What are the uses and dosages of Xifaxan (rifaximin)?

Xifaxan (Rifaximin): Uses and Dosages

FDA-Approved Indications and Dosing

Xifaxan (rifaximin) has three FDA-approved indications with specific dosing regimens that should be followed precisely for optimal outcomes. 1

1. Travelers' Diarrhea

• Dosage: 200 mg orally three times daily for 3 days 1
• Population: Adults and pediatric patients ≥12 years of age 1
• Indication: Treatment of travelers' diarrhea caused by noninvasive strains of Escherichia coli 1

Critical limitations and contraindications:

• Do NOT use if diarrhea is complicated by fever or blood in stool 1
• Ineffective against Campylobacter jejuni (common in Southeast Asia) 1
• Unproven efficacy against Shigella spp. and Salmonella spp. 1
• Discontinue if symptoms worsen or persist beyond 24-48 hours 1
• For Southeast Asia travel, prescribe azithromycin instead due to higher rates of invasive pathogens 2

2. Hepatic Encephalopathy

• Dosage: 550 mg orally twice daily 1
• Population: Adults for reduction in risk of overt hepatic encephalopathy recurrence 1
• Important considerations:
  • 91% of trial patients used lactulose concomitantly; rifaximin should NOT be used as monotherapy 1, 3
  • Not studied in patients with MELD scores >25 1
  • Exercise caution in Child-Pugh Class C hepatic impairment due to increased systemic exposure 1
  • Alternative dosing of 400 mg three times daily (maximum 1,200 mg/day) used in some clinical settings 3

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

• Dosage: 550 mg orally three times daily for 14 days 1
• Population: Adults only 1
• Retreatment: Patients with symptom recurrence can be retreated up to two times using the same dosage regimen 1

Evidence supporting IBS-D use:

• Rifaximin is an efficacious second-line drug for IBS-D in secondary care, though its effect on abdominal pain is limited 4
• Significantly improves the FDA responder endpoint (RR 0.85,95% CI 0.78-0.94) and provides relief of bloating 2
• The British Society of Gastroenterology (2021) and American Gastroenterological Association (2022) both recommend rifaximin as a second-line agent for IBS-D 4
• Headache is the most common adverse event, but side effects are no more common than placebo 4

Administration

• Can be taken with or without food 1

Off-Label and Prophylactic Uses

Travelers' Diarrhea Prophylaxis

• Consider prophylaxis ONLY in high-risk groups: travelers with underlying health conditions or performance-critical occupations/itineraries 2
• Dosing for prophylaxis: 200-1100 mg daily divided into 1-3 doses confers strong protection 4
• Geographic limitations: Only moderate effectiveness in South/Southeast Asia where Campylobacter is common 4, 2
• Bismuth subsalicylate is the second option for prophylaxis 2
• Strong recommendation AGAINST fluoroquinolones for prophylaxis due to emerging resistance and potential for serious adverse events affecting peripheral/central nervous system, tendons, muscles, and joints 4

Recurrent Clostridioides difficile Infection (Pediatric)

• For second or subsequent recurrence in children: vancomycin for 10 days followed by rifaximin 400 mg three times daily for 20 days 3

Critical Safety Warnings

Contraindications

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

Clostridioides difficile-Associated Diarrhea (CDAD)

• CDAD has been reported with rifaximin use and may range from mild diarrhea to fatal colitis 1
• Can occur over two months after antibiotic administration 1
• If CDAD is suspected, discontinue rifaximin and initiate appropriate management 1

Special Populations to Avoid

• Do NOT use empirically in patients with inflammatory bowel disease for travelers' diarrhea—no evidence supports this practice 2
• For IBD patients traveling to developing countries, prescribe fluoroquinolones (ciprofloxacin 500 mg twice daily) or azithromycin instead 2

Key Clinical Pearls

Common pitfalls to avoid:

• Using rifaximin for febrile or bloody diarrhea (ineffective and delays appropriate treatment) 1
• Prescribing for travel to Southeast Asia without considering regional pathogen patterns 4, 2
• Using as monotherapy for hepatic encephalopathy without lactulose 3, 1
• Prescribing prophylactically for low-risk travelers (increases antimicrobial resistance) 4, 2, 1