When to start Riximin (Rifaximin)?

When to Start Rifaximin

Rifaximin should be started for secondary prophylaxis after a patient with cirrhosis has experienced at least one episode of overt hepatic encephalopathy (HE) that has resolved, typically added to lactulose therapy at a dose of 550 mg twice daily. 1, 2

Primary Indications for Initiating Rifaximin

Hepatic Encephalopathy Prevention

• Start rifaximin 550 mg twice daily as secondary prophylaxis following the first resolved episode of overt HE in patients with cirrhosis, particularly when added to lactulose therapy 1, 2
• Consider rifaximin for prophylaxis 14 days prior to non-urgent TIPS placement in patients with cirrhosis and previous episodes of overt HE, continuing for approximately 6 months post-procedure 1
• The combination of rifaximin plus lactulose reduces HE recurrence risk by 58% compared to placebo and significantly decreases HE-related hospitalizations (hazard ratio 0.50) 2
• Do not use rifaximin as monotherapy for acute overt HE episodes—lactulose remains the cornerstone of acute treatment 2, 3

IBS-D (Irritable Bowel Syndrome with Diarrhea)

• 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 1
• Rifaximin can be retreated up to 2 times with the same dosage regimen if symptoms recur after initial response 1
• The number-needed-to-treat is 11 for IBS-D symptom relief 1

Travelers' Diarrhea

• Start rifaximin 200 mg three times daily for 3 days at the onset of travelers' diarrhea symptoms caused by noninvasive strains of E. coli in patients ≥12 years old 4, 5
• Rifaximin significantly reduces time to last unformed stool (32.0 hours vs 65.5 hours with placebo, p=0.001) 5

Clinical Algorithm for HE Management

Step 1: First Episode of Overt HE

• Initiate lactulose 30-45 mL (20-30 g) every 1-2 hours until achieving 2-3 soft bowel movements daily 2, 3
• Add rifaximin 550 mg twice daily to lactulose for enhanced prevention of recurrence 1, 2

Step 2: Recurrent Episodes (≥2 episodes within 6 months)

• Strongly recommend adding rifaximin 550 mg twice daily to ongoing lactulose therapy if not already prescribed 1, 3
• This combination shows superior recovery rates (76% vs 44%, p=0.004) and shorter hospital stays (5.8 vs 8.2 days, p=0.001) compared to lactulose alone 3

Step 3: Lactulose Intolerance

• Consider rifaximin 550 mg twice daily as monotherapy only when lactulose is poorly tolerated, though this is based on expert opinion rather than robust evidence 2, 3

Important Contraindications and Precautions

When NOT to Start Rifaximin

• Do not use for acute severe HE (West-Haven grade 3 or higher) when patients cannot take oral medications—use lactulose enemas instead (300 mL lactulose mixed with 700 mL water) 2, 3
• Do not use as monotherapy for acute overt HE episodes regardless of severity 2
• Rifaximin is not suitable for treating systemic bacterial infections due to minimal systemic absorption (<0.4%) 4, 6

Hepatic Impairment Considerations

• Systemic exposure increases 10-fold in Child-Pugh Class A, 14-fold in Class B, and 21-fold in Class C hepatic impairment compared to healthy volunteers 4
• Despite increased absorption, no dosage adjustment is recommended because rifaximin acts locally in the gastrointestinal tract 4
• Exercise caution when administering to patients with severe hepatic impairment (Child-Pugh Class C) 4

Common Pitfalls to Avoid

• Avoid prescribing rifaximin alone for acute HE episodes—this is the most common error, as lactulose must remain the foundation of acute treatment 2, 3
• Do not delay adding rifaximin after the first HE episode—early addition to lactulose provides optimal prevention of recurrence 1, 2
• Do not use rifaximin for dysenteric or invasive bacterial diarrhea—it shows lower activity against these pathogens 5, 6
• Avoid using rifaximin in IBS-C (constipation-predominant IBS)—it is FDA-approved only for IBS-D 1

Special Clinical Scenarios

Pre-TIPS Prophylaxis

• Initiate rifaximin 600 mg twice daily starting 14 days before TIPS placement in patients with previous overt HE episodes 1
• This significantly reduces post-TIPS HE incidence (34% vs 53% with placebo) 1
• Continue therapy for approximately 6 months post-procedure, though optimal duration beyond 6 months remains undefined 1

Recurrent CDI (Clostridium difficile Infection)

• Consider rifaximin following oral vancomycin for multiply recurrent CDI in adults, though pediatric data are limited 1
• Rifaximin does not increase risk of C. difficile-associated colitis based on 13 randomized controlled trials 2

Dosing Summary by Indication

Indication	Dose	Duration	Key Evidence
HE Prevention	550 mg twice daily	Long-term	[1,2]
Pre-TIPS Prophylaxis	600 mg twice daily	Start 14 days before, continue ~6 months	[1]
IBS-D	550 mg three times daily	14 days (can repeat up to 2×)	[1]
Travelers' Diarrhea	200 mg three times daily	3 days	[4,5]