What is Rifaximin and How Does It Work?
Rifaximin, sold under the brand name Xifaxan, is a prescription antibiotic belonging to the rifamycin class of drugs. Its primary mechanism of action involves inhibiting bacterial RNA synthesis by binding to the beta-subunit of bacterial DNA-dependent RNA polymerase. This action stops bacteria from producing the proteins they need to survive, thereby preventing their growth and spread.
A key characteristic of rifaximin is that it is minimally absorbed into the bloodstream, with less than 0.4% entering systemic circulation. This means it acts almost exclusively within the gastrointestinal (GI) tract, which enhances its safety profile and reduces the likelihood of systemic side effects and drug interactions. Because of this gut-selective nature, it is used primarily for gastrointestinal and liver diseases. Beyond its direct antibacterial effects, rifaximin is also thought to modulate the gut microenvironment, reduce bacterial virulence, prevent bacterial translocation across the gut lining, and exert anti-inflammatory effects.
FDA-Approved Indications
The U.S. Food and Drug Administration (FDA) has approved rifaximin for three specific conditions:
- Irritable Bowel Syndrome with Diarrhea (IBS-D): For adults, rifaximin may be prescribed to provide relief from symptoms like abdominal pain and diarrhea. If symptoms return, treatment may be repeated. Studies have shown that rifaximin provides significantly more symptom relief compared to a placebo.
- Traveler's Diarrhea: Rifaximin is used to treat traveler's diarrhea caused by noninvasive strains of Escherichia coli (E. coli) in adults and children 12 years and older. It is important to note that it is not effective for diarrhea that is accompanied by fever or blood in the stool, or for diarrhea caused by pathogens other than E. coli.
- Hepatic Encephalopathy (HE): In adults with advanced liver disease, rifaximin is used to reduce the risk of overt HE recurrence. HE is a condition where the brain is affected by the liver's inability to remove toxins from the blood. It is often used in conjunction with lactulose and may be continued long-term. Studies have shown that rifaximin significantly reduces the risk of a breakthrough HE episode and related hospitalizations.
Off-Label Uses
Clinicians may also prescribe rifaximin for conditions not officially approved by the FDA, known as off-label use. The most common off-label use for rifaximin is for Small Intestinal Bacterial Overgrowth (SIBO). SIBO is a condition characterized by an excessive amount of bacteria in the small intestine, leading to symptoms like bloating, gas, and diarrhea. While not FDA-approved for this purpose, a 2017 meta-analysis found rifaximin to be safe and effective for treating SIBO.
Common Side Effects and Drug Interactions
Because rifaximin is poorly absorbed by the body, it is generally well-tolerated with a low incidence of side effects. However, some side effects can occur.
Common Side Effects:
- Nausea
- Headache
- Dizziness
- Fatigue
- Peripheral edema (swelling in the hands, ankles, or feet)
- Abdominal pain
Serious Side Effects:
- A severe and potentially life-threatening form of diarrhea called Clostridioides difficile-associated diarrhea (CDAD) can occur with antibiotic use. Patients should contact a doctor if diarrhea worsens or persists.
- Severe allergic reactions, including rash, hives, and swelling of the face, lips, or tongue.
Patients with severe liver impairment should use caution, as they may experience increased effects of the medicine.
Drug Interactions: Rifaximin can interact with a few other medications. It's particularly important to inform a healthcare provider if you are taking cyclosporine, warfarin, or certain other drugs, as the combination may increase the amount of rifaximin absorbed by the body or affect the efficacy of the other drug.
Rifaximin Comparison
Rifaximin is often considered for gastrointestinal conditions where gut bacteria play a role. Here is a comparison with another antibiotic sometimes used for similar purposes.
| Feature | Rifaximin | Neomycin |
|---|---|---|
| Primary Mechanism | Inhibits bacterial RNA synthesis. | Binds to bacterial ribosomes, inhibiting protein synthesis. |
| Absorption | Minimally absorbed (<0.4%). | Poorly absorbed, but more so than rifaximin. |
| Spectrum | Broad spectrum (Gram-positive and Gram-negative). | Primarily targets Gram-negative bacteria. |
| IBS-D Efficacy | Considered more effective than neomycin for IBS. In one study, 69% of patients had a clinical response, compared to 38% with neomycin. | Has been used for IBS, but studies suggest it is less effective than rifaximin. |
| Systemic Side Effects | Low risk due to minimal absorption. | Higher risk of systemic toxicity, including nephrotoxicity (kidney damage) and ototoxicity (hearing damage). |
Conclusion
Rifaximin is a unique, gut-selective antibiotic that offers a targeted treatment for several gastrointestinal and liver-related conditions. Its efficacy in treating IBS-D, traveler's diarrhea, and preventing HE recurrence is well-established, and its minimal systemic absorption contributes to a favorable safety profile. While it is an expensive medication with no generic currently available in the U.S., it serves as a valuable therapeutic option, particularly for patients who have not found relief with other treatments. As with any prescription medication, a discussion with a healthcare provider is essential to determine if rifaximin is the right choice for an individual's specific condition.
Authoritative Link: For more detailed prescribing information, consult the FDA label for Xifaxan..
