From the Guidelines
Rifaximin is recommended as an add-on therapy 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.
Indications and Dosage
- For hepatic encephalopathy, the standard dose is 550 mg twice daily for maintenance therapy to prevent recurrence.
- For traveler's diarrhea, the typical dose is 200 mg three times daily for 3 days.
- For irritable bowel syndrome with diarrhea (IBS-D), patients usually take 550 mg three times daily for 14 days, with potential retreatment for recurrence.
Mechanism of Action
Rifaximin works by inhibiting bacterial RNA synthesis and is minimally absorbed from the intestine, allowing it to target gut bacteria while limiting systemic effects.
Side Effects and Precautions
Common side effects include nausea, bloating, and headache, though these are generally mild. Rifaximin should be used cautiously in patients with severe liver impairment and is contraindicated in those with hypersensitivity to rifamycin antibiotics.
Efficacy and Safety
The use of rifaximin has been shown to be effective in reducing the risk of recurrent hepatic encephalopathy, with a good safety profile 1. However, the efficacy and safety of rifaximin in other indications, such as IBS-D and traveler's diarrhea, may vary depending on the specific context and patient population 1.
Key Considerations
- Rifaximin should be used in combination with lactulose for the prevention of recurrent overt hepatic encephalopathy.
- The use of rifaximin in other indications, such as IBS-D and traveler's diarrhea, should be guided by the specific clinical context and patient population.
- Patients with severe liver impairment or hypersensitivity to rifamycin antibiotics should be cautious when using rifaximin.
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.
Rifaximin is a semi-synthetic derivative of rifampin and acts by binding to the beta-subunit of bacterial DNA-dependent RNA polymerase blocking one of the steps in transcription.
- The mechanism of action of rifaximin results in inhibition of bacterial protein synthesis and consequently inhibits the growth of bacteria.
- Resistance to rifaximin is caused primarily by mutations in the rpoB gene.
- Antibacterial activity of rifaximin has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections.
- Cross-resistance between rifaximin and other classes of antimicrobials has not been observed. The clinical relevance of the Cmax and AUC reductions in the presence of rifaximin is not known 2.
From the Research
Rifaximin Overview
- Rifaximin is a nonabsorbed oral antibiotic with antimicrobial activity against enteric pathogens for gastrointestinal infections 3.
- It has been used to treat hepatic encephalopathy, travelers' diarrhea, and other conditions involving enteric bacteria.
Efficacy in Hepatic Encephalopathy
- Rifaximin has been shown to be at least as effective as lactulose/lactitol and neomycin and paromomycin in improving neurologic signs and symptoms and reducing blood ammonia levels in patients with hepatic encephalopathy 3.
- The addition of rifaximin to lactulose therapy has been found to reduce the risk and duration of hospitalizations for hepatic encephalopathy 4.
Efficacy in Travelers' Diarrhea
- Rifaximin has been found to be superior to placebo or loperamide and at least as effective as ciprofloxacin in reducing the duration of illness and restoring wellbeing in patients with travelers' diarrhea 5, 6.
- Rifaximin has been shown to be effective in treating travelers' diarrhea with and without identification of a pathogen, as well as in diarrhea caused by Escherichia coli infection 5, 7.