When is Rifaximin (rifamycin derivative antibiotic) used?

When to Use Rifaximin

Rifaximin is indicated for three FDA-approved conditions: travelers' diarrhea caused by non-invasive E. coli, prevention of recurrent hepatic encephalopathy, and irritable bowel syndrome with diarrhea (IBS-D). 1

FDA-Approved Indications

Travelers' Diarrhea

• Use rifaximin 200 mg three times daily for 3 days for travelers' diarrhea caused by non-invasive strains of E. coli in patients ≥12 years of age. 1
• Rifaximin is appropriate for all regions except Southeast Asia, where azithromycin should be prescribed instead due to higher rates of invasive pathogens. 2
• Do NOT use rifaximin if the patient has fever, bloody diarrhea (dysentery), or suspected invasive pathogens—these require azithromycin or fluoroquinolones instead. 2, 3, 1
• If rifaximin is given as first-line therapy, always provide backup azithromycin in case dysentery or febrile diarrhea develops. 2
• Rifaximin has treatment failure rates up to 50% in areas where invasive pathogens like Campylobacter are common (South/Southeast Asia). 3

Hepatic Encephalopathy

• Use rifaximin 550 mg twice daily to reduce the risk of recurrent overt hepatic encephalopathy in adults. 1, 4
• Rifaximin should be added to lactulose therapy, not used as monotherapy—combination therapy provides superior outcomes. 3, 4
• Use rifaximin alone only when lactulose is poorly tolerated. 3
• Rifaximin reduces the risk of recurrent hepatic encephalopathy by 58% when added to lactulose. 3
• For covert hepatic encephalopathy, rifaximin can improve quality of life and reduce progression to overt encephalopathy. 3

Irritable Bowel Syndrome with Diarrhea (IBS-D)

• Use rifaximin 550 mg three times daily for 14 days in adults with IBS-D. 3, 4, 1
• Patients who respond initially but have symptom recurrence can be retreated up to 2 additional times using the same 14-day regimen. 3, 4
• Rifaximin significantly improves the FDA responder endpoint for IBS-D (RR 0.85,95% CI 0.78-0.94) and provides relief of bloating and abdominal pain. 3

Off-Label and Prophylactic Uses

Travelers' Diarrhea Prophylaxis

• Consider rifaximin prophylaxis only in high-risk groups (underlying health conditions or performance-critical occupation/itinerary). 2
• Rifaximin is the first choice for prophylaxis, with bismuth subsalicylate as second option. 2
• If using rifaximin for prophylaxis, provide azithromycin for standby breakthrough therapy. 2
• Prophylactic effectiveness is only moderate in South/Southeast Asia where Campylobacter is common. 3

NOT Recommended

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

Key Clinical Advantages

• Rifaximin has minimal systemic absorption (<0.4%), resulting in an excellent safety profile with the fewest adverse effects compared to other antibiotics for travelers' diarrhea. 3, 5
• Negligible drug interactions and minimal impact on intestinal microbiome compared to systemically absorbed antibiotics. 5
• No dose adjustment needed for renal or hepatic impairment due to minimal absorption. 5

Important Caveats

• Rifaximin requires oral administration—it is not appropriate for patients who cannot take oral medications. 4
• The drug does not significantly affect CYP3A4 activity, so drug interactions are minimal. 1
• Oral contraceptive efficacy may be slightly reduced (Cmax decreased by 13-25%), though clinical significance is unknown. 1