Rifaximin Drug Interactions You Should Know About

Rifaximin (brand name Xifaxan) has fewer drug interactions than most antibiotics because less than 0.4% of it enters your bloodstream. But "fewer" doesn't mean "none." Certain medications, especially in patients with liver disease, can interact with Rifaximin in ways that matter. Here's what you need to know.

How Drug Interactions Work with Rifaximin

Most drug interactions happen when two medications compete for the same metabolic pathways in the body — typically enzymes in the liver or transport proteins in the gut. Because Rifaximin is barely absorbed in healthy patients, these interactions are usually minimal.

However, in patients with severe hepatic impairment (Child-Pugh Class C), Rifaximin absorption can increase significantly. This is important because many of the people taking Rifaximin for hepatic encephalopathy already have advanced liver disease. In these patients, the drug interactions listed below become more clinically relevant.

Major Drug Interactions

Warfarin (Coumadin)

Rifaximin may decrease the effectiveness of Warfarin in patients with hepatic impairment. If you take Warfarin for blood clots, atrial fibrillation, or another condition, your doctor should monitor your INR (a measure of blood clotting) more frequently when starting or stopping Rifaximin. Dose adjustments may be needed.

CYP3A4 Substrates

In patients with liver disease where Rifaximin absorption is higher, there's a potential interaction with medications metabolized by the CYP3A4 enzyme. Common CYP3A4 substrates include:

• Midazolam (Versed) — a sedative
• Simvastatin (Zocor) — a cholesterol medication
• Amlodipine (Norvasc) — a blood pressure medication
• Certain immunosuppressants — like Tacrolimus and Sirolimus

If you take any of these and have liver disease, tell your doctor. They may need to adjust dosing or monitor drug levels more closely.

P-Glycoprotein Inhibitors

Cyclosporine (Sandimmune, Neoral) is the most notable interaction here. Cyclosporine inhibits P-glycoprotein, a transport protein that normally pumps Rifaximin back into the gut. When P-glycoprotein is blocked, more Rifaximin enters the bloodstream — potentially increasing systemic side effects. In clinical studies, co-administration with Cyclosporine increased Rifaximin blood levels by approximately 83-fold.

If you take Cyclosporine (common after organ transplantation), your doctor needs to know before prescribing Rifaximin.

Moderate Drug Interactions

Live Vaccines

Like other antibiotics, Rifaximin may reduce the effectiveness of live vaccines. The most relevant example is the oral typhoid vaccine (Vivotif), which contains live bacteria. If you're planning travel and need this vaccine, talk to your doctor about timing — ideally, complete the vaccine series before starting Rifaximin.

Inactivated vaccines (flu shots, COVID boosters, etc.) are not affected.

Supplements and OTC Medications to Watch

Rifaximin has relatively few interactions with over-the-counter products, but it's still worth mentioning a few:

• Probiotics — There's no established harmful interaction, but taking an antibiotic alongside probiotics may reduce the effectiveness of either. Many doctors recommend waiting until after your Rifaximin course to start probiotics, or taking them at least 2 hours apart.
• Herbal supplements that affect liver enzymes — St. John's Wort, for example, is a strong CYP3A4 inducer and could theoretically affect Rifaximin metabolism in patients with liver disease. Mention all supplements to your doctor.
• Antacids and acid reducers — No significant interaction is expected, but if you take proton pump inhibitors (like Omeprazole) or H2 blockers (like Famotidine), mention them to your pharmacist for a complete interaction check.

Food and Drink Interactions

Good news here: Rifaximin has no significant food interactions. You can take it with or without food, and there are no dietary restrictions while on the medication. Unlike Metronidazole (Flagyl), Rifaximin does not interact with alcohol — though if you have liver disease, your doctor has likely already advised limiting alcohol for other reasons.

What to Tell Your Doctor

Before starting Rifaximin, give your doctor a complete list of everything you take:

• All prescription medications — especially blood thinners, immunosuppressants, and cholesterol drugs
• Over-the-counter medications — including antacids, pain relievers, and allergy medications
• Supplements and vitamins — including herbal products like St. John's Wort, turmeric, and probiotics
• Your liver function status — if you have cirrhosis or advanced liver disease, interactions become more significant

Also tell your doctor if you've recently received or plan to receive any live vaccines.

For more about Rifaximin's side effects and safety profile, see our Rifaximin side effects guide. For a general overview of the drug, check out What Is Rifaximin?

Final Thoughts

Rifaximin's minimal absorption makes it one of the safer antibiotics when it comes to drug interactions — for most patients. The exceptions are people with advanced liver disease, who may absorb more of the drug, and anyone taking Cyclosporine or Warfarin. The bottom line: always share your full medication list with your doctor, and don't assume that a "gut-only" antibiotic can't interact with your other treatments.

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