Help Navigating Alternative Drug Options for Xifaxan

Hello and thanks for your question!

We’ve had a number of people reach out asking about Xifaxan alternatives, and we imagine many of these questions are coming from people with Medicaid, where Xifaxan is no longer being covered.

The goal here isn’t to dive into why Xifaxan is no longer covered by many Medicaid plans. That change is tied to the manufacturer leaving the Medicaid Drug Rebate Program (MDRP) and the 340B Drug Pricing Program (340B). You can read the manufacturer’s explanation on their website. I'll focus on discussing alternative options like you asked for.

That said, it’s worth noting that even if you have Medicaid, you may still be eligible for financial assistance through a manufacturer patient assistance program (in fact, there is a Medicaid specific application form - bh-pap-application-pap-medicaid.pdf).

Xifaxan Alternatives

Xifaxan has several different uses, and the most appropriate alternatives depend on what you are taking the medication for.

Xifaxan has three FDA-approved indications:

• Hepatic encephalopathy
• Irritable bowel syndrome with diarrhea (IBS-D)
• Traveler’s diarrhea

In addition, Xifaxan is commonly used off-label for the treatment of small intestinal bacterial overgrowth (SIBO), so I'll cover that too.

Below, I walk through each approved use of the drug (and SIBO) and discuss alternative treatment options for each.

Hepatic Encephalopathy

Hepatic encephalopathy happens when the liver can no longer clear toxins from the blood, especially ammonia. When these toxins build up, they can affect thinking, alertness, memory, and behavior.

Xifaxan works by reducing the gut bacteria that produce ammonia and other toxins.

Where Xifaxan fits in treatment

While lactulose is often the first medication started, Xifaxan is widely considered the preferred option for long-term prevention of hepatic encephalopathy. Many patients stay on Xifaxan continuously once it is started.

Compared with relying on lactulose alone, Xifaxan is often:

• Easier to take consistently over the long term
• Better tolerated day to day
• Less likely to cause diarrhea, bloating, or cramping
• Associated with fewer repeat hospitalizations

Because of this, Xifaxan is commonly used as a preferred medication for long-term management, either on its own or alongside lactulose. Losing coverage for Xifaxan can be especially difficult for people using it to manage this condition.

What the alternatives look like

• Lactulose is the main alternative and can work well, but it can be difficult to tolerate and harder to take consistently long term.
• Other antibiotics exist, but they are generally less favored for long-term use.

For hepatic encephalopathy, Xifaxan is not a short-term medication. It is often used continuously to help prevent future episodes, which is why loss of coverage can be especially challenging. If you are using Xifaxan for HE, I highly recommend trying to utilize the patient assistance program for the drug.

Irritable Bowel Syndrome With Diarrhea (IBS-D)

IBS with diarrhea is a chronic condition that can cause abdominal pain, bloating, urgency, and loose stools. Symptoms often fluctuate and may be triggered by food, stress, or gut sensitivity.

Xifaxan is thought to work by changing the balance of gut bacteria that may be contributing to symptoms like bloating and diarrhea.

Where Xifaxan fits in treatment

Xifaxan is an FDA-approved treatment for IBS-D, but it is usually not the first step. It is often used when diet changes and symptom-based treatments have not provided enough relief.

Unlike many IBS medications, Xifaxan is taken as a short course, not as a daily long-term medication.

What the alternatives look like

• Diet changes, including identifying trigger foods or trying a low-FODMAP approach, are often the starting point.
• Loperamide can help slow diarrhea, though it may not help as much with pain or bloating.
• Bile acid binders can help some people when diarrhea does not respond to loperamide.
• Medications for pain and cramping, such as antispasmodics or low-dose antidepressants, are often used alongside gut-focused treatments.

Traveler’s Diarrhea

Traveler’s diarrhea is common when visiting areas with different food and water safety standards. Most cases are mild and improve on their own within a few days.

Where Xifaxan fits in treatment

Xifaxan may be used in certain cases of traveler’s diarrhea, mainly when symptoms are more than mild and there is no fever or blood in the stool. It works best for infections caused by non-invasive bacteria.

What the alternatives look like

• Fluids and electrolytes are the most important treatment and are often all that is needed.
• Loperamide can help reduce stool frequency in mild to moderate cases.
• Azithromycin is usually preferred when symptoms are severe or when fever or bloody stools are present.

Xifaxan is a situational option for traveler’s diarrhea. It can be helpful in specific cases but is not used for every type of infection.

Small Intestinal Bacterial Overgrowth (SIBO)

SIBO occurs when too many bacteria grow in the small intestine, leading to symptoms like bloating, gas, abdominal discomfort, diarrhea, or constipation.

Where Xifaxan fits in treatment

For many patients, Xifaxan is considered a first-choice treatment once SIBO is confirmed. It stays in the gut and is generally well tolerated.

Some types of bacterial overgrowth may require Xifaxan alone, while others may need combination treatment. As with hepatic encephalopathy, losing coverage for Xifaxan can create a difficult situation, since it is a first-line option for SIBO.

What the alternatives look like

• Other antibiotics can be used and may work well for some people, though side effects and tolerability vary.
• Addressing underlying causes, such as slow gut movement or medication effects, can help reduce recurrence.
• Diet changes may help symptoms but usually do not replace antibiotics when SIBO is confirmed.

Final Thoughts

I hope this answer helped clarify where Xifaxan fits in and what alternatives may be available.

I also recommend reviewing the manufacturer’s website for patient assistance options. While many people with Medicaid are not eligible for patient assistance programs, there may be exceptions in this situation.

As always, be sure to speak with your doctor about your options.