy subjects, the mean AUC of midazolam was 3.8% and 8. 8% lower, respectively, than when midazolam was administered alone. The mean Cmax of midazolam was lower by 4 to 5% when XIFAXAN was administered for 7-14 days prior to midazolam administration. This degree of interaction is not considered clinically meaningful

Rifaximin does not significantly affect intestinal or hepatic CYP3A4 activity for the 200 mg three times a day dosing regimen.

• The mean AUC of midazolam was 3.8% and 8.8% lower when XIFAXAN 550 mg was administered for 7 and 14 days, respectively.
• The mean Cmax of midazolam was lower by 4 to 5% when XIFAXAN was administered for 7-14 days prior to midazolam administration. This degree of interaction is not considered clinically meaningful 2.

From the Research

Rifaximin Overview

• Rifaximin is a nonabsorbed oral antibiotic with antimicrobial activity against Gram-positive and Gram-negative aerobic and anaerobic bacteria 3.
• It has been shown to be effective in the treatment of various gastrointestinal and liver diseases, including traveler's diarrhea, functional bloating, irritable bowel syndrome, small bowel bacterial overgrowth, and hepatic encephalopathy 4, 3, 5, 6, 7.

Therapeutic Uses

• Rifaximin has been approved for the treatment of traveler's diarrhea and hepatic encephalopathy 4, 6, 7.
• It has also been shown to be effective in the treatment of irritable bowel syndrome, particularly in reducing global IBS symptoms and improving bloating, abdominal pain, and stool consistency 5.
• Additionally, rifaximin may be beneficial in the treatment of uncomplicated diverticular disease and the prevention of recurrent diverticulitis 3.

Safety and Efficacy

• Rifaximin has a good tolerability profile and is associated with a low incidence of adverse effects 4, 3, 5, 6, 7.
• The development of bacterial resistance to rifaximin is unlikely due to its minimal systemic absorption and limited cross-resistance with other antimicrobials 3, 7.
• Rifaximin has been shown to be at least as effective as other treatments, such as lactulose/lactitol and ciprofloxacin, in reducing the duration of illness and restoring wellbeing in patients with traveler's diarrhea and hepatic encephalopathy 4, 7.