What You Should Know About Rifaximin Side Effects

Rifaximin (brand name Xifaxan) is generally well-tolerated because very little of it is absorbed into your bloodstream — less than 0.4% reaches your system. It works locally in your gut, which means fewer body-wide side effects compared to many other antibiotics. But like any medication, it can cause side effects in some people.

This guide covers the most common side effects, the rare but serious ones to watch for, and when you should contact your doctor.

What Is Rifaximin?

Rifaximin is a non-absorbable antibiotic in the rifamycin class. It's FDA-approved for three conditions: travelers' diarrhea (200 mg three times daily for 3 days), hepatic encephalopathy prevention (550 mg twice daily, ongoing), and IBS with diarrhea (550 mg three times daily for 14 days). It's manufactured by Salix Pharmaceuticals, a subsidiary of Bausch Health.

Common Side Effects

The following side effects were reported in clinical trials and are considered common. Most are mild and tend to improve as your body adjusts:

• Nausea — One of the most frequently reported side effects, usually mild
• Stomach pain — Abdominal discomfort or cramping
• Dizziness — May occur especially in the first few days
• Fatigue — Feeling tired or low-energy
• Headache — Common across all three approved uses
• Muscle tightening — Muscle spasms or stiffness
• Joint pain — Mild aches in joints
• Reddish discoloration of urine — This is harmless and expected with rifamycin-class drugs. It does not mean anything is wrong with your kidneys.

These side effects are generally mild and temporary. Most people taking Rifaximin don't experience side effects severe enough to stop the medication.

Serious Side Effects

Serious side effects are rare with Rifaximin, but they do exist. Contact your doctor right away if you experience any of the following:

• Clostridioides difficile-associated diarrhea (C. diff) — Severe, watery diarrhea that doesn't stop, possibly with fever and stomach cramps. This can occur with nearly any antibiotic and may develop even after you stop taking the medication.
• Drug-resistant bacterial superinfection — Signs include worsening symptoms, new fever, or symptoms that return after initially improving.
• Severe allergic reaction — Hives, rash, itching, swelling of the face or throat, difficulty breathing, or chest tightness. Seek emergency medical help immediately if this occurs.

Rifaximin carries no boxed warning from the FDA, which is notable for an antibiotic. This reflects its relatively favorable safety profile.

Side Effects in Specific Populations

Liver Disease Patients

If you're taking Rifaximin for hepatic encephalopathy, you likely have underlying liver disease. Patients with severe hepatic impairment (Child-Pugh Class C) may absorb more Rifaximin into their bloodstream than healthy individuals, which could increase the risk of systemic side effects. Your doctor will monitor you more closely in this case.

Pregnancy and Breastfeeding

Rifaximin is Pregnancy Category C, meaning animal studies have shown potential harm to the fetus. It should be avoided during pregnancy and breastfeeding unless the benefit clearly outweighs the risk. Talk to your doctor about alternatives if you're pregnant or planning to become pregnant.

Children

Rifaximin is approved for travelers' diarrhea in children 12 and older. Safety has not been established in children under 12, or in anyone under 18 for hepatic encephalopathy or IBS-D.

How to Manage Common Side Effects

Most Rifaximin side effects are manageable with simple steps:

• Nausea — Take with a small meal or snack. Rifaximin can be taken with or without food, but eating may help settle your stomach.
• Dizziness — Avoid driving or operating machinery until you know how the medication affects you. Stand up slowly from sitting or lying positions.
• Fatigue — Rest when needed. This usually improves within the first week.
• Headache — Over-the-counter pain relievers like Acetaminophen (Tylenol) are generally safe to take with Rifaximin, but check with your doctor first.
• Red urine — No treatment needed. This is a normal effect of rifamycin-class antibiotics and will stop when you finish the medication.

If any side effect persists for more than a few days or gets worse, contact your doctor. Don't stop taking Rifaximin without talking to your provider first, especially if you're taking it for hepatic encephalopathy — stopping suddenly could lead to a recurrence.

When to Call Your Doctor

Call your doctor if you experience:

1. Severe or bloody diarrhea
2. Fever above 101°F while taking Rifaximin
3. Symptoms that get worse instead of better
4. Any signs of an allergic reaction
5. New or worsening confusion (especially for hepatic encephalopathy patients)

For severe allergic reactions (difficulty breathing, throat swelling), call 911 or go to the nearest emergency room.

Final Thoughts

Rifaximin has a strong safety profile compared to many antibiotics because it stays in your gut rather than spreading throughout your body. Most side effects are mild — nausea, stomach pain, headache — and tend to go away on their own. Serious side effects are rare but worth knowing about.

If you're concerned about side effects or want to learn more about how Rifaximin works, check out our guide on Rifaximin's mechanism of action. And if cost is a concern, we've put together a comprehensive guide on saving money on Rifaximin.