What are the indications for Xifaxin (Rifaximin)?

Rifaximin (Xifaxan) Indications

Rifaximin is FDA-approved for three primary indications: treatment of travelers' diarrhea caused by noninvasive strains of E. coli, reduction in risk of overt hepatic encephalopathy recurrence, and treatment of irritable bowel syndrome with diarrhea (IBS-D). 1

FDA-Approved Indications

1. Travelers' Diarrhea (TD)

• Dosage: 200 mg three times daily for 3 days 1
• Patient population: Adults and pediatric patients 12 years and older
• Specific pathogen: Only for noninvasive strains of Escherichia coli
• Important limitations:
  • Not for use in diarrhea complicated by fever or blood in stool
  • Not effective for diarrhea caused by pathogens other than E. coli 1
  • Should be avoided in areas where invasive pathogens like Campylobacter, Salmonella, and Shigella are common 2
  • Ineffective in South and Southeast Asia where Campylobacteriosis is more prevalent 3

2. Hepatic Encephalopathy (HE)

• Dosage: 550 mg twice daily (continuous therapy) 1
• Patient population: Adults
• Clinical use: Reduces risk of overt HE recurrence by 58% compared to placebo 2
• Recommended approach: Typically used as add-on therapy when lactulose alone fails in preventing recurrent HE 2

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

• Dosage: 550 mg three times daily for 14 days 1
• Patient population: Adults
• Retreatment: Patients who experience recurrence can be retreated up to 2 times with the same regimen 1
• Efficacy: Moderate efficacy for global symptoms, though effect on abdominal pain may be limited 3
• Position in treatment algorithm: Recommended as a second-line drug for IBS-D in secondary care 3

Clinical Considerations

For Travelers' Diarrhea:

• Rifaximin has an excellent safety profile compared to other antibiotics for TD 2
• Rifaximin can be used as monotherapy or combined with loperamide for faster symptomatic relief 2
• Patients should discontinue rifaximin and consider alternative antibiotics if symptoms worsen or persist beyond 24-48 hours 1

For Hepatic Encephalopathy:

• Most effective when used as an adjunct to lactulose after ≥1 additional episodes of overt HE within 6 months 2
• Can be used alone in patients who cannot tolerate lactulose 2
• Monitor for drug interactions, particularly with warfarin 2, 1

For IBS-D:

• Efficacy demonstrated in multiple RCTs with moderate certainty of evidence 3
• In retreatment studies, rifaximin showed durable response and prevention of symptom recurrence compared to placebo 3
• Adverse event profile similar to placebo in clinical trials 3

Safety Profile

• Minimal systemic absorption (<0.4%) 4
• Most common adverse reactions:
  • TD: Headache (≥2%)
  • HE: Peripheral edema, nausea, dizziness, fatigue, and ascites (≥10%)
  • IBS-D: ALT increased, nausea (≥2%) 1
• Use with caution in patients with severe hepatic impairment (Child-Pugh Class C) 1
• Monitor INR and prothrombin time when used with warfarin 1

Pitfalls and Caveats

• Rifaximin is ineffective against inflammatory or invasive enteropathogens 4
• May cause Clostridium difficile-associated diarrhea; evaluate if diarrhea occurs after therapy or does not improve/worsens during therapy 1
• Exercise caution when using concomitantly with P-glycoprotein inhibitors (e.g., cyclosporine) 1
• Not recommended during pregnancy as it may cause fetal harm 1

Rifaximin's unique pharmacokinetic properties—bile solubility making it active in the small bowel and low water solubility limiting activity in the colon—contribute to its targeted antimicrobial effects with minimal systemic absorption 5.