Rifaximin alternatives: what to try and when

Rifaximin is useful for several gut problems, but it’s not the only choice. Depending on why you’d use rifaximin — traveler’s diarrhea, hepatic encephalopathy (HE), small intestinal bacterial overgrowth (SIBO) or even C. difficile — other medicines or non-antibiotic options can be better. Below I’ll list common alternatives, what they do, and practical points to discuss with your clinician.

Common alternatives by condition

Traveler’s diarrhea: Azithromycin is a go-to in many places because it works well and is safe in pregnancy. Ciprofloxacin and other fluoroquinolones can work too, but resistance is rising and they have more serious side effects in some people. For mild cases, bismuth subsalicylate or loperamide can control symptoms without antibiotics.

Hepatic encephalopathy (HE): Lactulose is the non-antibiotic mainstay for preventing and treating HE. It lowers blood ammonia by changing gut bacteria and stool consistency. Neomycin and metronidazole are older antibiotic choices used when rifaximin isn’t an option, but they carry higher risks — think hearing problems (neomycin) or nervous system side effects (metronidazole).

SIBO and IBS‑D: Rifaximin is popular because it stays in the gut, but alternatives include metronidazole, ciprofloxacin, doxycycline or amoxicillin-clavulanate depending on the suspected bacteria. Non-drug approaches matter too — a low-FODMAP diet, targeted probiotics, and work with a dietitian often make a big difference alongside or instead of antibiotics.

C. difficile infection: Rifaximin is sometimes used in select cases, but the standard oral options are vancomycin or fidaxomicin. These are proven for C. difficile and usually preferred over rifaximin for initial treatment.

How to pick the right option

Choice depends on the condition, local resistance patterns, your allergies, kidney or liver function, pregnancy status, and prior antibiotic response. Side effects vary: lactulose commonly causes gas and loose stools; neomycin risks hearing or kidney damage with long use; fluoroquinolones can cause tendon or nerve problems in some people. Always weigh benefits against risks.

Ask your clinician these practical questions: What is the likely cause of my symptoms? Are there local resistance concerns? Can a non-antibiotic approach help first? What side effects should I watch for? If cost or access is an issue, ask about generics or alternative therapies.

Rifaximin alternatives are real and often effective, but they aren’t one-size-fits-all. Talk to a provider who knows your medical history and the specific condition. If you want, save this page and bring the points to your next visit — it helps make the conversation faster and clearer.