How often can Xifaxin (Rifaximin) be repeated?

Xifaxin (Rifaximin) Retreatment Frequency

For IBS-D, patients who initially respond to rifaximin 550 mg three times daily for 14 days can be retreated up to 2 times with the same dosage regimen when symptoms recur. 1, 2

FDA-Approved Retreatment Protocol

The FDA label explicitly states that patients experiencing recurrence of IBS-D symptoms can be retreated up to 2 times with rifaximin 550 mg three times daily for 14 days. 2 This means:

• Initial treatment course: 550 mg three times daily × 14 days 1
• First retreatment: Same regimen when symptoms recur 1
• Second retreatment: Same regimen if symptoms recur again 1
• Maximum total: 3 treatment courses (1 initial + 2 retreatments) 2

When to Initiate Retreatment

Retreatment should be initiated when patients experience symptom relapse after an initial response. 1 The pivotal trial defined relapse as:

• Loss of treatment response in either abdominal pain (failure to maintain ≥30% decrease from baseline) OR stool consistency (failure to maintain ≥50% reduction in loose/watery stool days) for 3 weeks during a consecutive 4-week period 1
• Median time to recurrence in responders was 10 weeks (range 6-24 weeks) 2

Evidence Supporting Retreatment

The 2022 AGA guidelines provide a conditional recommendation with moderate certainty evidence for rifaximin retreatment in IBS-D patients who initially respond. 1 Key findings from the phase 3 retreatment trial:

• Prevention of recurrence: Rifaximin reduced symptom recurrence compared to placebo (RR 0.93; 95% CI 0.88-0.99) 1
• Sustained symptom relief: More patients maintained durable response with rifaximin (RR 0.94; 95% CI 0.88-1.00) 1
• Safety profile: Drug-related adverse events were comparable to placebo (RR 0.70; 95% CI 0.25-2.01) 1

Critical Limitations and Safety Considerations

The AGA explicitly recommends against exceeding 2 retreatment courses, as safety and efficacy data beyond this are limited. 3 Important caveats include:

• No clinical trial data exist for more than 2 retreatment courses 1
• The retreatment trial followed patients for only 51 weeks total 1
• One case of C. difficile colitis occurred in the retreatment trial (though the patient had prior C. difficile history and recent cefdinir use) 1

Dosing for Other Indications

For context, rifaximin dosing differs substantially by indication:

• Travelers' diarrhea: 200 mg three times daily × 3 days (not repeatable per protocol) 2, 4
• Hepatic encephalopathy: 550 mg twice daily continuously (chronic use) 2
• IBS-D: 550 mg three times daily × 14 days (repeatable up to 2 times) 2

Common Pitfalls to Avoid

• Do not use rifaximin for invasive pathogens (Shigella, Campylobacter, Salmonella) where azithromycin is preferred 3
• Do not exceed 2 retreatment courses without compelling clinical justification, as this exceeds FDA-approved and evidence-based use 3, 2
• Do not use for diarrhea complicated by fever or bloody stools, as rifaximin is ineffective in these scenarios 2
• Monitor for treatment failure: If diarrhea persists >24-48 hours or worsens, discontinue and consider alternative antibiotics 2