What is the purpose of Rifaximin?

Rifaximin: Clinical Purposes and Applications

Rifaximin is a nonabsorbable oral antibiotic FDA-approved for three primary indications: travelers' diarrhea caused by non-invasive E. coli (200 mg three times daily for 3 days), irritable bowel syndrome with diarrhea (550 mg three times daily for 14 days), and prevention of recurrent hepatic encephalopathy (550 mg twice daily). 1

Mechanism of Action

Rifaximin works by binding to the beta-subunit of bacterial DNA-dependent RNA polymerase, blocking transcription and inhibiting bacterial protein synthesis. 1 This semi-synthetic rifampin derivative has broad-spectrum activity against gram-positive and gram-negative aerobic and anaerobic bacteria, with minimal systemic absorption (<1% absorbed after oral administration). 1, 2

FDA-Approved Indications

Travelers' Diarrhea

• Dosing: 200 mg orally three times daily for 3 days 1
• Target pathogen: Non-invasive diarrheagenic Escherichia coli (enterotoxigenic and enteroaggregative strains) 1
• Efficacy: Significantly reduces median time to last unformed stool (32.5 hours vs 58.6 hours with placebo) and achieves clinical cure in 79% vs 60% with placebo 1
• Geographic limitations: Should NOT be used in areas where invasive pathogens are common (Southeast Asia, South Asia) due to limited efficacy against Campylobacter and invasive organisms 3, 4, 5

Irritable Bowel Syndrome with Diarrhea (IBS-D)

• Dosing: 550 mg orally three times daily for 14 days 3, 1
• Retreatment: Patients with initial response who develop recurrent symptoms can be retreated up to 2 times with the same regimen 3
• Efficacy outcomes:
  • FDA responder endpoint: RR 0.85 (95% CI 0.78-0.94) vs placebo 3
  • Bloating relief: RR 0.86 (95% CI 0.70-0.93) 3
  • Abdominal pain relief: RR 0.87 (95% CI 0.80-0.95) 3

Hepatic Encephalopathy Prevention

• Dosing: 550 mg orally twice daily 4
• Use: Add-on therapy to lactulose for prevention of recurrent hepatic encephalopathy in cirrhotic patients 4
• Efficacy: Reduces risk of recurrent hepatic encephalopathy by 58% when added to lactulose (22% breakthrough episodes vs 46% with placebo, P<0.001) 4, 6
• Monotherapy: Should only be used alone when lactulose is poorly tolerated 4

Prophylactic Use Considerations

Travelers' Diarrhea Prophylaxis

• Recommendation: Consider prophylaxis ONLY in high-risk groups (underlying health conditions or performance-critical occupation/itinerary) 3, 5
• Dosing for prophylaxis: 200-1100 mg daily divided into 1-3 doses 3
• Geographic efficacy: Only moderate protective effectiveness in South/Southeast Asia where Campylobacter is common 3, 5
• Strong recommendation against: Fluoroquinolones should NOT be used for TD prophylaxis due to emerging resistance and potential harm to peripheral/central nervous system, tendons, muscles, and joints 3

Safety Profile

Rifaximin has an extremely favorable safety profile due to minimal systemic absorption. 3, 4 Common adverse events (occurring in <15% of patients) include ascites, dizziness, fatigue, peripheral edema (in HE patients), and abdominal pain, diarrhea, headache (in IBS patients). 6

Important Drug Interactions

• Oral contraceptives: The 3-day regimen (200 mg three times daily) does not alter ethinyl estradiol or norgestimate pharmacokinetics. 1 However, the 7-day regimen (550 mg three times daily) reduces mean Cmax of ethinyl estradiol by 25% and norgestimate by 13%, though clinical relevance is unknown. 1
• CYP3A4 substrates: No significant effect on intestinal or hepatic CYP3A4 activity 1

Critical Contraindications and Precautions

• Do NOT use for dysentery or febrile invasive diarrheal disease regardless of severity 4
• Do NOT use empirically in patients with inflammatory bowel disease traveling to developing countries—prescribe fluoroquinolones (ciprofloxacin 500 mg twice daily) or azithromycin instead 5
• Geographic restriction: In Southeast Asia, prescribe azithromycin instead due to higher rates of invasive pathogens 5

Resistance Profile

Resistance occurs primarily through mutations in the rpoB gene, which alters the binding site on DNA-dependent RNA polymerase. 1 Importantly, cross-resistance between rifaximin and other antimicrobial classes has not been observed, and selection of resistant mutants is unusual compared to related rifampin. 1, 7