What are the recommended dosing regimens, side effects, and alternatives for rifaximin in adults for travel‑associated diarrhea, hepatic encephalopathy prevention, irritable bowel syndrome with diarrhea, and small‑intestinal bacterial overgrowth?

Rifaximin: Dosing, Side Effects, and Alternatives

Travel-Associated Diarrhea

For non-invasive travelers' diarrhea caused by diarrheagenic E. coli, use rifaximin 200 mg three times daily for 3 days, but avoid rifaximin entirely if dysentery (bloody diarrhea) or fever is present, as it fails in up to 50% of cases with invasive pathogens. 1, 2, 3

Dosing Regimen

• Treatment dose: 200 mg three times daily for 3 days 3
• Prophylaxis dose (if indicated): 200-1100 mg daily divided into 1-3 doses 1

When NOT to Use Rifaximin

• Do not use for dysentery (bloody diarrhea with fever), regardless of illness severity 1, 2
• Avoid in South and Southeast Asia where Campylobacter is common, as this organism is inherently resistant to rifaximin 1, 2
• Do not use for mild travelers' diarrhea - antibiotics are not recommended at all for mild cases 1, 2

Preferred Alternative

• Azithromycin is first-line for moderate-to-severe travelers' diarrhea and dysentery, with a single 1000 mg dose (or split over first day to reduce nausea) providing broader coverage including Campylobacter, Shigella, and Salmonella 1, 2
• Azithromycin has minimal side effects (3% nausea, <1% vomiting) and is effective regardless of geographic region 1

Side Effects

• Rifaximin has the best safety profile among first-line antibiotics for travelers' diarrhea, with adverse events similar to placebo 2, 3
• Minimal systemic absorption results in negligible systemic effects 4, 5

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Hepatic Encephalopathy Prevention

Use rifaximin 550 mg twice daily as add-on therapy to lactulose for preventing recurrent hepatic encephalopathy in cirrhotic patients, reducing recurrence risk by 58%. 3

Dosing Regimen

• Standard dose: 550 mg twice daily 3
• Always combine with lactulose unless lactulose is poorly tolerated 3

Treatment Algorithm

• First-line for acute hepatic encephalopathy: Lactulose alone 3
• For prevention of recurrence: Lactulose + rifaximin 550 mg twice daily 3
• Rifaximin monotherapy: Only when lactulose is poorly tolerated 3

Side Effects

• Excellent safety profile due to minimal systemic absorption 3, 4

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Irritable Bowel Syndrome with Diarrhea (IBS-D)

For IBS-D, use rifaximin 550 mg three times daily for 14 days, with the option to retreat up to 2 additional times if symptoms recur after initial response. 3

Dosing Regimen

• Treatment course: 550 mg three times daily for 14 days 3
• Retreatment: Up to 2 additional 14-day courses allowed for symptom recurrence 3

Efficacy Data

• Significantly improves FDA responder endpoint (RR 0.85; 95% CI 0.78-0.94) 3
• Reduces bloating (RR 0.86; 95% CI 0.70-0.93) 3
• Reduces abdominal pain (RR 0.87; 95% CI 0.80-0.95) 3
• Improves composite tri-symptom endpoint (abdominal pain, bloating, urgency) with effects maintained through ≥5 weeks post-treatment 6

Alternatives

• Loperamide for symptom control (not disease-modifying) 1
• Dietary modifications (low FODMAP diet) as adjunctive therapy
• Other antibiotics (metronidazole, levofloxacin) have more adverse events and less favorable profiles 7

Side Effects

• Negligible systemic absorption limits side effects 8
• More favorable adverse event profile than systemic antibiotics 7
• No clinically relevant bacterial resistance demonstrated 7, 5

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Small Intestinal Bacterial Overgrowth (SIBO)

For SIBO, rifaximin improves global symptoms in 33-92% of patients and eradicates SIBO in up to 84% of cases, with effects sustained up to 10 weeks post-treatment. 7

Dosing Regimen

• Typical dose: 550 mg three times daily for 14 days (extrapolated from IBS-D dosing) 3
• Alternative regimens of 400-550 mg 2-3 times daily have been studied 7

Efficacy

• SIBO eradication rates up to 84% 7
• Symptom improvement sustained up to 10 weeks after treatment 7

Alternatives

• Metronidazole: Higher adverse event rate compared to rifaximin 7
• Levofloxacin: Higher adverse event rate compared to rifaximin 7

Side Effects

• Lower adverse event rate than metronidazole or levofloxacin 7
• Minimal impact on intestinal microbiome 5
• No clinically relevant antibiotic resistance 7

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Key Clinical Pitfalls

Geographic Considerations

• Rifaximin fails in regions with high invasive pathogen prevalence (South/Southeast Asia, sub-Saharan Africa) 1, 2
• Always consider travel destination when selecting antibiotics for travelers' diarrhea 1

Pathogen-Specific Limitations

• Campylobacter, Salmonella, and Shigella are resistant to rifaximin 1, 2
• Any presentation with fever or bloody diarrhea requires azithromycin instead 1, 2

Drug Resistance Monitoring

• Long-term monitoring for resistant bacterial strains during chronic rifaximin use is lacking 8
• However, minimal systemic absorption limits development of extra-intestinal resistance 4