7 Xifaxan Side Effects and How to Manage Them

Xifaxan (rifaximin) is a prescription-only antibiotic that treats diarrhea caused by unwanted bacteria in your gut. It’s FDA approved to treat three health conditions that stem from excess gut bacteria. It can treat traveler's diarrhea caused by Escherichia coli (E. coli), irritable bowel syndrome with diarrhea (IBS-D), and hepatic encephalopathy (HE). What’s more, Xifaxan is commonly taken “off-label” to ease the symptoms of a GI condition called small intestinal bacterial overgrowth (SIBO).

While Xifaxan is generally well-tolerated, it can cause some unwanted side effects. The reason you’re taking Xifaxan — and how long you’re taking it for — can make a difference in what side effects you experience. Here’s what you should know.

Xifaxan side effects at a glance

Xifaxan works in your gut and isn’t absorbed into the bloodstream. Side effects are more likely if you take Xifaxan continuously for HE. It generally causes very few side effects if you only take it for a short treatment course (3 or 14 days).

Common or mild Xifaxan side effects can include:

• Edema (swelling from fluid retention)

• Nausea

• Dizziness

• Fatigue

• Headache (when used for traveler’s diarrhea)

• Increased liver enzymes (when used to treat IBS-D)

• Muscle spasms

• Constipation (when used for HE)

Rare but serious Xifaxan side effects and risks include:

• Clostridioides difficile-associated diarrhea (C. diff diarrhea)

• Allergic reactions, including skin rashes and anaphylaxis

Let’s take a closer look at seven possible Xifaxan side effects and what to do if they occur.

1. Swelling due to excess fluid

If you’re taking Xifaxan for HE, you may experience edema (fluid-related swelling) as a side effect. This happens most often in your arms and legs. In some cases, Xifaxan can also cause swelling in the abdomen (belly). This type of swelling is called ascites.

Ascites and edema are also very common in people living with severe liver problems — the underlying cause of HE. So it’s hard to know for sure what role Xifaxan actually plays in the side effect.

For mild swelling, try elevating your legs or some movement-related exercise, such as walking or yoga. But reach out to your healthcare team right away if you notice sudden or severe swelling in your limbs or abdomen. They can help take steps to manage it before it becomes a bigger problem.

2. Nausea

Nausea is another possible Xifaxan side effect. The conditions Xifaxan treats can also cause nausea. So in many cases, it will improve as Xifaxan starts working.

In the meantime, try taking Xifaxan with a meal or snack to help reduce nausea. You can also try eating smaller, more frequent meals. And avoid greasy or spicy foods that can make nausea worse.

If you’re having persistent nausea or stomach discomfort after taking Xifaxan, talk to your healthcare team. They may recommend a prescription or over-the-counter (OTC) nausea medication to help.

3. Dizziness

Dizziness is another possible Xifaxan side effect. If you feel lightheaded or unsteady while taking it, find a space to sit or lie down until you feel safe to move again.

To help prevent dizziness while taking Xifaxan:

• Drink plenty of fluids, since dehydration can make dizziness worse.

• Move slowly and avoid sudden changes in position when sitting up or standing.

• Use a walking aid for balance and support if needed to help prevent falls.

Speak with your prescriber if dizziness is severe or doesn’t improve. They can help determine what’s causing it and the best next steps to take.

4. Fatigue

Fatigue (tiredness) is another relatively common side effect among people taking Xifaxan for HE. It’s also a common symptom of liver problems.

Small lifestyle changes may help you manage fatigue:

• Adjust your sleep schedule to allow for more quality sleep.

• Eat nutrient-rich foods for an energy boost.

• Stay hydrated to make sure your body is functioning well.

• Limit caffeine and alcohol to avoid an energy crash.

• Get regular physical activity and daily sunlight exposure if possible.

Contact your healthcare team if your fatigue is severe or affecting your day-to-day life. They can help pin down other possible causes and suggest treatment options.

5. Headache

Some people taking Xifaxan for traveler’s diarrhea reported headaches during clinical studies.

Most headaches are short-lived, and will go away on their own. You can also try resting or applying a cool compress. If needed, an OTC pain reliever may help. Just check with your healthcare team first to make you choose one that’s safe for you.

If your headaches become severe or persistent it's a good idea to let your prescriber know. This isn’t usual with Xifaxan, and could be a sign of something more serious going on.

6. Skin rash

You may experience a mild skin rash or itchiness while taking Xifaxan for HE. These symptoms are often related to liver problems. But Xifaxan can also cause serious allergic skin reactions in rare cases. So it’s best to talk to your healthcare team about any rashes that appear while taking Xifaxan. They can determine if it’s serious enough to stop the medication.

If you develop a skin rash along with blistering, trouble breathing, or swelling of your mouth and throat, seek emergency care right away. These can be signs of a serious allergic reaction.

7. C. diff-associated diarrhea

It doesn’t happen often, but Xifaxan and other antibiotics can contribute to a serious gut infection caused by a bacteria called C. diff. This infection occurs because antibiotics can change the normal balance of bacteria in the gut, which allows C. diff to overgrow.

A C. diff infection can cause symptoms such as:

• Severe watery diarrhea

• Stomach cramps or pain

• Fever

• Fatigue

• Loss of appetite

Keep in mind, a C. diff infection can happen at any time during Xifaxan treatment — even 2 months (or more) after you finish taking it. Seek medical care right away if you develop any of the signs and symptoms of C. diff diarrhea. This infection can be life-threatening if it isn’t managed properly.

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Written by:

Sheila Marie, PharmD

Sheila Marie, PharmD, is a licensed pharmacist in Virginia, New York, and the District of Columbia. She has worked in the pharmacy industry for 12 years and currently works as a community pharmacist.

Edited by:

Stacia Woodcock, PharmD

Stacia Woodcock, PharmD, is a pharmacy editor for GoodRx. She earned her Doctor of Pharmacy degree from the University of Kentucky and is licensed in New York and Massachusetts.

Reviewed by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

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