Introduction
Xifaxan (rifaximin) is a semisynthetic, nonsystemic antibiotic derived from rifamycin. It is structurally related to rifampin but exhibits minimal systemic absorption, making it particularly useful for treating gastrointestinal conditions with localized antibiotic effects. Approved by the FDA in 2004, Xifaxan has become an important therapeutic option for several gastrointestinal disorders.
Mechanism of Action
Rifaximin binds to the beta-subunit of bacterial DNA-dependent RNA polymerase, inhibiting bacterial RNA synthesis. Its action is primarily bactericidal against susceptible organisms. Unlike systemic rifamycins, rifaximin's minimal systemic absorption (<0.4%) allows it to achieve high concentrations in the gastrointestinal lumen while minimizing systemic exposure and associated side effects.
Indications
- Travelers' Diarrhea: Caused by noninvasive strains of Escherichia coli in patients ≥12 years
- Hepatic Encephalopathy: Reduction in risk of overt hepatic encephalopathy recurrence in adults
- Irritable Bowel Syndrome with Diarrhea (IBS-D): For adults to relieve symptoms
- Small Intestinal Bacterial Overgrowth (SIBO): Off-label use based on clinical evidence
Dosage and Administration
Travelers' Diarrhea: 200 mg orally three times daily for 3 days Hepatic Encephalopathy: 550 mg orally twice daily IBS-D: 550 mg orally three times daily for 14 days; may be repeated if symptoms recur Special Populations:- Renal impairment: No dosage adjustment required
- Hepatic impairment: No dosage adjustment required
- Pediatrics: Safety and effectiveness not established for travelers' diarrhea in children <12 years
- Geriatrics: No specific dosage adjustment recommended
Pharmacokinetics
- Absorption: <0.4% systemic bioavailability; primarily acts locally in GI tract
- Distribution: Minimal systemic distribution; high concentrations in feces
- Metabolism: Undergoes minimal metabolism; primarily eliminated unchanged
- Elimination: Primarily excreted in feces (97%); renal excretion <1%
- Half-life: Approximately 6 hours
Contraindications
- Hypersensitivity to rifaximin, other rifamycin antimicrobial agents, or any component of the formulation
- Patients with known serious hypersensitivity reactions to rifaximin
Warnings and Precautions
- Clostridium difficile-associated diarrhea: May occur with antibiotic use; consider diagnosis in patients who develop diarrhea after antibiotic use
- Superinfection: May result in bacterial or fungal overgrowth
- Travelers' Diarrhea: Not effective in patients with diarrhea complicated by fever or blood in stool or diarrhea due to pathogens other than E. coli
- Hepatic encephalopathy: Not for treatment of overt hepatic encephalopathy; use as maintenance therapy to reduce recurrence
- Drug-resistant bacteria: Prolonged use may promote development of drug-resistant bacteria
Drug Interactions
- P-glycoprotein (P-gp) substrates: Rifaximin may increase exposure of P-gp substrates (e.g., digoxin, cyclosporine) due to P-gp induction
- Warfarin: Monitor INR as rifaximin may potentially affect vitamin K-producing gut flora
- Oral contraceptives: Theoretical potential for reduced efficacy due to effects on gut flora; recommend backup contraception
Adverse Effects
Common (≥2%):- Nausea (10%)
- Flatulence (6%)
- Headache (6%)
- Abdominal pain (5%)
- Constipation (4%)
- Pyrexia (3%)
- Vomiting (3%)
- Dizziness (3%)
- Fatigue (2%)
- Peripheral edema (2%)
- Clostridium difficile-associated diarrhea
- Severe hypersensitivity reactions (angioedema, anaphylaxis)
- Stevens-Johnson syndrome (rare)
Monitoring Parameters
- For hepatic encephalopathy: Mental status, asterixis, ammonia levels (though clinical correlation is more important than ammonia levels alone)
- For travelers' diarrhea: Resolution of symptoms, signs of dehydration
- For all patients: Signs of superinfection, C. difficile-associated diarrhea
- Liver function tests: In patients with pre-existing liver disease
- Renal function: Though minimal systemic absorption, consider in severely ill patients
Patient Education
- Take exactly as prescribed; complete full course even if symptoms improve
- May be taken with or without food
- Report any worsening diarrhea, bloody stools, or abdominal pain
- For travelers' diarrhea: Maintain adequate hydration
- For hepatic encephalopathy: This is maintenance therapy, not for acute episodes
- Inform healthcare provider of all medications being taken
- Report any signs of allergic reaction (rash, swelling, difficulty breathing)
- Store at room temperature (20-25°C/68-77°F)
References
1. FDA Prescribing Information: Xifaxan (rifaximin) tablets. Revised 2022. 2. DuPont HL. Rifaximin: a nonsystemic rifamycin antibiotic for gastrointestinal diseases. Chemotherapy. 2005;51 Suppl 1:36-66. 3. Bass NM, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362(12):1071-1081. 4. Pimentel M, et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011;364(1):22-32. 5. Scarpignato C, et al. Rifaximin rediscovers its second youth in the management of irritable bowel syndrome. Minerva Gastroenterol Dietol. 2018;64(2):126-146. 6. American College of Gastroenterology guidelines on the management of irritable bowel syndrome. Am J Gastroenterol. 2021;116(1):17-44. 7. Hepatic Encephalopathy: 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.
This monograph is for educational purposes only and does not replace professional medical advice. Always consult with a healthcare provider for specific medical guidance.