What are the indications and dosing regimens for Xifaxan (rifaximin)?

Xifaxan (Rifaximin): Indications and Dosing Regimens

Xifaxan (rifaximin) is FDA-approved for three main indications with specific dosing regimens: travelers' diarrhea (200 mg three times daily for 3 days), hepatic encephalopathy (550 mg twice daily), and irritable bowel syndrome with diarrhea (550 mg three times daily for 14 days). 1

FDA-Approved Indications and Dosing

1. Travelers' Diarrhea

• Dosage: 200 mg orally three times daily for 3 days 1
• Most effective for E. coli-predominant bacterial pathogens 2
• Less effective for dysenteric forms of bacterial diarrhea 2

2. Hepatic Encephalopathy (HE)

• Dosage: 550 mg orally twice daily 1
• Used as add-on therapy to lactulose or as monotherapy when lactulose is not tolerated 3
• Reduces risk of HE recurrence by 58% compared to placebo (hazard ratio 0.42) 3
• Number needed to treat: 4 patients for 6 months to prevent 1 episode of HE 4

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

• Dosage: 550 mg orally three times daily for 14 days 1
• Patients who experience symptom recurrence can be retreated up to two times with the same regimen 1
• Significantly more effective than placebo for IBS-D (40.7% vs 31.7% experienced adequate symptom relief) 4
• Particularly effective for improving stool consistency but has limited effect on abdominal pain 5

Mechanism of Action

Rifaximin is a poorly absorbed (<0.4%) rifamycin antibiotic that acts locally in the gastrointestinal tract with minimal systemic adverse effects 2, 6. Its mechanisms include:

• Direct antibacterial effects within the GI tract 4
• Reduction of bacterial virulence and pathogenicity 4
• Inhibition of bacterial translocation across the GI epithelial lining 4
• Modulation of gut-immune signaling 4
• Activation of the pregnane X receptor, reducing proinflammatory factors 4

Clinical Efficacy

For Hepatic Encephalopathy

• Combination of rifaximin and lactulose is superior to lactulose alone (recurrence rate: 22.1% vs 45.9%) 3
• Significantly fewer hospitalizations involving HE compared with placebo (13.6% vs 22.6%, p=0.01) 6

For IBS-D

• Significantly improves multiple concurrent IBS-D symptoms 7
• Effective for bloating and urgency symptoms (p≤0.03 vs placebo) 7
• Response can be seen as early as 1 week post-treatment 7
• The British Society of Gastroenterology recommends rifaximin as a second-line drug for IBS-D in secondary care 5

Safety Profile

• Excellent safety profile with adverse events comparable to placebo 2, 6
• Most common adverse events (10-15% of patients): ascites, dizziness, fatigue, peripheral edema 6
• In IBS trials: abdominal pain, diarrhea, bad taste, headache, upper respiratory tract infection (<10% of patients) 6
• Minimal risk of bacterial resistance 3, 2
• Low risk of Clostridium difficile-associated colitis 3

Administration

• Can be taken with or without food 1
• High fecal concentrations (>8000 μg/g after 3 days of oral therapy) 2

Important Clinical Considerations

• For IBS-D, monitor for 30% reduction from baseline in worst abdominal pain scores and improvement to Bristol Stool Form Scale score <5 3
• Use with caution in patients with severe hepatic impairment (Child-Pugh Class C) 3
• Monitor for potential drug interactions, particularly with warfarin 3
• Cost may impact long-term adherence, especially for chronic conditions like hepatic encephalopathy 3

Rifaximin's minimal systemic absorption contributes to its favorable safety profile while maintaining efficacy for its approved indications, making it a valuable option for treating localized gastrointestinal conditions.