Rifaximin

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Xifaxan: 200 mg [contains edetate disodium]

Xifaxan: 550 mg

Pharmacology

Mechanism of Action

Rifaximin inhibits bacterial RNA synthesis by binding to bacterial DNA-dependent RNA polymerase.

Pharmacokinetics/Pharmacodynamics

Absorption

Oral:

Travelers' diarrhea: Low

Hepatic encephalopathy: Increased absorption in patients with Child-Pugh class C compared with patients with Child-Pugh class A

Metabolism

Extensive, mainly by CYP3A

Excretion

Feces (96.6% primarily as unchanged drug); urine (0.32%)

Time to Peak

Healthy subjects and patients with IBS without constipation: ~1 hour

Half-Life Elimination

Healthy subjects: 5.6 hours; IBS without constipation: 6 hours

Protein Binding

Healthy subjects: 67.5%; Hepatic impairment: 62%

Use in Specific Populations

Special Populations: Hepatic Function Impairment

The mean AUC in patients with hepatic impairment of Child-Pugh class A, B, and C was 10-, 14-, and 21-fold higher, respectively, compared with that of healthy subjects.

Use: Labeled Indications

Hepatic encephalopathy: Reduction in the risk of overt hepatic encephalopathy recurrence in adults.

Irritable bowel syndrome without constipation: Treatment of moderate to severe irritable bowel syndrome without constipation in adults.

Travelers' diarrhea: Treatment of travelers' diarrhea caused by noninvasive strains of Escherichia coli in adults and pediatric patients ≥12 years of age.

Limitations of use: Rifaximin should not be used in patients with diarrhea complicated by fever or blood in the stool or diarrhea caused by pathogens other than E. coli.

Use: Off Label

Clostridioides (formerly Clostridium) difficile infection (second or subsequent recurrence)byes

Data from a randomized, double-blind, placebo-controlled pilot study support the use of rifaximin to prevent recurrent diarrhea in patients with Clostridioides (formerly Clostridium) difficile infection Garey 2011.

Based on the

Hepatic encephalopathy, treatmentyes

Based on the American Association for the Study of Liver Diseases (AASLD) practice guideline for hepatic encephalopathy, rifaximin may be added to lactulose therapy for the treatment of overt hepatic encephalopathy.

Small intestinal bacterial overgrowthc

Data from a limited number of patients studied suggest rifaximin may be beneficial for the treatment of small intestinal bacterial overgrowth

Travelers’ diarrhea, prophylaxisbyes

Data from a randomized, double-blind, placebo-controlled study support the use of rifaximin to prevent travelers’ diarrhea DuPont 2005.

Based on the

Contraindications

Hypersensitivity to rifaximin, other rifamycin antibiotics, or any component of the formulation

Dosage and Administration

Dosing: Adult

Note: The 200 mg tablet may not be available in some international markets; consult local product labeling for availability.

Clostridioides (formerly Clostridium) difficile infection (second or subsequent recurrence) (alternative regimen) (off-label use): Oral: 400 mg 3 times daily for 20 days; administer after a 10-day course of oral vancomycin (Garey 2011; IDSA/SHEA [McDonald 2018]; Johnson 2007).

Hepatic encephalopathy, treatment (off-label use) or chronic prevention of recurrence: Note: Use as an adjunct or alternative to nonabsorbable disaccharides (eg, lactulose) in patients intolerant of or with insufficient response to disaccharides (AASLD [Vilstrup 2014]; Ferenci 2019).

Oral: 400 mg 3 times daily or 550 mg twice daily (AASLD [Vilstrup 2014]; Ferenci 2019; Mohammad 2012; Puxeddu 1995). When used for treatment of an acute episode, may be given for 5 to 10 days (Mas 2003).

Irritable bowel syndrome, moderate to severe, without constipation (alternative agent): Note: Reserve for patients, particularly those with bloating, who have failed other therapies (Lembo 2016; Pimentel 2011; Wald 2019).

Oral: 550 mg 3 times daily for 14 days (Lembo 2016; Pimentel 2011; Wald 2019).

Small intestinal bacterial overgrowth (off-label use): Oral: 550 mg 3 times daily for 14 days (Pimentel 2019; Scarpellini 2007). For patients with methane-predominant bacterial overgrowth, some experts use rifaximin as part of an appropriate combination regimen (Pimentel 2019).

Travelers’ diarrhea:

Prophylaxis (off-label use): Note: Routine prophylaxis is not recommended. Reserve for select short-term travelers (eg, <2 weeks) at high risk of complications from diarrheal illness. Effectiveness for travelers to South and Southeast Asia may be reduced (Riddle 2017).

Oral: 200 mg 1 to 3 times daily for the duration of travel; optimal dose and duration not well established (DuPont 2005; Hu 2012; LaRocque 2019; Steffen 2015).

Treatment, moderate to severe (alternative agent): Note: Avoid in patients with fever or bloody diarrhea (Riddle 2017).

Oral: 200 mg 3 times daily for 3 days (Riddle 2017).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Diarrhea, travelers’: Oral: Note: Efficacy has not been established for the treatment of diarrhea due to pathogens other than E. coli, including C. jejuni, Shigella, and Salmonella; avoid use in diarrhea with fever or blood in the stool; consider alternative therapy if symptoms persist or worsen after 24 to 48 hours of treatment

Children 3 to 11 years: Limited data available: 100 mg 4 times daily for up to 5 days has been used in 38 children (age range: 3 to 8 years) to treat infectious diarrhea (Beseghi 1998; Frisari 1997)

Children ≥12 years and Adolescents: 200 mg 3 times daily for 3 days

Hepatic encephalopathy: Oral: Adolescents ≥18 years: Reduction of overt hepatic encephalopathy recurrence: 550 mg 2 times daily

Inflammatory bowel disease (IBD) (Crohn disease, ulcerative colitis): Limited data available: Oral: Children ≥8 years and Adolescents: 10 to 30 mg/kg/day in divided doses; maximum daily dose: 1200 mg/day. Dosing based on a retrospective experience of 23 pediatric patients (age range: 8 to 21 years) with IBD flare (Crohn disease, n=12; ulcerative colitis: n=11); patients received rifaximin 400 to 1200 mg/day (10 to 30 mg/kg/day); improvements in diarrhea and abdominal pain were reported within the first 4 weeks of therapy for the majority of patients (~74%), and within a week in some cases; higher total daily doses (1200 mg/day vs 400 mg/day) were associated with better symptom control (Muniyappa 2009).

Small intestinal bacterial overgrowth (SIBO) (eg, irritable bowel syndrome [IBS], chronic abdominal pain): Limited data available; efficacy results variable: Oral: Children ≥3 years and Adolescents: 200 mg 3 times daily, dosing based on prospective study of 50 pediatric patients with IBS (age range: 3 to 15 years); results showed 7 days of therapy resulted in improved symptoms and a reduction in bacterial overgrowth based on lactulose breath test (LBT) results (Scarpellini 2013); however, a double-blind placebo-controlled trial in pediatric patients (n=75 including 49 who received rifaximin, age range: 8 to 18 years) with chronic abdominal pain showed very low efficacy in normalizing LBT (20% response rate) and treating SIBO compared to placebo at a higher dose of 550 mg 3 times daily for 7 days (Collins 2011).

Extemporaneously Prepared

A 20 mg/mL oral suspension may be made using tablets. Crush six 200 mg tablets and reduce to a fine powder. Add 30 mL of a 1:1 mixture of Ora-Sweet® and Ora-Plus® or a 1:1 mixture of Ora-Sweet® SF and Ora-Plus®; mix well while adding the vehicle in geometric proportions to almost 60 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 60 mL. Label "shake well". Stable 60 days at room temperature.

Cober MP, Johnson CE, Lee J, et al, "Stability of Extemporaneously Prepared Rifaximin Oral Suspensions," Am J Health Syst Pharm, 2010, 67(4):287-89.20133533

Administration

Oral: Administer with or without food.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Drug Interactions

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

CycloSPORINE (Systemic): May increase the serum concentration of RifAXIMin. Monitor therapy

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of RifAXIMin. Monitor therapy

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

Adverse Reactions

Frequency of adverse events generally higher following treatment for hepatic encephalopathy (HE). Percentages are presented for HE unless otherwise stated.

>10%:

Cardiovascular: Peripheral edema (15%)

Central nervous system: Dizziness (13%), fatigue (12%)

Hepatic: Ascites (11%)

Gastrointestinal: Nausea (14%; irritable bowel syndrome with diarrhea 2% to 3%)

2% to 10%:

Central nervous system: Headache (travelers' diarrhea 10%), depression (7%)

Dermatological: Pruritus (9%), skin rash (5%)

Gastrointestinal: Abdominal pain (>2% to 9%), pseudomembranous colitis (<5%; travelers' diarrhea or irritable bowel syndrome with diarrhea <2%)

Hematologic & oncologic: Anemia (8%)

Hepatic: Increased serum ALT (irritable bowel syndrome with diarrhea 2%)

Neuromuscular & skeletal: Muscle spasm (9%), arthralgia (6%), increased creatine phosphokinase (<5%; travelers' diarrhea or irritable bowel syndrome with diarrhea <2%)

Respiratory: Nasopharyngitis (7%), dyspnea (6%), epistaxis (>2% to 5%)

Miscellaneous: Fever (6%)

All indications: <2%, postmarketing, and/or case reports: Anaphylaxis, angioedema, Clostridioides (formerly Clostridium) difficile-associated diarrhea, exfoliative dermatitis, flushing, hypersensitivity reaction, urticaria

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity: Hypersensitivity reactions (eg, exfoliative dermatitis, rash, urticaria, flushing, angioneurotic edema, pruritus, anaphylaxis) have occurred; these events have occurred as early as within 15 minutes of drug administration.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including Clostridioides (formerly Clostridium) difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Diarrhea: Appropriate use: Avoid use in diarrhea with fever and/or blood in the stool and in the treatment of diarrhea due to pathogens other than Escherichia coli, including Campylobacter jejuni, ShigellaI spp., and Salmonella spp. (efficacy has not been established). Consider alternative therapy if symptoms persist or worsen after 24 to 48 hours of treatment.
• Hepatic impairment: Efficacy for prevention of encephalopathy has not been established in patients with a Model for End-Stage Liver Disease (MELD) score >25; use caution in patients with severe hepatic impairment (Child-Pugh class C).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).

Other warnings/precautions:

• Appropriate use: Not for treatment of systemic infections; <1% is absorbed orally.

Monitoring Parameters

Hypersensitivity reactions, temperature, blood in stool, change in symptoms; monitor changes in mental status in hepatic encephalopathy

Pregnancy

Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies. Due to the limited oral absorption of rifaximin in patients with normal hepatic function, exposure to the fetus is expected to be low.

Patient Education

What is this drug used for?

• It is used to treat diarrhea.
• It is used to prevent brain problems caused by very bad liver disease.
• It is used to treat irritable bowel syndrome.
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Stuffy nose
• Sore throat
• Muscle spasm
• Joint pain
• Headache
• Dizziness
• Abdominal pain
• Nausea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Swelling of arms or legs
• Abdominal edema
• Severe loss of strength and energy
• Shortness of breath
• Depression
• Clostridium difficile (C. diff)-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools.
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.