When Xifaxan Isn't Available, What Are Your Options?

Xifaxan (Rifaximin) is one of those medications that's hard to replace. It works locally in the gut, has relatively few systemic side effects, and it's FDA-approved for conditions that don't have many treatment options. So when you can't fill your prescription — whether because of availability issues, insurance denials, or the $1,600 to $2,200 price tag — it's understandable to feel stuck.

But you do have options. Let's walk through what Xifaxan does, how it works, and which alternatives your doctor might consider depending on your condition.

What Is Xifaxan and How Does It Work?

Xifaxan is a non-absorbable rifamycin antibiotic. Its generic name is Rifaximin, and it's made by Salix Pharmaceuticals (a Bausch Health company).

Here's what makes it unique: unlike most antibiotics that get absorbed into your bloodstream and travel throughout your body, Rifaximin stays almost entirely in your gastrointestinal tract. Less than 0.4% of the drug is absorbed systemically. It works by binding to bacterial RNA polymerase, which stops bacteria from making the proteins they need to survive.

This gut-targeted action makes Xifaxan effective for:

• Hepatic encephalopathy (HE): Reduces ammonia-producing bacteria in the gut, lowering the risk of HE recurrence
• IBS-D: Targets gut bacteria involved in diarrhea-predominant irritable bowel syndrome
• Travelers' diarrhea: Fights E. coli infection in the gut
• SIBO (off-label): Treats small intestinal bacterial overgrowth

Alternatives by Condition

Because Xifaxan treats several different conditions, the right alternative depends on why you're taking it. Always talk to your doctor before switching medications.

For Hepatic Encephalopathy: Lactulose

Lactulose is the most widely used alternative — and it's actually the first-line treatment for hepatic encephalopathy. It's an osmotic laxative that works by pulling water into the colon and lowering the pH of stool, which reduces the amount of ammonia your gut bacteria produce and helps your body eliminate it faster.

Key facts about Lactulose:

• Available as a generic — costs $15 to $60 per month
• Taken as an oral solution, typically 2 to 3 times daily
• Very widely available at virtually every pharmacy
• Often used together with Xifaxan, not just as a replacement
• Main side effects: bloating, gas, diarrhea, and abdominal cramping

If you're currently on both Lactulose and Xifaxan and can't get Xifaxan, continuing Lactulose alone is the standard backup approach. Your doctor may adjust the dose.

For Hepatic Encephalopathy: Neomycin

Neomycin is an older aminoglycoside antibiotic that, like Xifaxan, reduces ammonia-producing bacteria in the gut. It was used for hepatic encephalopathy long before Xifaxan came along.

Key facts about Neomycin:

• Available as a generic — relatively inexpensive
• Taken orally, typically 500 mg to 1,000 mg every 6 to 8 hours
• Effective but has more serious side effects than Xifaxan, including potential kidney damage (nephrotoxicity) and hearing loss (ototoxicity) with long-term use
• Generally used short-term or when other options aren't available

Neomycin is not a first choice for most doctors, but it remains an option when Xifaxan and Lactulose aren't sufficient or available.

For IBS-D: Eluxadoline (Viberzi)

Eluxadoline, sold under the brand name Viberzi, works completely differently from Xifaxan. Instead of targeting gut bacteria, it acts on opioid receptors in the gut to slow down intestinal motility and reduce diarrhea.

Key facts about Viberzi:

• FDA-approved specifically for IBS-D in adults
• Taken as 75 mg or 100 mg tablets twice daily with food
• It's a Schedule IV controlled substance
• Cannot be used in patients without a gallbladder (risk of sphincter of Oddi spasm and pancreatitis)
• Cash price ranges from $1,400 to $1,800 per month

Viberzi addresses the symptoms of IBS-D (diarrhea, urgency) rather than the bacterial component. It may be appropriate if Xifaxan didn't work well for you or isn't available.

For IBS-D: Alosetron (Lotronsa)

Alosetron is a 5-HT3 receptor antagonist approved for severe IBS-D in women who haven't responded to other treatments. It slows gut motility and reduces pain signaling from the gut.

Key facts about Alosetron:

• Only approved for women with severe IBS-D
• Available through a restricted prescribing program due to risk of serious GI side effects (ischemic colitis, severe constipation)
• Dose starts low — 0.5 mg twice daily, may increase to 1 mg twice daily
• Available as a generic, making it more affordable than Xifaxan

Alosetron is a last-resort option for most patients, but for those with severe symptoms who can't access Xifaxan, it's worth discussing with your gastroenterologist.

For SIBO: Other Antibiotic Options

Xifaxan is the most commonly prescribed antibiotic for small intestinal bacterial overgrowth (SIBO), even though this is an off-label use. If you can't get Xifaxan for SIBO, your doctor may consider:

• Metronidazole (Flagyl): A widely available generic antibiotic, though it has more systemic side effects
• Ciprofloxacin: Sometimes used for SIBO, but fluoroquinolone side effects make it a less preferred choice
• Amoxicillin-clavulanate: May be used in combination regimens for SIBO

These alternatives are all available as generics and cost significantly less than Xifaxan, but they also have more side effects because they're absorbed systemically.

A Quick Comparison

Here's how the main alternatives stack up:

• Lactulose — Best for HE, very affordable ($15–$60/month), widely available, first-line treatment
• Neomycin — HE alternative, inexpensive, but more side effects with long-term use
• Viberzi (Eluxadoline) — IBS-D, similar price to Xifaxan, controlled substance, not for patients without gallbladder
• Alosetron (Lotronsa) — Severe IBS-D in women only, restricted program, generic available

Final Thoughts

Xifaxan is a unique medication, and no alternative is a perfect one-to-one replacement. But depending on your condition, there are real options that your doctor can prescribe — many of which are more affordable and easier to find.

If your main challenge is finding Xifaxan rather than affording it, try Medfinder to search pharmacy stock in your area. And if cost is the issue, our guide on saving money on Xifaxan may help you access the medication at a price you can manage.

Always talk to your doctor before making any changes to your medication.