What are the FDA‑approved indications, dosing regimens, and safety considerations for Xifaxan (rifaximin)?

Xifaxan (Rifaximin): FDA-Approved Indications, Dosing, and Safety

FDA-Approved Indications

Xifaxan (rifaximin) has three FDA-approved indications: travelers' diarrhea caused by noninvasive E. coli, reduction of hepatic encephalopathy recurrence risk, and irritable bowel syndrome with diarrhea (IBS-D). 1

1. Travelers' Diarrhea

• Approved for treatment of travelers' diarrhea caused by noninvasive strains of Escherichia coli in adults and pediatric patients ≥12 years of age 1
• Dosing: 200 mg orally three times daily for 3 days 1
• Rifaximin demonstrates superior efficacy to placebo and comparable efficacy to fluoroquinolones for uncomplicated travelers' diarrhea 2
• Critical limitation: Should NOT be used if diarrhea is complicated by fever or bloody stools, or when invasive pathogens (Campylobacter, Shigella, Salmonella) are suspected 1, 2
• Rifaximin is ineffective against Campylobacter jejuni and has only moderate protective effectiveness in South and Southeast Asia where Campylobacter is more common 2, 1
• Discontinue if diarrhea worsens or persists beyond 24-48 hours and switch to alternative antibiotic therapy 1

2. Hepatic Encephalopathy

• Approved for reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults 1
• Dosing: 550 mg orally twice daily 1
• Should be used as add-on therapy to lactulose (91% of trial patients used concomitant lactulose), not as monotherapy 1, 3
• Reduces risk of recurrent hepatic encephalopathy by 58% when added to lactulose 3, 4
• Caution in severe hepatic impairment (Child-Pugh Class C): increased systemic exposure occurs; trials limited to MELD scores <25, with only 8.6% having MELD >19 1

3. Irritable Bowel Syndrome with Diarrhea (IBS-D)

• Approved for treatment of IBS-D in adults 1
• Dosing: 550 mg orally three times daily for 14 days 1, 2
• Patients with symptom recurrence can be retreated up to two times with the same dosage regimen 1, 2
• Demonstrates significant improvement in FDA responder endpoint (RR 0.85; 95% CI 0.78-0.94) 2
• Improves bloating (RR 0.86; 95% CI 0.70-0.93) and abdominal pain (RR 0.87; 95% CI 0.80-0.95) 2
• Response assessed during 4 weeks immediately following treatment completion 2

Administration

• Can be taken with or without food 1

Safety Profile and Contraindications

Contraindications

• Hypersensitivity to rifaximin, any rifamycin antimicrobial agents, or any component in Xifaxan 1
• Hypersensitivity reactions include exfoliative dermatitis, angioneurotic edema, and anaphylaxis 1

Excellent Safety Profile

• Minimal systemic absorption (<0.4% bioavailability), resulting in negligible systemic adverse events 2, 3, 4
• Tolerability profile similar to placebo 2
• No increased rates of C. difficile infection observed with prolonged use 3
• Minimal drug-drug interactions due to negligible systemic absorption 2

Important Warnings

• Clostridium difficile-associated diarrhea (CDAD) can occur with rifaximin use, ranging from mild diarrhea to fatal colitis 1
• CDAD must be considered in all patients presenting with diarrhea following rifaximin use; has been reported up to 2 months after antibiotic administration 1
• If CDAD suspected or confirmed, discontinue rifaximin and institute appropriate management (fluid/electrolyte management, C. difficile-directed therapy, surgical evaluation as indicated) 1

Development of Drug-Resistant Bacteria

• Prescribing rifaximin without proven or strongly suspected bacterial infection increases risk of drug-resistant bacteria development 1
• Minimal potential for bacterial resistance development compared to systemic antibiotics 2

Critical Clinical Pitfalls

When NOT to Use Rifaximin

• Febrile diarrhea or bloody stools (dysentery): Use azithromycin instead as first-line therapy 2
• Geographic regions with high rates of invasive pathogens (South/Southeast Asia, India, sub-Saharan Africa): Clinical failure rates up to 50% with invasive pathogens 2, 4, 5
• Suspected Campylobacter, Shigella, or Salmonella infections: Rifaximin is ineffective or unproven against these pathogens 1, 2
• Severe hepatic impairment (Child-Pugh Class C): Exercise caution due to increased systemic exposure 1

Prophylaxis Considerations

• Rifaximin 200-1100 mg daily (divided into 1-3 doses) provides strong protection against travelers' diarrhea 2
• Prophylaxis should be reserved for high-risk travelers (history of post-infectious complications like reactive arthritis, or serious chronic illness predisposing to TD complications) 2
• Moderate effectiveness only in regions with high Campylobacter prevalence 2