What you need to know about taking Xifaxan (Rifaximin) to treat your SIBO

If you’ve been prescribed Xifaxan® (Rifaximin) for small intestinal bacterial overgrowth (SIBO) then you aren’t alone. It’s quickly becoming the most commonly used treatment by doctors around the world. However, it’s still an antibiotic and it can be scary to think about putting it in your body.

If you are debating taking it then this article is for you.

I was petrified to take it. It took me weeks to get the courage up to ask my primary care physician to prescribe it. Then I filled the prescription and it sat on my counter for another week while I continued to research it.

In the end I took it and it made a big impact on my symptoms. So let me start by saying whether you take it or not I hope that this article at least helps you make the right decision for your body.

In this article, I’m going to cover:

  1.     What Xifaxan® (rifaximin) is
  2.     How and where it works
  3.     Side effects to be aware of, including C.difficile and resistance
  4.     Efficacy in treating SIBO
  5.     What to do if it doesn’t work

What is Xifaxan®(Rifaximin)?

Xifaxan® (Salix Pharmaceuticals) is the brand name for rifaximin (the generic form).

Rifaximin was introduced in Italy in 1987 and was developed specifically to treat traveler’s diarrhea.However, as you now know it’s most commonly used to treat SIBO infections.  

According to the authors of a review on SIBO and IBS, they stated that “rifaximin is the best treatment for SIBO among patients with IBS.”2

Throughout this article, I will refer to rifaximin since the majority of researchers use this form in their studies. Rifaximin is a broad-spectrum antibiotic, meaning that it kills different types of bacteria (gram-positive and negative bacteria, including aerobes and anaerobes).

Rifaximin is considered a non-absorbable antibiotic-it acts mainly in the gastrointestinal (GI) tract and very little of it, a scant 0.01%, is found in the bloodstream.3 This is a very strong positive for rifaximin compared to other antibiotics.

Just to give you some perspective, according to the monograph on penicillin V (a class of penicillin antibiotic), 25-73% of it is absorbed from the gastrointestinal tract into the systemic circulation, meaning that it affects the whole body system.

As you can start to see, rifaximin is not your typical antibiotic. In fact, there’s nothing else quite like it. It’s interesting properties of not being absorbed is what makes it so helpful in treating infections directly involving the GI tract, like IBS and SIBO, with less risks of side effects.

How Rifaximin Works in the Body

Rifaximin is so good at treating SIBO because it does its job in the small intestine and nowhere else. That is why it is becoming so popular in treating SIBO. But besides killing bacteria, rifaximin also does some other pretty cool things:  

  1.    A study in rats found that it reduces inflammation in the small intestine and decreases sensitivity to pain.4
  2.    It increases the beneficial bacteria in the colon while keeping the overall bacterial community stable in the colon.3
  3.    When small intestinal cells were treated with rifaximin, it prevented bad bacteria from attaching to them.5

The fact that it increases beneficial bacteria is pretty astounding because most antibiotics have a very negative impact on the bacteria in the gut.6

Which means that when you take rifaximin to treat your SIBO, you might start feeling better not only because it’s reducing the overgrowth in your small intestine, but it’s also fighting inflammation, preventing bad bacteria from sticking around and keeping your good  bacteria in your colon happy.

But I’ve Heard that Antibiotics Have Bad Side Effects

For some people, it’s antibiotics that might have put you in this position of battling SIBO to begin with. Now you are being told by your doctor to turn around and take an antibiotic to treat it. That doesn’t sound right!

When penicillin was introduced in the 1940’s, it revolutionized how medicine was practiced. Antibiotics are powerful drugs that can save lives; however, they also carry risks. Side effects of antibiotics can be mild to life threatening. It can be scary when you are the one who is faced with the need to take an antibiotic.

Different antibiotics have been used to treat SIBO, such as fluoroquinolones, metronidazole, tetracycline, amoxicillin-clavulanic acid, chloramphenicol, etc.; however, many are associated with adverse events, some of them severe.7 In fact, out of 142,505 visits to the ER that occurred in 2004-2006,19.3% of them were associated with systemic antibiotics.

Most of the adverse events from taking antibiotics relate to the fact that they impact the entire body, in other words, they become systemic. This isn’t the case with rifaximin because it specifically targets the small intestine.

In addition, all other antibiotics that have been studied reduce the abundance of bacteria in the intestinal tract by 30% and sometimes, the microbial community may not totally recover. Alterations in the bacteria can last for months to years.

OK, Then What are the Side Effects of Rifaximin?

Just as a reminder, only a tiny bit (<0.01%) of rifaximin is found in the bloodstream. 

Because it’s not absorbed, it poses minimum risk of toxicity.3

Researchers pooled together 17 studies representing 815 patients with SIBO who were being treated with rifaximin. Reported adverse events was 4.6% overall-that is pretty low compared to systemic antibiotics.7 Of those 17 studies, I looked up the study that was shown to have the highest adverse events (14/80 participants-17.5%) just to see what the actual symptoms were.9 Indigestion and constipation were the two most frequently reported adverse events. No ER visits or hospitalizations were reported. That’s promising! Another study looked at the safety profile of rifaximin long term (>24 months). The dosage was 550 mg twice per day to treat people with chronic liver problems. The authors found that the patients treated with rifaximin long term had decreased hospital admissions without an increase in adverse events or any change in survival outcomes.10

For SIBO patients, the typical dosage of rifaximin is 550 mg 3 times per day for 2 weeks, which is way less than what’s been safely studied.

I’ve worked with a lot of SIBO patients who were on rifaximin and most tolerate it well, including myself. The main issues that have been reported by my patients have been an increase in GI symptoms and fatigue. This could be due to the herxheimer reaction, which is a short-term detoxification reaction associated with large numbers of microorganisms dying at once.

One of my patients reported an increase in heart rate within a few hours of taking rifaximin and in that situation, it was recommended that she stop taking it. For a more complete list of side effects, please refer to this site: https://www.rxlist.com/xifaxan-side-effects-drug-center.htm

We are all different in how we respond to pharmaceutical and natural treatments, so be  sure and be in communication with your prescribing physician while taking rifaximin.

What Worried Me the Most about Taking Rifaximin

When I took this drug to treat my SIBO, what worried me the most was the risk of developing a really dreadful condition called Clostridium difficile infection (CDI). You may not have heard about this infection, but I saw a lot of it while working in the hospital setting and it was pretty scary. C. difficile is a bacterium that colonizes in the colon and can produce harmful toxins, leading to colitis (inflammation of the colon). It can be difficult to eradicate and can become resistant to the usual treatment. It is most commonly associated with systemic antibiotic use, because antibiotics kill the good bacteria in the colon that would normally keep this bacteria in check.

Do People Who Take Rifaximin Get CDI?

Researchers reviewed 211 patient charts who had a chronic liver condition and had been treated with rifaximin. On average, they were treated for 250 days at doses ranging from 800 mg – 1600 mg per day. No one developed CDI during the treatment period.11

However, in one study, CDI was reported to occur in one patient (out of 67) after they had finished taking 1200 mg of rifaximin for 4 weeks to treat SIBO.12 The authors failed to mention how much time had elapsed from the start of the infection to when the participant had stopped the rifaximin, as well as any risk factors associated with developing this infection. Nevertheless, there have been other accounts of a few patients with liver disease and Crohn’s disease developing this infection while being treated with rifaximin.

Keep in mind, these rates are considered low, but it can’t be said that the risk of CDI is 0% with rifaximin.13

On the other hand, there is research to indicate that rifaximin is actually effective for the treatment of C. difficile as well as helping prevent recurrence.1

So what does that mean for us? Well, I’m sorry that I can’t say that there are no risks of getting CDI when taking rifaximin to treat your SIBO. But studies show that the risk is low compared to the systemic antibiotics, so that is a positive. And again, it is used to actually treat the infection.

My advice to you is that if you are really worried about this or you have had a previous infection with C. difficile, please consult with your prescribing physician to determine your specific risks vs. benefits of taking it. It is always better to go into a treatment with your eyes wide open!

Antibiotics and Bacterial Resistance

This concept of bacterial resistance may be new to you, but according to the Centers for Disease Control and Prevention (CDC), bacteria resistance to antibiotics is a serious public health problem throughout the world. 

Bacterial resistance happens when antibiotics are overused, misused and are so widespread, that the bacteria that the antibiotic is trying to kill have adapted to it. Therefore, it stops being as effective. The CDC reports that each year at least 2 million Americans are infected with these drug resistant strains of bacteria and thousands die from them.14

Is there a possibility that my SIBO bacteria will become resistant to rifaximin? 

The development of resistant strains doesn’t seem to happen with rifaximin,15 even after being treated for 12 weeks.16 Although some researchers caution that more studies need to be conducted to determine if resistance develops over the long term.17

What this means for us is that we should take rifaximin with care and do everything that we can to enhance its effectiveness while we are taking it. See the section “What should I do if rifaximin doesn’t work?”

How Well Does Rifaximin Work as a SIBO Treatment?

Maybe after reading this, you aren’t so afraid of taking rifaximin. The more educated I became about rifaximin, the less worried I was about taking it.

But you may be wondering, how well does it work? Researchers analyzed 36 studies including 1331 participants and reported that the eradication rates of rifaximin for SIBO was approximately 71-73%. The higher the dosage, the better the results were.

The same researchers reviewed ten studies that measured symptoms before and after treatment with rifaximin. Approximately 68% of participants whose SIBO was eradicated reported overall improvement or were completely symptom free after treatment.

You can see that rifaximin is pretty effective in treating SIBO. It worked for me, but it doesn’t work for everyone.

My Experience Taking Rifaximin

I made the decision to take rifaximin because I needed something stronger than the herbs that I had been taking to treat my SIBO. I was still searching for my underlying causes and needed some symptom relief! At the time that I went on rifaximin, I could barely breathe because my bloating was so bad. My digestive system had completely stopped working.

Within a few days of treatment, I could breathe again and things started moving along. On the other hand, I have had patients who saw only mild symptom improvement or didn’t have any symptom improvement. They tell me “I felt nothing, good or bad.”

We all differ, but it is nice to know that there are other options (see the section “the biggest problem with rifaximin).”

What to do if Rifaximin Doesn’t Work

It can be very disappointing to finally make the decision to take rifaximin to help with your  SIBO and then, major let down-it didn’t work for you, or you didn’t get the results that you expected.

Here are some reasons why rifaximin may not work:

  • If the hydrogen and/or methane levels from the breath test were really high, then one round may not cut it and several rounds may be warranted. Unfortunately, insurance varies on how many rounds are covered and the allowable timing between rounds. However, specific herbs can be used after you’ve stopped taking it to help reduce levels.
  • If your SIBO is from predominantly methane producing microorganisms, then another drug such as neomycin will need to be taken at the same time.
  • Other infections may be involved, like small intestinal fungal overgrowth (SIFO) or parasites.
  • Improperly functioning digestive system-this is a big, big category and many factors need to be addressed to set the stage for a healthy digestive tract. For example, researchers have learned that the presence of bile acids greatly increases (100 fold!) the ability of rifaximin to dissolve.3 For those of us without gallbladders-yes, me included, we may need extra digestive support to get maximum effectiveness when taking rifaximin

There are many variables that affect how someone will respond to rifaximin. In addition, taking rifaximin concurrently with prebiotics can increase its effectiveness.18 Finding out what you need to do to increase its effectiveness will give you a better response rate.

Also remember that based on the studies above, you have an approximately 70% chance of killing SIBO.

The Biggest Problem with Rifaximin

A big con of Xifaxan® is that it is very expensive. Patients have called me after visiting the pharmacy to pick up their prescription with sticker shock. Some were being told that they owed  $2,000! At the time of writing this post, the generic form, rifaximin, is not available in the US. At thousands of dollars out of pocket, Xifaxan® is just not cost effective unless your insurance covers it.

Xifaxan® was approved by the FDA to treat IBS with diarrhea in 2015, which has helped patients get better insurance coverage. If your insurance denies coverage and you are unable to afford Xifaxan®, don’t despair, there are other treatment options available!

As You Make Your Treatment Choice…

Just remember, rifaximin isn’t a magic bullet! In my experience, you can’t just take it and expect symptoms to just melt away and never come back, without addressing many other factors.

Since this article is about the safety of rifaximin, I didn’t mention the relapse rate, but it can be high. This is common for SIBO, whatever treatment you are using. Once you finish taking the rifaximin, you’re not done. You will need to take the necessary steps to prevent relapse. These steps will depend upon your underlying cause.

My approach will typically include motility agents and lifestyle factors to enhance motility, finding the right diet for you to control symptoms and addressing the underlying cause(s) individual to your case.

Even after reading this post and talking to your doctor, you still may not feel comfortable about taking rifaximin, and that is fine. There are other options to help with your SIBO.

These include herbal antimicrobials and the elemental diet. And if it makes you feel better, I’ve tried them all!

If you have been prescribed rifaximin for your SIBO and you need help developing a comprehensive approach to make the most out of taking it, then please schedule a free, 30 minute SIBO Troubleshooting Consultation.


Disclaimer: There are always risks when taking drugs or even natural treatment options. You will need to weigh the pros and cons of any treatment and make that decision with your prescribing physician.

PSS. Another thing, as a professor, I try to give the most unbiased account that I can. I have read many articles about rifaximin and have attended professional presentations. I have also taken it myself. While writing this article, I sounded to myself like I could be a Xifaxan® representative because this post portrays such positive aspects about the drug.  I have nothing to do with Salix Pharmaceuticals and receive no sponsorship. Just wanted you to know that!


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What’s The Right SIBO Diet For You? With so many diet choices out there, it can feel so overwhelming… if you’re not sure where to start, this guide will help you discover exactly which one is right for you.

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