When is rifaximin (antibiotic) indicated for use?

When to Use Rifaximin

Rifaximin is FDA-approved for three specific indications: travelers' diarrhea caused by noninvasive E. coli in patients ≥12 years, reduction in risk of overt hepatic encephalopathy recurrence in adults, and treatment of irritable bowel syndrome with diarrhea in adults. 1

Primary Indications

Hepatic Encephalopathy (HE)

Start rifaximin 550 mg twice daily as secondary prophylaxis following more than one episode of overt HE within 6 months of the first episode, always in combination with lactulose. 2, 3

The treatment algorithm for HE follows this sequence:

• First-line acute treatment: Lactulose 20-30g (30-45 mL) orally 3-4 times daily, titrated to achieve 2-3 soft stools per day 2, 3, 4
• After first resolved episode: Continue lactulose alone as secondary prophylaxis 2, 3
• After second breakthrough episode: Add rifaximin 550 mg twice daily to ongoing lactulose therapy 2, 3, 5
• Long-term maintenance: Continue rifaximin indefinitely—do not discontinue after initial improvement as recurrence rates are high without continuous prophylaxis 4, 6

The evidence supporting this approach is robust. In the landmark trial, rifaximin plus lactulose reduced HE recurrence from 45.9% to 22.1% (hazard ratio 0.42; 95% CI 0.28-0.64; p<0.001), with 91% of patients on concurrent lactulose therapy. 2, 3 This represents a number needed to treat of 4 for preventing recurrent HE. 2

Critical pitfall: Do not use rifaximin as monotherapy for acute overt HE episodes—lactulose remains the cornerstone of acute treatment. 4 Rifaximin monotherapy may only be considered when lactulose is poorly tolerated, though this is based on expert opinion rather than robust evidence. 2, 4

Pre-TIPS Prophylaxis

Consider rifaximin 600 mg twice daily starting 14 days before non-urgent TIPS placement in patients with previous episodes of overt HE, continuing for approximately 6 months post-procedure. 5 This significantly reduces post-TIPS HE incidence from 53% to 34%. 5

Irritable Bowel Syndrome with Diarrhea (IBS-D)

Start rifaximin 550 mg three times daily for 14 days in patients meeting Rome III criteria for IBS-D with baseline abdominal pain scores ≥3 and loose stools (Bristol Stool Form Scale type 6 or 7) at least 2 days per week. 5, 1 Patients can be retreated up to 2 times with the same dosage regimen if symptoms recur after initial response. 5, 1

Travelers' Diarrhea

Use rifaximin 200 mg three times daily for 3 days in patients ≥12 years with travelers' diarrhea caused by noninvasive E. coli. 1

Do not use in patients with diarrhea complicated by fever or blood in stool, or diarrhea due to pathogens other than E. coli. 1 If diarrhea symptoms worsen or persist for more than 24-48 hours, discontinue rifaximin and consider alternative antibiotics. 1

Safety and Duration Considerations

Rifaximin can be used safely for long-term continuous therapy (>24 months) with no increased risk of adverse events, bacterial resistance, or C. difficile infection. 4, 6 In the all-rifaximin population with median exposure of 427 days (range 2-1427 days), the safety profile remained comparable to the original 6-month trial. 6

Common adverse events in HE patients (10-15%): peripheral edema, nausea, dizziness, fatigue, and ascites. 1 These rates are similar to placebo. 2

Use with caution in patients with severe hepatic impairment (Child-Pugh Class C) and when co-administering P-glycoprotein inhibitors like cyclosporine. 1

Cost-Benefit Analysis

The high cost of rifaximin (approximately $1,500-2,000 per month) may be a significant barrier to routine use. 2 However, rifaximin reduces HE-related hospitalizations (hazard ratio 0.50; 95% CI 0.29-0.87), which may offset costs through reduced hospital admissions. 2, 7

Transplant Considerations

A first episode of overt HE should prompt referral to a transplant center for evaluation. 2 Patients with recurrent or persistent HE despite adequate medical treatment (lactulose plus rifaximin) should be considered for liver transplantation. 2

Dosing Summary Table

Indication	Dose	Duration	Key Points
HE Prevention	550 mg twice daily	Indefinite	Add after 2nd breakthrough episode; always with lactulose [2,3]
Pre-TIPS Prophylaxis	600 mg twice daily	Start 14 days before, continue ~6 months	Only in patients with prior HE [5]
IBS-D	550 mg three times daily	14 days	Can repeat up to 2 times [5,1]
Travelers' Diarrhea	200 mg three times daily	3 days	Only noninvasive E. coli [1]