What is Xifaxan (rifaximin) used for?

What is Xifaxan (Rifaximin) Used For?

Xifaxan (rifaximin) is FDA-approved for three primary indications: treating travelers' diarrhea caused by noninvasive E. coli, reducing the risk of recurrent hepatic encephalopathy in adults with cirrhosis, and treating irritable bowel syndrome with diarrhea (IBS-D) in adults. 1

FDA-Approved Indications

1. Travelers' Diarrhea (TD)

• Approved for treatment of TD caused by noninvasive strains of Escherichia coli in patients 12 years and older 1
• Rifaximin demonstrates comparable efficacy to fluoroquinolones for non-invasive TD caused by diarrheagenic E. coli 2
• Critical limitation: Rifaximin is NOT appropriate for dysentery (bloody diarrhea) or invasive pathogens such as Campylobacter, Salmonella, or Shigella, where it fails to achieve wellness in up to 50% of cases 2
• Rifaximin has the best safety profile compared to other first-line antibiotics for TD, with minimal systemic absorption (<1%) 2

2. Hepatic Encephalopathy (HE) Prevention

• FDA-approved for reducing the risk of recurrent overt hepatic encephalopathy in adults with advanced liver disease 1
• Dosing: 550 mg twice daily, used as an add-on to lactulose (not as monotherapy) 2, 3, 4
• Rifaximin reduces HE recurrence from 45.9% to 22.1% when added to lactulose (hazard ratio 0.42; 95% CI 0.28-0.64; p<0.001) 3
• Should be initiated after a second breakthrough episode of HE within 6 months of the first episode 3, 4
• Reduces HE-related hospitalizations by 50% (hazard ratio 0.50; 95% CI 0.29-0.87) 3
• Can be used safely for long-term continuous therapy (>24 months) with no increased risk of adverse events 3

Common pitfall: Rifaximin should NOT be used as monotherapy for HE—lactulose remains first-line treatment and rifaximin is added only after recurrent episodes 3, 4

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

• FDA-approved for treatment of IBS-D in adults at 550 mg three times daily for 14 days 2, 1
• Significantly improves abdominal pain (RR 0.87; 95% CI 0.80-0.95) and bloating (RR 0.86; 95% CI 0.70-0.93) compared to placebo 2
• Patients who respond initially and then relapse can be retreated up to 2 additional times with the same 14-day regimen 2
• Benefits persist for several weeks after completing the 2-week treatment course 2

Key Pharmacological Properties

• Nonabsorbable oral antibiotic with <1% systemic absorption, resulting in minimal systemic adverse effects 2, 5
• Broad-spectrum activity against gram-positive and gram-negative aerobic and anaerobic bacteria 2
• Excellent safety profile with adverse events similar to placebo in clinical trials 2, 5
• No increased risk of C. difficile infection with prolonged use 5

Important Contraindications and Limitations

For Travelers' Diarrhea:

• Do NOT use if diarrhea is complicated by fever or blood in stool 1
• Not appropriate for areas where invasive pathogens (Campylobacter, Salmonella, Shigella) are common (10-20% of TD cases) 2

For Hepatic Encephalopathy:

• Must be used in combination with lactulose—not as monotherapy 3, 4
• High cost ($1,500-2,000 per month) may be a barrier, though reduced hospitalizations may offset costs 3, 4

For IBS-D:

• Limited to 14-day treatment courses, with retreatment only after symptom recurrence 2