What is the recommended dosing for Xifaxin (Rifaximin)?

Xifaxin (Rifaximin) Dosing

The recommended dose of Xifaxin varies by indication: 200 mg three times daily for 3 days for travelers' diarrhea, 550 mg twice daily for hepatic encephalopathy, and 550 mg three times daily for 14 days for IBS-D, with retreatment allowed up to 2 times for symptom recurrence. 1

Dosing by Clinical Indication

Travelers' Diarrhea (TD)

• 200 mg orally three times daily for 3 days is the FDA-approved regimen for TD caused by noninvasive Escherichia coli in patients ≥12 years old 1
• This dosing provides 72% protection against TD and 77% protection against antibiotic-treated TD 2
• Rifaximin can be taken with or without food 1

Critical limitation: Rifaximin should NOT be used if diarrhea is complicated by fever, blood in stool, or when invasive pathogens (Campylobacter jejuni, Shigella, Salmonella) are suspected 1, 3

• Rifaximin demonstrates documented treatment failures in up to 50% of cases with invasive pathogens 3
• For invasive/febrile diarrhea, azithromycin is the preferred agent 3, 4

Hepatic Encephalopathy (HE)

• 550 mg orally twice daily for long-term reduction in risk of overt HE recurrence 1, 3
• 91% of patients in clinical trials used lactulose concomitantly 1
• This regimen reduces breakthrough HE episodes by 58% (hazard ratio 0.42) and HE-related hospitalizations by 50% (hazard ratio 0.50) compared to placebo 5
• Long-term safety demonstrated for up to 24 months with median exposure of 427 days 5

Important caveat: Exercise caution in severe hepatic impairment (Child-Pugh Class C), as systemic exposure increases 21-fold compared to healthy volunteers 1

• Clinical trials were limited to patients with MELD scores <25; only 8.6% had MELD scores >19 1

Irritable Bowel Syndrome with Diarrhea (IBS-D)

• 550 mg orally three times daily for 14 days is the FDA-approved regimen 1, 3
• Patients with symptom recurrence can be retreated up to 2 times with the same dosage regimen 1, 3
• The AGA recommends against exceeding 2 retreatment courses due to limited safety data beyond this 6
• Rifaximin provides 40.8% symptom improvement versus 31.7% with placebo (P < 0.001) 7

Prophylaxis Dosing (Not FDA-Approved but Evidence-Based)

For travelers at high risk of TD-related complications (e.g., history of post-infectious reactive arthritis, serious chronic illness):

• 200-1100 mg daily divided into 1-3 doses provides strong protection against TD 3
• Most studies used 200 mg three times daily for prevention 2
• Prophylaxis is NOT routinely recommended for average travelers due to concerns about antimicrobial resistance 3

Strong recommendation against fluoroquinolones for TD prophylaxis due to emerging resistance (70-80% in Campylobacter from Nepal/Thailand) and potential for serious adverse effects affecting peripheral/central nervous system, tendons, muscles, and joints 3

Safety Profile and Key Considerations

• Rifaximin has minimal systemic absorption (<0.4%), resulting in an extremely favorable safety profile comparable to placebo 1, 8
• No increase in Clostridium difficile infections or development of bacterial antibiotic resistance with long-term use 5
• Minimal changes in intestinal coliform flora during therapy 2
• Most common adverse events (10-15%): ascites, dizziness, fatigue, peripheral edema (HE trials); abdominal pain, diarrhea, headache (<10% in IBS trials) 7

Clinical Decision Algorithm

For acute diarrhea:

1. Assess for fever, blood in stool, or severe systemic symptoms

   • If present → Use azithromycin, NOT rifaximin 3, 4
   • If absent and noninvasive pathogen suspected → Rifaximin 200 mg TID × 3 days 1

2. Geographic considerations:

   • South/Southeast Asia (high Campylobacter prevalence) → Rifaximin has only moderate effectiveness; consider azithromycin 3
   • Other regions with predominantly ETEC → Rifaximin highly effective 3, 9

For chronic conditions:

• HE maintenance: 550 mg BID indefinitely 1
• IBS-D: 550 mg TID × 14 days, retreatable up to 2 times for recurrence 1, 3

Contraindications: Hypersensitivity to rifaximin or any rifamycin antimicrobial agent 1