8 Xifaxan Side Effects and How to Manage Them

Xifaxan (rifaximin) is a prescription-only antibiotic that treats gastrointestinal (GI) symptoms caused by unwanted bacteria in your gut. This oral tablet isn’t filled at the pharmacy as often as some other antibiotics, but it's useful when called upon.

Xifaxan is 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 affect your risk of experiencing them.

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Xifaxan side effects at a glance

Xifaxan isn't absorbed into the bloodstream and generally causes very few side effects. This is especially true when Xifaxan is only taken for a short time — such as 3 days for traveler’s diarrhea or 14 days for IBS-D. 

But if you have HE, it’s typically recommended to take Xifaxan for a longer period to prevent recurrence. More side effects were reported in clinical trials when people with HE took Xifaxan for 6 or more months — versus when people took the medication for shorter periods for other conditions. 

Common Xifaxan side effects reported in clinical trials include:

• Swelling from fluid buildup

• Dizziness

• Fatigue

• Headache (when used to treat traveler’s diarrhea)

• Nausea (when used to treat IBS-D) 

• Stomach pain

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

• Itchiness

• Muscle spasms

• Joint pain

• Anemia

• Fever

• Depression

Rare but serious Xifaxan side effects include:

• Skin rashes

• C. diff-associated diarrhea

• Shortness of breath

• Facial swelling

• Severe muscle pain

Below, we’ll review how to manage eight of the most notable Xifaxan side effects. If you experience any bothersome side effects while taking Xifaxan — including the ones below and any others — let your healthcare provider know as soon as possible.

1. Swelling due to fluid buildup

If you’re taking Xifaxan for HE, the most likely side effect is swelling (edema) in your arms and legs. This is caused by fluid buildup. 

In some cases, Xifaxan can also cause swelling in the abdomen (belly). This type of swelling is called ascites. You may notice symptoms of weight gain, feeling full, or shortness of breath if this side effect occurs. Ascites is also very common in people with severe liver problems — the underlying cause of HE.

Reach out to your healthcare provider right away if you notice sudden or severe swelling in your limbs or abdomen. Swelling can cause additional problems, such as skin sores and infection, if left untreated. So your provider may prescribe you a medication to reduce the fluid buildup.

2. Dizziness

Dizziness is another common side effect of Xifaxan when taken for HE. If you feel lightheaded or unsteady, find a space to sit or lie down until you feel safe to move again. 

And there are a few tips to prevent falling if you occasionally feel dizzy:

• Drink plenty of fluids if you’re able to; dehydration can make dizziness worse.

• Move slowly and avoid sudden movements.

• Use a walking aid for balance and support.

Speak with your healthcare provider if your dizziness becomes frequent or bothersome. They can help you determine if your dizziness is related to taking Xifaxan or another issue, such as dehydration from diarrhea.

3. Fatigue

Fatigue (tiredness) is another relatively common side effect among people taking Xifaxan for HE. This may cause you to feel sleepier than usual or to have a lack of energy.

Thankfully, you can manage fatigue with relatively small lifestyle changes. For example, you can:

• 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 to improve your energy levels 

Contact your healthcare provider if your fatigue is severe or affecting your day-to-day life. They can help you manage your fatigue if it’s related to Xifaxan or pin down other possible causes. 

4. Headache

Some people taking Xifaxan for traveler’s diarrhea report experiencing headaches. These headaches tend to be short-lived, though.

If you experience mild headaches while taking Xifaxan, over-the-counter (OTC) pain relievers like acetaminophen (Tylenol) can offer relief. You can also try making some lifestyle changes, such as drinking more fluids, exercising, and getting a good night’s rest, for added support. And your pharmacist and healthcare provider can recommend other treatments that are safe for you to try.

If your headaches become severe or persistent — or are significantly affecting your daily life — it's a good idea to let your provider know. They can help you determine if the headaches are related to Xifaxan or if something more serious is going on.

5. Nausea

Nausea is another possible Xifaxan side effect. It’s been reported by some people taking Xifaxan for HE and for IBS-D. While the medication may be a contributing factor, both liver disease and IBS can cause nausea on their own.

You can take Xifaxan with a meal or snack to lessen your risk of feeling nauseous. And, in general, eating smaller meals can help improve an upset stomach. It’s also best to avoid trigger foods, such as greasy or spicy items, that might make your nausea worse.

If you’re having persistent nausea or stomach discomfort after taking Xifaxan, talk to your healthcare provider or pharmacist. They may recommend taking a prescription or OTC nausea medication to manage your nausea.

6. Rashes and itchiness

Some people taking Xifaxan report skin rashes and itchiness. If this happens to you, reach out to your healthcare provider. 

It’s important to talk to your healthcare provider even if your symptoms feel minor. Your body may be sensitive to Xifiaxan, and your provider may recommend that you take a different antibiotic. They can offer management tips to help address these side effects, too.

In some cases, these side effects indicate something more serious is going on. If you experience a sudden rash or severe itching while taking Xifaxan, you should seek medical care right away. These could be symptoms of a serious allergic reaction.

7. Muscle spasms

Some people taking Xifaxan report experiencing muscle spasms. But this may be related to dehydration or an electrolyte imbalance — and not necessarily the medication.

If you’re taking Xifaxan and start experiencing new or worsening muscle spasms, contact your healthcare provider. They can help you figure out what’s causing the issue. In some cases, they may want to order a lab test to check your electrolyte and hydration levels. Long-lasting or unmanaged electrolyte imbalances can potentially cause brain or heart issues. 

8. C. diff-associated diarrhea

It doesn’t happen often, but antibiotics, including Xifaxan, 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:

• Watery diarrhea

• Stomach cramps or pain

• Fever

• Fatigue

• Loss of appetite

Keep in mind, a C. diff infection can happen later on in treatment — even 2 months (or more) after finishing treatment with an antibiotic. Let your healthcare provider know right away if you experience any of the above symptoms after starting treatment with Xifaxan. C. diff infections can be life-threatening if they’re not promptly managed. If you have a confirmed C. diff infection, your provider will likely recommend that you stop taking Xifaxan and start taking a new antibiotic.

When to contact a healthcare provider about Xifaxan side effects

Although many people tolerate Xifaxan well, tolerability varies from person to person. Fortunately, most Xifaxan side effects are mild and can be managed with OTC medications and minor lifestyle changes.

But, like with all medications, serious side effects are possible. If you experience any unusual or concerning symptoms, it’s wise to contact your healthcare provider. Seek immediate medical care if you experience any of the following:

• Facial swelling

• Sudden fluid buildup

• A new rash

• Fever

• Trouble breathing

• Severe, watery diarrhea (or any diarrhea lasting more than 2 days)

Depending on the situation, your healthcare provider may need to treat your symptoms and change your antibiotic. However, don’t stop taking Xifaxan without talking to your provider — even if you feel better. Stopping treatment with Xifaxan too soon could make your infection worse and harder to treat.

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Written by:

Sheila McAdoo, PharmD

Sheila McAdoo, 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:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Reviewed by:

Daphne Berryhill, RPh

Daphne Berryhill, RPh, has two decades of experience as a clinical pharmacist. She spent most of her career in the Chicago area practicing in-home infusion.

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