Rifaximin is a non-absorbable oral antibiotic. Rifaximin has a broad spectrum of activity against both gram-negative and gram-positive anaerobic and aerobic bacteria. This particular antibiotic is used primarily for gastrointestinal and liver diseases since it is specific to the gastroenterology tract due to its non-absorbable profile. 

Rifaximin was first approved in the United States in 2004 but has been in use since 1987 when it first received approval in Italy. In the United States, rifaximin is FDA approved for the treatment of irritable bowel syndrome (diarrhea type), treatment and prevention of hepatic encephalopathy in advanced liver disease, and treatment of traveler's diarrhea caused by non-invasive strains of E. coli. Off-label non-FDA approved indications for rifaximin are small intestinal bacterial overgrowth (SIBO), prevention of traveler's diarrhea, diverticulitis, pouchitis, inflammatory bowel disease, spontaneous bacterial peritonitis, and even Clostridium difficile.[1][2] 

There are many published studies regarding the efficacy of rifaximin in the treatment of diseases outside of those that are FDA-approved. 

Rifaximin is a synthetic antimicrobial derived from the parent compound, Rifamycin. It has broad-spectrum bactericidal activity against both gram-positive and gram-negative aerobic and anaerobic bacteria.[3] Rifaximin has also demonstrated an effect on enteric protozoa activity in HIV patients with Cryptosporidium parvum and Blastocystitis hominis intestinal infections. The medication acts on and inhibits the bacteria's ability to synthesize proteins. The drug accomplishes this by irreversibly binding to the bacterial DNA-dependent RNA polymerase called rpoB.[4]

Because rifaximin is non-absorbable, it reaches high concentrations within the gastrointestinal lumen, which allows it to work effectively on a variety of gastrointestinal diseases without systemic effects.[5] There is a very low incidence of bacterial mutation and drug resistance to rifaximin in extra-intestinal bacteria. However, long-term use of rifaximin can result in resistant bacterial mutants in the enteric system.[1] 

Rifaximin is administered as an oral tablet. Since it is poorly absorbed in the gastrointestinal system, there are very low systemic blood levels, and most of the medication passes through the gastrointestinal tract and is excreted in the feces. The dose regimens vary depending on the disease process for which the patient is receiving treatment.

For IBS-diarrhea, the suggested dose of rifaximin is 400 mg three times or 550 mg twice daily for two weeks. IBS-diarrhea may require intermittent rifaximin treatment. Typically in traveler's diarrhea, 200 mg three times daily is given for three days. For the prevention of traveler's diarrhea, the recommendation is to use rifaximin 200 mg twice daily or 600 mg daily during the time spent in areas at high risk for traveler's diarrhea.

Hepatic encephalopathy requires a dose of 550 mg twice or three times daily and is usually continued for an extended period to prevent its recurrence. Rifaximin is generally used in combination with lactulose in the treatment of hepatic encephalopathy. For small intestinal bacterial overgrowth, the typical dose of rifaximin is 400 mg three times daily for two weeks. Recurrent treatment may sometimes be warranted.

Studies show that rifaximin at a dose of 400 mg twice daily for seven days every month improves diverticular disease symptoms and prevents their recurrence. Pouchitis patients may need doses 400 to even 800 mg twice daily for 12 weeks; they may need intermittent retreatment. Recurrent Clostridium difficile treatment in retrospective studies and case series was 400 mg twice daily for two weeks. Spontaneous bacterial peritonitis prophylaxis should use rifaximin three times daily indefinitely.[1]

Rifaximin has an excellent safety profile due to its lack of systemic absorption. Clinical trials have shown that adverse effects of rifaximin are similar to or even lower frequency when compared to placebo, trimethoprim-sulfamethoxazole, and ciprofloxacin. Clinical trials did not show any serious adverse events while using rifaximin. There were no deaths while using rifaximin in clinical trials. Rifaximin does not require dose adjustments for hepatic dysfunction.[4]

There are published case reports of rifaximin interacting with warfarin, which resulted in reductions in INR levels. In vivo studies have previously shown that CYP3A4 can be induced by rifaximin, which can then affect the bioavailability of CYP3A4 substrates.[6] Although these studies have demonstrated that rifaximin can affect CYP3A4 enzyme activity, this would likely never happen in a patient because of the minimal systemic absorption.[7]

Due to the excellent safety profile of rifaximin, there are very few contraindications. Like all medications, patients that have hypersensitivity to the drug, class of antibiotics, or components of the tablet should avoid this medication.