What Diagnosis Is Xifaxan Approved For?: A Comprehensive Medical Guide

October 14, 2025 •

3 min read

First approved by the FDA in 2004 for treating traveler's diarrhea, the antibiotic rifaximin, known by the brand name Xifaxan, has since received approval for two additional gastrointestinal diagnoses. A gut-selective antibiotic, what diagnosis is Xifaxan approved for now includes Irritable Bowel Syndrome with Diarrhea (IBS-D) and the reduction of recurrent overt hepatic encephalopathy (HE).

Quick Summary

Xifaxan (rifaximin) is an antibiotic approved to treat traveler's diarrhea caused by E. coli, irritable bowel syndrome with diarrhea (IBS-D) in adults, and to reduce the risk of recurring overt hepatic encephalopathy (HE).

Key Points

FDA Approval: Xifaxan is approved for traveler's diarrhea, irritable bowel syndrome with diarrhea (IBS-D), and the reduction of recurrent overt hepatic encephalopathy (HE).
Gut-Targeted Action: As a non-systemic antibiotic, rifaximin is minimally absorbed and primarily works locally in the gastrointestinal tract.
Specific Usage for Traveler's Diarrhea: For TD, Xifaxan is used for a specific course against noninvasive E. coli and is not suitable for bloody diarrhea or fever.
Retreatment for IBS-D: Adults with IBS-D receive a specific course, with options for retreatment if symptoms return.
Long-Term HE Management: For overt HE, Xifaxan is often used for long-term prevention of recurrence, usually with lactulose.
Side Effects and Risks: Common side effects are generally mild, but a risk of C. difficile colitis and hypersensitivity reactions exists, requiring careful monitoring.

Xifaxan, containing the active ingredient rifaximin, is an oral antibiotic primarily targeting bacteria in the digestive tract. Its non-systemic nature means very little of the drug is absorbed into the bloodstream, allowing it to treat intestinal issues with reduced systemic side effects. The FDA has approved Xifaxan for three specific conditions: traveler's diarrhea, irritable bowel syndrome with diarrhea (IBS-D), and reducing the recurrence of overt hepatic encephalopathy (HE). Each condition has its own recommended dosage and treatment duration.

Mechanism of Action: The Gut-Selective Approach

Rifaximin works mainly within the gastrointestinal tract by inhibiting bacterial RNA synthesis, thus reducing bacterial load. This localized action helps treat gut-related diseases without causing the widespread disruption of the gut microbiome often seen with other antibiotics. Because it's poorly absorbed, it's not effective for systemic infections and minimizes the risk of resistance outside the gut.

Approved Indications for Xifaxan

1. Traveler's Diarrhea

Xifaxan is approved for adults and children aged 12 and older to treat traveler's diarrhea caused by noninvasive E. coli. It is important to follow the prescribed treatment duration.

Important Considerations: It is not recommended for diarrhea with fever or blood, or for diarrhea caused by other pathogens.

2. Irritable Bowel Syndrome with Diarrhea (IBS-D)

For adults, Xifaxan is indicated for IBS-D, a condition involving abdominal pain, bloating, and diarrhea, often linked to gut bacteria imbalances. Treatment typically involves a specific course.

Retreatment: Adults with recurrent IBS-D symptoms can be retreated with the same course up to two additional times as directed by a healthcare professional.

3. Reduction of Recurrent Overt Hepatic Encephalopathy (HE)

HE is a serious complication of advanced liver disease where toxins like ammonia build up and affect brain function. Xifaxan is used to lower the chance of future HE episodes.

Treatment: For HE, Xifaxan is often used long-term, typically with lactulose, to manage the condition.

Comparison of Xifaxan Approved Uses

The table below summarizes the key differences in patient population and treatment approach for the three FDA-approved indications for Xifaxan:


Feature	Traveler's Diarrhea	Irritable Bowel Syndrome with Diarrhea (IBS-D)	Overt Hepatic Encephalopathy (HE) Recurrence
Patient Population	Adults and pediatric patients 12+	Adults	Adults
Treatment Approach	Short-term course for specific E. coli	Short-term course, potential for retreatment	Often long-term management
Duration	Typically 3 days	Typically 14 days	Long-term treatment
Retreatment	Not applicable	Up to 2 times for recurrence	Not applicable

Potential Off-Label Uses and Limitations

Xifaxan is sometimes used off-label for conditions like small intestinal bacterial overgrowth (SIBO), but this is not FDA-approved. Like other antibiotics, it carries a risk of Clostridium difficile colitis. For traveler's diarrhea, it's ineffective against some pathogens and should not be used for severe or bloody diarrhea. The FDA website is an authoritative source for approved uses and safety information.

Common Side Effects and Considerations

Due to its minimal absorption, Xifaxan is generally well-tolerated with few systemic side effects. However, some adverse effects can occur, varying slightly depending on the condition being treated.

Common side effects: Nausea, dizziness, fatigue, peripheral edema, and abdominal pain are among the reported side effects. Increased liver enzymes have been noted in IBS-D patients.
Potential for C. difficile: Xifaxan can lead to C. difficile-associated diarrhea (CDAD) by altering gut flora, allowing the bacterium to overgrow. Report persistent diarrhea to a doctor.
Hypersensitivity: Severe reactions like skin issues and angioedema are possible, requiring immediate discontinuation.

Conclusion

Xifaxan is a gut-specific antibiotic approved by the FDA for three key diagnoses: traveler's diarrhea caused by specific E. coli strains, irritable bowel syndrome with diarrhea (IBS-D) in adults, and reducing the recurrence of overt hepatic encephalopathy (HE). Its limited absorption makes it a targeted treatment with minimal systemic effects. Treatment duration varies by condition, from a short course for traveler's diarrhea to potentially long-term use for HE. Always consult a healthcare provider for proper diagnosis and guidance on using Xifaxan.

Disclaimer: This information is for general knowledge and should not be taken as medical advice. Consult with a healthcare professional before starting any new supplement or medication regimen.

Frequently Asked Questions

The primary function of Xifaxan (rifaximin) is to act as a gut-selective antibiotic, treating specific gastrointestinal conditions by targeting bacteria in the intestines with minimal absorption into the bloodstream.

No, Xifaxan is specifically approved for traveler's diarrhea caused by noninvasive strains of Escherichia coli. It is not effective for diarrhea with fever, blood in the stool, or caused by other pathogens like Campylobacter jejuni.

For Irritable Bowel Syndrome with Diarrhea (IBS-D) in adults, the treatment course for Xifaxan is typically 14 days. If symptoms recur, patients can be retreated up to two additional times as directed by a healthcare provider.

Whether Xifaxan is used long-term depends on the diagnosis. For overt hepatic encephalopathy, it is typically a long-term maintenance medication, whereas for traveler's diarrhea and IBS-D, it is used for a short course of treatment.

Common side effects include nausea, dizziness, fatigue, peripheral edema (swelling), and abdominal pain. The specific side effects can vary by the condition being treated.

Yes, Xifaxan can interact with other drugs. It's particularly important to inform your doctor if you are taking blood thinners like warfarin or other medications that inhibit P-glycoprotein, such as cyclosporine.

Xifaxan is not used for systemic (body-wide) infections because its minimal absorption into the bloodstream means it does not reach high enough concentrations outside the gut to be effective against those types of infections.