Xifaxan: Uses, Dosage & Side Effects
Rifaximin 550 mg film-coated tablets – antibiotic for preventing recurrent hepatic encephalopathy in adults with liver disease
Quick Facts: Xifaxan (Rifaximin)
Key Takeaways
- Xifaxan (rifaximin) is a gut-selective antibiotic with minimal systemic absorption, used to reduce recurrence of overt hepatic encephalopathy in adults with liver disease.
- The standard dose is one 550 mg tablet taken twice daily by mouth, usually alongside lactulose therapy for optimal effectiveness.
- Rifaximin acts locally in the gastrointestinal tract, reducing ammonia-producing bacteria without significant systemic side effects.
- Serious but rare side effects include Stevens-Johnson syndrome and Clostridioides difficile-associated diarrhea – stop the medication and seek medical attention immediately if these occur.
- Xifaxan is not recommended for children under 18 years and should not be used during pregnancy or breastfeeding.
What Is Xifaxan and What Is It Used For?
Quick Answer: Xifaxan (rifaximin) is a non-absorbable antibiotic that works locally in the gut to reduce ammonia-producing bacteria. It is prescribed for adults with chronic liver disease to prevent recurrent episodes of hepatic encephalopathy – a condition caused by the liver's inability to clear toxins from the blood.
Xifaxan contains the active substance rifaximin, a semisynthetic derivative of rifamycin SV. Unlike most antibiotics that are absorbed into the bloodstream, rifaximin acts almost exclusively within the gastrointestinal tract, with less than 0.4% of an oral dose reaching systemic circulation. This unique pharmacological profile makes it particularly well-suited for treating conditions caused by intestinal bacteria without the widespread systemic effects associated with traditional antibiotics.
Hepatic encephalopathy (HE) is a serious complication of advanced liver disease (cirrhosis) in which the damaged liver cannot adequately detoxify ammonia and other toxins produced by gut bacteria. These toxins accumulate in the bloodstream and cross the blood-brain barrier, leading to a spectrum of neuropsychiatric symptoms. In mild cases, patients may experience subtle cognitive deficits, sleep disturbances, and mood changes. As the condition progresses, more overt symptoms develop, including pronounced confusion, agitation, muscle tremors (asterixis), speech difficulties, disorientation, and in severe cases, coma.
By reducing the population of ammonia-producing bacteria in the intestine, rifaximin helps lower blood ammonia levels, thereby reducing the risk of recurrent HE episodes. Clinical trials have demonstrated that rifaximin significantly reduces the risk of HE recurrence by approximately 58% compared to placebo over a six-month period. The medication is typically used as maintenance therapy to prevent breakthrough episodes, rather than as an acute treatment for ongoing HE episodes.
Xifaxan can be used alone but is more commonly prescribed alongside lactulose, a synthetic disaccharide that acts as an osmotic laxative. Lactulose works by drawing water into the bowel and acidifying the colonic environment, which traps ammonia and promotes its excretion. The combination of rifaximin and lactulose provides a dual mechanism of action: rifaximin reduces ammonia production by bacteria while lactulose enhances ammonia elimination. International guidelines from the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) recommend this combination as the standard of care for secondary prophylaxis of overt HE.
Rifaximin binds to the beta-subunit of bacterial DNA-dependent RNA polymerase, inhibiting bacterial RNA synthesis. Because it is virtually non-absorbed from the gastrointestinal tract, it achieves high local concentrations in the gut lumen while minimizing systemic exposure. This mechanism effectively reduces the load of ammonia-producing organisms in the colon, including both aerobic and anaerobic bacteria.
What Should You Know Before Taking Xifaxan?
Quick Answer: Before taking Xifaxan, tell your doctor about all allergies (especially to rifamycin-type antibiotics), current medications, pregnancy or breastfeeding status, and whether you have any intestinal obstruction. Serious skin reactions and Clostridioides difficile infection are possible risks that require immediate medical attention.
Contraindications
You must not take Xifaxan if you are allergic to rifaximin, similar rifamycin-type antibiotics (such as rifampicin or rifabutin), or any other ingredients in the tablet. A history of hypersensitivity to any rifamycin derivative is an absolute contraindication, as cross-sensitivity reactions can occur within this antibiotic class. Additionally, Xifaxan must not be used if you have an intestinal obstruction (bowel blockage), as the drug requires an intact gastrointestinal tract to function properly and could worsen an existing obstruction.
If you have previously experienced severe skin rashes, skin peeling, blisters, or mouth sores after taking rifaximin or any related medication, inform your doctor immediately, as this may indicate a predisposition to serious dermatological reactions.
Warnings and Precautions
Several important warnings apply when taking Xifaxan. Healthcare providers and patients should be aware of the following precautions:
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with rifaximin treatment. Stop taking Xifaxan and seek emergency medical care immediately if you develop reddish, non-raised, target-shaped or circular patches on the trunk, often with central blisters, skin peeling, sores in the mouth, throat, nose, genitals, or eyes. These skin reactions may be preceded by fever and flu-like symptoms.
Treatment with antibiotics, including rifaximin, can cause severe diarrhea due to Clostridioides difficile (C. difficile) infection. This condition can occur during treatment or even several months after completing a course of antibiotics. If you develop severe or persistent diarrhea during or after Xifaxan use, stop taking the medication and contact your doctor immediately. Do not take anti-diarrheal medications without medical advice, as they may worsen the condition.
Urine discoloration: While taking Xifaxan, your urine may turn reddish in color. This is a harmless pharmacological effect of rifaximin and its metabolites and does not indicate any medical problem. It resolves after discontinuation of the medication.
Severe liver impairment: If your liver disease is severe (Child-Pugh Class C), your doctor may need to monitor you more closely during treatment. Although rifaximin has minimal systemic absorption in healthy individuals, patients with severely impaired liver function may have increased systemic exposure to the drug. Clinical studies have shown that plasma concentrations of rifaximin can be significantly higher in patients with decompensated cirrhosis compared to healthy volunteers. Your doctor will weigh the benefits against potential risks.
Sodium content: Each Xifaxan tablet contains less than 1 mmol sodium (23 mg), meaning the medication is essentially sodium-free. This is relevant for patients on sodium-restricted diets due to their liver condition.
Children and Adolescents
Xifaxan is not recommended for use in children and adolescents under 18 years of age. The safety and efficacy of rifaximin have not been established in the pediatric population through adequate and well-controlled studies. There are no sufficient data to support a dosing recommendation for this age group.
Pregnancy and Breastfeeding
If you are pregnant, think you might be pregnant, or are planning to have a baby, consult your doctor before taking Xifaxan. The effects of rifaximin on the developing fetus are not known. Animal reproduction studies are not always predictive of human response, and there are no adequate and well-controlled studies in pregnant women. As a precautionary measure, Xifaxan should not be used during pregnancy unless the potential benefit is considered to justify the potential risk.
It is not known whether rifaximin or its metabolites are excreted in human breast milk. Because many drugs are excreted in human milk, and because of the potential for adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the medication for the mother. Xifaxan should therefore not be used while breastfeeding.
Driving and Using Machines
Xifaxan does not normally affect the ability to drive or use machines. However, some patients may experience dizziness as a side effect. If you feel dizzy after taking Xifaxan, you should not drive or operate machinery until the symptom resolves. It is also important to note that the underlying condition (hepatic encephalopathy) itself can significantly impair cognitive function and reaction times, which should be taken into account independently of the medication.
How Does Xifaxan Interact with Other Drugs?
Quick Answer: Although rifaximin has minimal systemic absorption, it can interact with several important medications including warfarin, ciclosporin, antiepileptics, antiarrhythmics, and oral contraceptives. Always inform your doctor about all medications you are currently taking, including over-the-counter medicines and herbal products.
Drug interactions with rifaximin are generally considered less clinically significant than those associated with systemically absorbed rifamycins like rifampicin. However, because rifaximin shares structural similarities with other rifamycins and has some potential for inducing cytochrome P450 enzymes, certain interactions warrant attention and monitoring.
Rifaximin is a substrate and a weak inducer of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp). In patients with normal liver function, where systemic absorption is minimal, these interactions are unlikely to be clinically relevant. However, in patients with hepatic impairment – the primary population for whom Xifaxan is prescribed – higher systemic exposure may increase the potential for drug-drug interactions.
| Medication | Interaction Type | Clinical Significance | Recommendation |
|---|---|---|---|
| Warfarin | CYP enzyme interaction | May alter anticoagulant effect; INR changes possible | Monitor INR closely; dose adjustment may be needed |
| Ciclosporin | P-glycoprotein / CYP3A4 interaction | Ciclosporin may increase rifaximin plasma levels significantly | Use with caution; monitor for increased rifaximin effects |
| Oral Contraceptives | Potential CYP3A4 induction | Possible reduced contraceptive efficacy | Consider additional contraceptive measures |
| Antiepileptics | CYP enzyme interaction | Altered plasma levels of some antiepileptic drugs | Monitor seizure control and drug levels |
| Antiarrhythmics | CYP enzyme interaction | Potential altered antiarrhythmic drug levels | Monitor cardiac rhythm and drug levels |
| Other Antibiotics | Pharmacodynamic | May alter gut microbiome effects of rifaximin | Inform your doctor about concurrent antibiotic use |
In a notable pharmacokinetic study, co-administration of ciclosporin (a potent P-glycoprotein inhibitor) with a single dose of rifaximin 550 mg resulted in an approximately 83-fold increase in rifaximin systemic exposure (AUC) and a 124-fold increase in peak plasma concentration (Cmax). While the clinical significance of this finding in the context of chronic use remains under investigation, caution is warranted when Xifaxan is prescribed to patients already receiving ciclosporin or other potent P-glycoprotein inhibitors.
Herbal supplements and over-the-counter products can also interact with prescription medications. Always inform your healthcare provider about all products you are using, including vitamins, minerals, and dietary supplements, to ensure safe and effective treatment.
What Is the Correct Dosage of Xifaxan?
Quick Answer: The recommended dose of Xifaxan for preventing recurrent hepatic encephalopathy is one 550 mg tablet taken twice daily (morning and evening) with a glass of water. Treatment should continue for as long as your doctor prescribes.
Xifaxan should always be taken exactly as prescribed by your doctor. If you are unsure about any aspect of your dosing regimen, consult your doctor or pharmacist for clarification. The duration of treatment is determined by your prescribing physician and is typically long-term maintenance therapy.
Adults
Standard Adult Dose
Dose: 550 mg (one tablet) twice daily
Route: Oral, with a glass of water
Timing: Approximately 12 hours apart (e.g., morning and evening)
Food: Can be taken with or without food
Duration: As directed by your doctor (typically long-term maintenance)
The total daily dose is 1,100 mg (two tablets of 550 mg). Clinical studies supporting the efficacy of rifaximin for HE prevention used this dosing regimen. Xifaxan is most commonly prescribed alongside lactulose therapy. Your doctor may adjust your lactulose dose separately to achieve two to three soft bowel movements per day.
Children and Adolescents
Pediatric Dose
Not recommended for patients under 18 years of age. Safety and efficacy have not been established in this population. No dosing recommendation can be made.
Elderly Patients
No specific dose adjustment is required for elderly patients. The standard dose of 550 mg twice daily applies. However, elderly patients with liver disease should be monitored closely, as they may have additional comorbidities and concurrent medications that could affect treatment outcomes. Renal impairment, which is more common in elderly patients, does not require dose adjustment since rifaximin has negligible renal excretion.
Missed Dose
If you miss a dose, take the next dose at the usual scheduled time. Do not take a double dose to make up for a forgotten tablet. Maintaining a consistent dosing schedule is important for optimal prevention of HE episodes, so try to take your tablets at the same times each day to establish a routine.
Overdose
If you take more Xifaxan than prescribed, or if someone (such as a child) accidentally ingests the medication, contact your doctor, hospital, or a poison control center immediately for an assessment of the risk and appropriate advice. In clinical trials, doses up to 2,400 mg per day have been administered without significant safety concerns beyond those seen at the recommended dose. However, any suspected overdose should be evaluated by a healthcare professional. Treatment of overdose is supportive, as there is no specific antidote for rifaximin.
Do not stop taking Xifaxan without first talking to your doctor. Abrupt discontinuation of maintenance therapy may increase the risk of HE recurrence. Your doctor will advise you on the appropriate duration of treatment and any necessary tapering strategies.
What Are the Side Effects of Xifaxan?
Quick Answer: Like all medicines, Xifaxan can cause side effects, though not everyone gets them. Common side effects include dizziness, headache, nausea, abdominal pain, and diarrhea. Serious but rare side effects include severe skin reactions (SJS/TEN), C. difficile-associated diarrhea, and severe allergic reactions.
The side effect profile of Xifaxan is generally favorable due to its minimal systemic absorption. Most adverse reactions reported during clinical trials and post-marketing surveillance are gastrointestinal in nature and tend to be mild to moderate in severity. However, as with any medication, serious adverse reactions can occur, and patients should be aware of the warning signs.
Bleeding from swollen blood vessels in the throat (esophageal varices); severe diarrhea during or after treatment (possible C. difficile infection); signs of Stevens-Johnson syndrome or toxic epidermal necrolysis (skin blisters, peeling, mouth sores); allergic reactions including facial swelling, difficulty swallowing, hives, or breathing difficulties; unexpected or unusual bleeding or bruising.
Common
May affect up to 1 in 10 people
- Depression or low mood
- Dizziness
- Headache
- Shortness of breath (dyspnea)
- Nausea or vomiting
- Abdominal pain or bloating
- Diarrhea
- Fluid accumulation in the abdomen (ascites)
- Rash or itching
- Muscle cramps
- Joint pain (arthralgia)
- Swollen ankles, feet, or fingers (peripheral edema)
Uncommon
May affect up to 1 in 100 people
- Yeast infections (e.g., oral thrush or vaginal candidiasis)
- Urinary tract infections (e.g., cystitis)
- Anemia (low red blood cell count)
- Loss of appetite
- Hyperkalemia (high potassium levels in the blood)
- Confusion or disorientation
- Anxiety
- Drowsiness or excessive sleepiness
- Difficulty sleeping (insomnia)
- Feeling unsteady or off-balance
- Memory loss or poor memory
- Decreased concentration
- Decreased sensation (hypoesthesia)
- Seizures (convulsions)
- Hot flushes
- Pleural effusion (fluid around the lungs)
- Dry mouth
- Abdominal pain
- Muscle pain (myalgia)
- Increased urinary frequency
- Painful or difficult urination (dysuria)
- Fever
- Edema (general swelling)
- Falls
- Bleeding from esophageal varices
Rare
May affect up to 1 in 1,000 people
- Lower respiratory tract infections (including pneumonia)
- Cellulitis (skin and soft tissue infection)
- Upper respiratory tract infections (nose, mouth, throat)
- Rhinitis (nasal inflammation)
- Dehydration
- Blood pressure changes
- Persistent breathing problems (e.g., chronic bronchitis)
- Constipation
- Back pain
- Proteinuria (protein in the urine)
- Weakness or fatigue
- Bruising
- Post-surgical pain
Not Known
Frequency cannot be estimated from available data
- Stevens-Johnson syndrome / toxic epidermal necrolysis (serious skin reactions)
- Allergic reactions, hypersensitivity, or angioedema
- Fainting or feeling faint (syncope)
- Skin irritation, eczema (itchy, red, dry skin)
- Decreased platelet count (thrombocytopenia)
- Altered liver function (detected via blood tests)
- Changes in blood coagulation / INR values (detected via blood tests)
It is important to distinguish between side effects caused by Xifaxan and symptoms of the underlying liver disease or hepatic encephalopathy itself. Many of the listed side effects, particularly ascites, peripheral edema, confusion, and esophageal variceal bleeding, are also common manifestations of advanced liver disease. Your doctor will help determine whether symptoms are medication-related or disease-related.
If you experience any side effects not listed here, or if any of the listed side effects become severe or persistent, talk to your doctor or pharmacist. Reporting suspected adverse reactions contributes to the ongoing monitoring of the benefit-risk balance of the medication.
How Should You Store Xifaxan?
Quick Answer: Store Xifaxan out of the sight and reach of children, at room temperature with no special storage requirements. Do not use after the expiry date printed on the packaging.
Keep Xifaxan out of the sight and reach of children at all times to prevent accidental ingestion. Store the tablets in their original packaging (blister pack inside the carton) to protect them from moisture and light.
There are no special temperature storage requirements for Xifaxan. However, as a general recommendation, store the medication at room temperature (below 25°C / 77°F) and avoid exposure to excessive heat or humidity. Do not store medications in the bathroom or near a kitchen sink.
Do not use Xifaxan after the expiry date (marked "EXP" on the carton and blister pack). The expiry date refers to the last day of the stated month. Once expired, medications may lose effectiveness and could potentially pose safety risks.
Do not dispose of medications via household waste or down the drain. Ask your pharmacist about proper medication disposal programs in your area. Appropriate disposal helps protect the environment and prevents accidental exposure.
What Does Xifaxan Contain?
Quick Answer: Each Xifaxan tablet contains 550 mg of rifaximin as the active ingredient, with inactive excipients in the tablet core and a film-coating containing hypromellose, titanium dioxide, and iron oxide pigments.
Each Xifaxan film-coated tablet contains 550 mg of rifaximin as the active substance. Rifaximin is a semisynthetic, nonsystemic antibiotic derived from rifamycin SV, with the molecular formula C43H51N3O11.
Inactive Ingredients
Tablet core: Sodium starch glycolate (type A), glycerol distearate, colloidal anhydrous silica, talc, microcrystalline cellulose.
Film-coating (Opadry OY-S-34907): Hypromellos, titanium dioxide (E171), disodium edetate, propylene glycol, red iron oxide (E172).
Appearance
Xifaxan tablets are pink, oval, biconvex, film-coated tablets embossed with "RX" on one side. They are available in cartons containing 14, 28, 42, 56, or 98 tablets in blister packs. Not all pack sizes may be marketed in all countries.
Brand Names by Country
Rifaximin 550 mg is marketed under different brand names across Europe and internationally:
| Country | Brand Name |
|---|---|
| United States | Xifaxan |
| Germany, Denmark, Norway, Sweden, Netherlands | Xifaxan |
| Belgium, Finland, Ireland, Luxembourg | Targaxan |
The marketing authorization holder is Norgine B.V. (Amsterdam, Netherlands). The tablets are manufactured by Alfasigma S.p.A. at production facilities in Alanno (Pescara) and Pomezia (Rome), Italy.
Frequently Asked Questions About Xifaxan
Xifaxan (rifaximin) is an antibiotic used in adults with liver disease (cirrhosis) to reduce the recurrence of episodes of overt hepatic encephalopathy. Hepatic encephalopathy is a condition where the liver cannot adequately remove toxins from the blood, causing neuropsychiatric symptoms such as confusion, agitation, speech problems, and in severe cases, loss of consciousness. Xifaxan works locally in the gut to reduce ammonia-producing bacteria and is typically used alongside lactulose therapy.
Rifaximin is unique among antibiotics because it is virtually non-absorbed from the gastrointestinal tract – less than 0.4% of an oral dose enters the bloodstream. This means it works almost exclusively within the gut, targeting intestinal bacteria without the widespread systemic effects common to most antibiotics. This property greatly reduces the risk of systemic side effects and drug interactions while achieving very high antibiotic concentrations where they are needed most.
Yes, Xifaxan is commonly prescribed together with lactulose. In fact, this combination is considered the standard of care for preventing recurrent hepatic encephalopathy according to guidelines from both the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL). While lactulose helps trap and eliminate ammonia from the bowel, rifaximin reduces the production of ammonia by gut bacteria, providing complementary mechanisms of action.
A reddish discoloration of urine is a known and harmless effect of rifaximin and is related to the drug's chemical structure as a rifamycin derivative. The red-orange pigmentation comes from the metabolites of the drug being excreted in small amounts through the kidneys. This is not a sign of blood in the urine and does not indicate any medical problem. The color returns to normal after you stop taking the medication.
Xifaxan is typically prescribed as a long-term maintenance therapy for preventing recurrent hepatic encephalopathy. You should continue taking the medication until your doctor advises you to stop. The duration depends on your individual clinical situation, including the severity of your liver disease, your response to treatment, and the frequency of HE episodes. Do not stop taking Xifaxan without consulting your doctor, as discontinuation may increase the risk of HE recurrence. Long-term studies have shown that rifaximin maintains its effectiveness and safety profile over extended treatment periods of up to 24 months and beyond.
Resistance development with rifaximin appears to be minimal compared to systemically absorbed antibiotics. Studies have shown that while some gut bacteria can develop reduced susceptibility to rifaximin during treatment, this resistance tends to be unstable and reversible upon discontinuation of the drug. Additionally, because rifaximin acts locally in the gut and has a broad spectrum of activity against multiple bacterial species, the clinical impact of resistance development is considered limited. Long-term studies over 24 months have not shown a significant loss of clinical efficacy.
References
- European Medicines Agency (EMA). Xifaxan (rifaximin) Summary of Product Characteristics. Last updated 2025.
- U.S. Food and Drug Administration (FDA). Xifaxan (rifaximin) Prescribing Information. Salix Pharmaceuticals, 2024.
- Bass NM, Mullen KD, Sanyal A, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362(12):1071-1081. doi:10.1056/NEJMoa0907893
- Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014;60(2):715-735.
- European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines on the management of hepatic encephalopathy. J Hepatol. 2022;77(3):807-824.
- 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.
- Kimer N, Krag A, Møller S, Bendtsen F, Gluud LL. Systematic review with meta-analysis: the effects of rifaximin in hepatic encephalopathy. Aliment Pharmacol Ther. 2014;40(2):123-132.
- World Health Organization (WHO). WHO Model List of Essential Medicines, 23rd edition, 2023.
- British National Formulary (BNF). Rifaximin. National Institute for Health and Care Excellence (NICE), 2025.
- Bajaj JS. Hepatic encephalopathy: classification and treatment. J Hepatol. 2018;68(4):838-839.
Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, comprising licensed specialist physicians with expertise in gastroenterology, hepatology, and clinical pharmacology.
Medical Writer
Licensed physician with specialist training in gastroenterology and hepatology. Experienced in translating complex medical information into patient-friendly content.
Medical Reviewer
Board-certified hepatologist with clinical experience in managing hepatic encephalopathy and chronic liver disease. Reviews content for clinical accuracy.
Pharmacology Advisor
Clinical pharmacologist with expertise in drug interactions, pharmacokinetics, and medication safety in patients with hepatic impairment.
Editorial Standards
All content follows the GRADE evidence framework and is based on peer-reviewed research, international guidelines (AASLD, EASL, EMA, FDA), and established medical consensus.
All medical content on iMedic follows the GRADE evidence framework. No commercial funding or pharmaceutical sponsorship influences our editorial process. Last fact-checked: December 23, 2025.