What you need to know about taking Xifaxan (Rifaximin) to treat your SIBO - Gut Professor (2023)

If you’ve been prescribed Xifaxan® (Rifaximin) for small intestinal bacterial overgrowth (SIBO) then you aren’t alone. It’squicklybecoming the most commonly used treatment by doctors around the world. However, it’sstill 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 carephysician to prescribe it. Then I filled the prescription and it sat on my counter for anotherweek 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 sayingwhether you take it or not I hope that this article at least helps you make the right decisionfor 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’sdiarrhea.1However, 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 thebest treatment for SIBO among patients with IBS.”2

Throughout this article, I will refer to rifaximin since the majority of researchers use thisform in their studies. Rifaximin is a broad-spectrum antibiotic, meaning that it kills differenttypes 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 verystrong positive for rifaximin compared to other antibiotics.

Just to give you some perspective, according to the monograph on penicillin V (a class ofpenicillin antibiotic), 25-73% of it is absorbed from the gastrointestinal tract into thesystemic 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 elsequite like it. It’s interesting properties of not being absorbed is what makes it so helpful intreating infections directly involving the GI tract, like IBS and SIBO, with less risks of sideeffects.

How Rifaximin Works in the Body

Rifaximin is so good at treating SIBO because it does its job in the small intestine andnowhere else. That is why it is becoming so popular in treating SIBO. But besides killingbacteria, 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 antibioticshave 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 feelingbetter not only because it’s reducing the overgrowth in your small intestine, but it’s alsofighting 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 tobegin with. Now you are being told by your doctor to turn around and take an antibiotic totreat it. That doesn’t sound right!

When penicillin was introduced in the 1940’s, it revolutionized how medicine waspracticed. Antibiotics are powerful drugs that can save lives; however, they also carryrisks. Side effects of antibiotics can be mild to life threatening. It can be scary when youare 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 142,505visits to the ER that occurred in 2004-2006,19.3% of them were associated with systemicantibiotics.8

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

In addition, all other antibiotics that have been studied reduce the abundance of bacteria inthe intestinal tract by 30% and sometimes, the microbial community may not totallyrecover. Alterations in the bacteria can last for months to years.6

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 werebeing treated with rifaximin. Reported adverse events was 4.6% overall-that is pretty lowcompared to systemic antibiotics.7 Of those 17 studies, I looked up the study that wasshown to have the highest adverse events (14/80 participants-17.5%) just to see what theactual symptoms were.9 Indigestion and constipation were the two most frequentlyreported 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 dosagewas 550 mg twice per day to treat people with chronic liver problems. The authors foundthat the patients treated with rifaximin long term had decreased hospital admissionswithout 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 anincrease in GI symptoms and fatigue. This could be due to the herxheimer reaction, whichis a short-term detoxification reaction associated with large numbers of microorganismsdying at once.

One of my patients reported an increase in heart rate within a few hours of taking rifaximinand in that situation, it was recommended that she stop taking it. For a more complete listof 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 ofdeveloping a really dreadful condition called Clostridium difficile infection (CDI). You maynot have heard about this infection, but I saw a lot of it while working in the hospital settingand it was pretty scary. C. difficile is a bacterium that colonizes in the colon and canproduce harmful toxins, leading to colitis (inflammation of the colon). It can be difficult toeradicate and can become resistant to the usual treatment. It is most commonlyassociated with systemic antibiotic use, because antibiotics kill the good bacteria in thecolon 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 beentreated with rifaximin. On average, they were treated for 250 days at doses ranging from800 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 hadfinished taking 1200 mg of rifaximin for 4 weeks to treat SIBO.12 The authors failed tomention how much time had elapsed from the start of the infection to when the participanthad stopped the rifaximin, as well as any risk factors associated with developing thisinfection. Nevertheless, there have been other accounts of a few patients with liverdisease 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 thetreatment 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 ofgetting CDI when taking rifaximin to treat your SIBO. But studies show that the risk is lowcompared to the systemic antibiotics, so that is a positive. And again, it is used to actuallytreat the infection.

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

Antibiotics and Bacterial Resistance

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

Bacterial resistance happens when antibiotics are overused, misused and are sowidespread, 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 millionAmericans are infected with these drug resistant strains of bacteria and thousands diefrom 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 afterbeing treated for 12 weeks.16 Although some researchers caution that more studies needto 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 thatwe can to enhance its effectiveness while we are taking it. See the section “What should Ido 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 Ibecame about rifaximin, the less worried I was about taking it.

But you may be wondering, how well does it work? Researchers analyzed 36 studiesincluding 1331 participants and reported that the eradication rates of rifaximin for SIBOwas approximately 71-73%. The higher the dosage, the better the results were.7

The same researchers reviewed ten studies that measured symptoms before and aftertreatment with rifaximin. Approximately 68% of participants whose SIBO was eradicatedreported 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 itdoesn’t work for everyone.

My Experience Taking Rifaximin

I made the decision to take rifaximin because I needed something stronger than the herbsthat I had been taking to treat my SIBO. I was still searching for my underlying causes andneeded some symptom relief! At the time that I went on rifaximin, I could barely breathebecause 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’thave 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 biggestproblem 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 youexpected.

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 outwhat 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% chanceof killing SIBO.

The Biggest Problem with Rifaximin

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

Xifaxan® was approved by the FDA to treat IBS with diarrhea in 2015, which has helpedpatients get better insurance coverage. If your insurance denies coverage and you areunable 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 andexpect symptoms to just melt away and never come back, without addressing many otherfactors.

Since this article is about the safety of rifaximin, I didn’t mention the relapse rate, but it canbe high. This is common for SIBO, whatever treatment you are using. Once you finishtaking the rifaximin, you’re not done. You will need to take the necessary steps to preventrelapse. 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 comfortableabout 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 acomprehensive 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 treatmentoptions. 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. Ihave read many articles about rifaximin and have attended professional presentations. Ihave also taken it myself. While writing this article, I sounded to myself like I could be aXifaxan® representative because this post portrays such positive aspects about the drug. I have nothing to do with Salix Pharmaceuticals and receive no sponsorship. Just wantedyou to know that!


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  6. Francino MP. Antibiotics and the human gut microbiome: Dysbioses and accumulation of resistances. Front Microbiol. 2016;6:1-11. doi:10.3389/fmicb.2015.01543.
  7. Gatta L, Scarpignato C. Systematic review with meta-analysis: rifaximin is effective and safe for the treatment of small intestine bacterial overgrowth. Aliment Pharmacol Ther. 2017;45(5):604-616. doi:10.1111/apt.13928.
  8. Geller A, Shehab N. Emergency department visits for adverse events related to dietary supplements. N Engl J Med. 2015;373(16):1531-1540. http://www.nejm.org/doi/pdf/10.1056/NEJMsa1504267. Accessed January 16, 2016.
  9. Scarpellini E, Gabrielli M, Lauritano CE, et al. High dosage rifaximin for the treatment of small intestinal bacterial overgrowth. Aliment Pharmacol Ther. 2007;25(7):781-786. doi:10.1111/j.1365-2036.2007.03259.x.
  10. Mullen KD, Sanyal AJ, Bass NM, et al. Rifaximin is safe and well tolerated for long-term maintenance of remission from overt hepatic encephalopathy. Clin Gastroenterol Hepatol. 2014;12(8):1390-1397.e2. doi:10.1016/J.CGH.2013.12.021.
  11. Neff GW, Jones M, Jonas M, et al. Lack of Clostridium difficile infection in patients treated with rifaximin for hepatic encephalopathy. J Clin Gastroenterol. 2013;47(2):188-192. doi:10.1097/MCG.0b013e318276be13.
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