What antibiotics are similar to Xifaxan? A Guide to Alternatives

October 12, 2025 •

5 min read

Xifaxan (rifaximin) is a unique, poorly-absorbed antibiotic that acts primarily within the gut, minimizing systemic side effects. This targeted action is a major reason for its prescription, but when considering treatment options, many people ask, what antibiotics are similar to Xifaxan? The answer depends on the specific condition being treated.

Quick Summary

Different antibiotics and therapies, including neomycin, metronidazole, and ciprofloxacin, serve as alternatives to Xifaxan for conditions like SIBO and hepatic encephalopathy, each with distinct absorption profiles and side effects.

Key Points

Low Systemic Absorption: Xifaxan's primary benefit is its gut-specific action with minimal absorption into the bloodstream, which is not replicated by most other antibiotics.
Hepatic Encephalopathy Alternatives: Lactulose is a primary alternative, while neomycin is a less common choice due to its toxicity risk.
SIBO Treatment Options: Alternatives to Xifaxan for SIBO include neomycin (often in combination for methane-dominant cases), metronidazole, and herbal antimicrobials.
Traveler's Diarrhea Considerations: Ciprofloxacin is an alternative for traveler's diarrhea, but it has broader systemic effects and a greater risk of side effects compared to Xifaxan.
Recurrent C. difficile: Xifaxan may be an option for recurrent C. difficile infection in patients who have failed metronidazole treatment, as increasing resistance to metronidazole has been noted.
Personalized Treatment: The best antibiotic choice depends on the specific condition, type of bacteria, and individual patient factors; consultation with a healthcare provider is essential.

Understanding Xifaxan's Unique Profile

Xifaxan, the brand name for rifaximin, is a rifamycin antibiotic. Its distinguishing feature is its poor systemic absorption, meaning it stays primarily in the gastrointestinal tract and has minimal effects elsewhere in the body. This makes it an ideal treatment for gut-related issues where bacterial overgrowth is the problem, such as small intestinal bacterial overgrowth (SIBO), irritable bowel syndrome with diarrhea (IBS-D), and hepatic encephalopathy (HE).

When searching for similar medications, it is crucial to consider the specific condition being addressed. While other antibiotics can target intestinal bacteria, they often differ significantly from Xifaxan in their mechanism, systemic absorption, and potential side effects. The high cost of Xifaxan and the risk of resistance over time are other common reasons patients may seek alternatives.

Alternatives for Hepatic Encephalopathy (HE)

Hepatic encephalopathy is a neurological complication of liver disease, partly caused by ammonia produced by gut bacteria. The goal of treatment is to reduce these ammonia-producing bacteria. For decades, the standard of care involved non-absorbable options.

Lactulose: This non-absorbable sugar is a long-standing first-line treatment for HE. It works by causing bowel movements, which helps flush out toxins like ammonia. It also draws water into the colon and acidifies the gut environment, converting ammonia into a non-absorbable form. Lactulose is effective and much less expensive than Xifaxan, but it can cause significant side effects like diarrhea, bloating, and flatulence.
Neomycin: As a non-absorbable antibiotic, neomycin was historically used for HE. Studies comparing neomycin and Xifaxan found similar efficacy in improving HE symptoms. However, long-term use of neomycin is limited by significant risks of toxicity, including kidney and hearing damage, which are not concerns with Xifaxan's minimal absorption.

Alternatives for Small Intestinal Bacterial Overgrowth (SIBO)

SIBO involves an abnormal increase in bacteria in the small intestine. While Xifaxan is the most-studied antibiotic for SIBO, several alternatives and combination therapies are used, especially in cases of specific bacterial dominance or treatment failure.

Metronidazole (Flagyl): An antibiotic sometimes used for SIBO. Studies have compared metronidazole and Xifaxan for SIBO, suggesting Xifaxan may have a higher eradication rate and be better tolerated. Metronidazole also carries a risk of side effects like a metallic taste and nausea and can cause peripheral neuropathy with long-term use.
Neomycin: When methane-producing bacteria are dominant in SIBO, a combination of Xifaxan and neomycin may be more effective than Xifaxan alone. This combination is used with caution due to the risks associated with neomycin, but the short-term course can be highly effective.
Other Antibiotics: Ciprofloxacin and amoxicillin-clavulanate are less common but potential alternatives, particularly if other options are not viable. However, their broader systemic absorption means a higher risk of side effects and disruption of the broader gut flora.
Herbal Antimicrobials: Some studies show herbal therapies like oregano oil, berberine, and allicin (from garlic) can effectively reduce SIBO symptoms, with potentially fewer side effects than prescription antibiotics.

Alternatives for Traveler's Diarrhea

Caused by E. coli, traveler's diarrhea is a key indication for Xifaxan. When an alternative is needed, a doctor may consider other options based on the specific bacteria involved.

Ciprofloxacin (Cipro): A fluoroquinolone antibiotic used for various infections, including infectious diarrhea. Ciprofloxacin is an option for traveler's diarrhea but has significantly more systemic absorption and carries more serious potential side effects, such as tendon rupture and nerve damage, compared to Xifaxan.
Over-the-Counter Options: Medications like loperamide (Imodium A-D) or bismuth subsalicylate (Kaopectate) can help manage the symptoms of diarrhea but do not treat the underlying bacterial infection like antibiotics.

Comparison of Xifaxan and Key Alternatives


Feature	Xifaxan (Rifaximin)	Neomycin	Metronidazole (Flagyl)	Ciprofloxacin (Cipro)
Absorption	Poor systemic absorption; acts locally in the gut	Minimal systemic absorption	Good systemic absorption	Good systemic absorption
Drug Class	Rifamycin antibiotic	Aminoglycoside antibiotic	Nitroimidazole antibiotic	Fluoroquinolone antibiotic
Key Conditions	SIBO, IBS-D, HE, Traveler's Diarrhea	HE, Methane-predominant SIBO	SIBO, C. difficile (historically)	Traveler's Diarrhea, various infections
Common Side Effects	Peripheral edema, nausea, dizziness	Nausea, diarrhea, kidney/ear toxicity (long-term)	Nausea, metallic taste, diarrhea	Nausea, diarrhea, tendon issues
Mechanism	Inhibits bacterial RNA synthesis within the gut	Interferes with bacterial protein synthesis	Damages bacterial DNA	Inhibits bacterial DNA enzymes
Resistance	Potential for resistance over time	Can develop resistance	Increasing resistance in C. difficile	Growing resistance concerns

Navigating Prescribing Decisions

For many gastrointestinal conditions, the choice of antibiotic involves balancing efficacy, safety, and cost. Xifaxan’s unique gut-specific action and excellent safety profile make it a first-line choice for many conditions. However, in specific cases, alternatives like neomycin, metronidazole, or ciprofloxacin, or even non-antibiotic treatments, may be considered.

For Hepatic Encephalopathy: Lactulose is often the initial therapy, with Xifaxan reserved for maintenance or when patients do not respond well to lactulose. Neomycin is now considered a second-line option due to its greater toxicity risk, especially for long-term use.
For SIBO: Xifaxan is the preferred antibiotic, especially for hydrogen-dominant SIBO. For methane-dominant SIBO, combining Xifaxan with neomycin is a common strategy. For patients who fail these treatments or have contraindications, herbal antimicrobials are a growing area of interest.
For Traveler's Diarrhea: While ciprofloxacin is an option, Xifaxan is often preferred for its localized action and milder side effect profile. The choice depends on the specific pathogen and individual risk factors.

Conclusion

While no antibiotic is an exact copy of Xifaxan, several alternatives exist, each with its own specific uses and considerations. Xifaxan's unique low systemic absorption minimizes side effects and limits its impact on the wider microbiome. When considering alternatives like neomycin, metronidazole, or ciprofloxacin, it's essential to weigh the risk of systemic side effects against the potential benefits for the targeted condition. Patients should always consult a healthcare provider to determine the most appropriate and safest treatment plan. For detailed prescribing information, resources like the FDA website can provide further guidance on approved uses and safety data.

List of Potential Alternatives and Their Primary Use

Neomycin: Combination therapy for methane-predominant SIBO and second-line for HE.
Metronidazole (Flagyl): Used for SIBO, though with potential for higher failure rates than Xifaxan; historically used for C. difficile.
Ciprofloxacin (Cipro): An option for traveler's diarrhea and other systemic infections.
Lactulose: A non-antibiotic first-line option for HE.
Herbal Antimicrobials: Can be an alternative for SIBO management.
Oral Vancomycin: An alternative for C. difficile infection.

Frequently Asked Questions

The key difference is Xifaxan's poor absorption, which means it works locally in the gut with minimal systemic effects. This results in fewer side effects and less impact on the body's overall microbial balance compared to other antibiotics that are absorbed systemically.

Neomycin is sometimes used for SIBO, particularly in combination with Xifaxan for cases of methane-dominant SIBO. However, long-term use of neomycin is limited by potential ototoxicity and nephrotoxicity, unlike Xifaxan.

Metronidazole is not a direct substitute for Xifaxan for traveler's diarrhea, though it has been used for other types of infectious diarrhea. Metronidazole has more systemic absorption and different side effects than Xifaxan, and resistance is a concern in some infections like C. difficile.

Lactulose and Xifaxan are both effective for HE, but they work differently. Lactulose promotes bowel movements and traps ammonia, while Xifaxan directly reduces ammonia-producing bacteria. Lactulose is less expensive but has a higher incidence of uncomfortable gastrointestinal side effects like diarrhea and bloating.

Yes, some studies show that herbal antimicrobial therapies, such as those using oregano oil, berberine, or allicin, can be effective in managing SIBO symptoms. An elemental diet, which starves gut bacteria, is another non-antibiotic option.

In cases of recurrent C. difficile that do not respond to metronidazole, Xifaxan has shown promise. Other options include vancomycin or fidaxomicin, depending on the severity of the infection.

Yes, Xifaxan can be very expensive, and some alternatives may be less costly. However, the cost often depends on the condition being treated and the specific alternative. For example, lactulose is much cheaper for HE, and some generic antibiotics are cheaper for SIBO, but they may not have the same safety profile or efficacy.