What is the recommended dose of Xifaxan (Rifaximin) for hepatic encephalopathy and irritable bowel syndrome with diarrhea?

Recommended Dosage of Xifaxan (Rifaximin) for Hepatic Encephalopathy and IBS-D

For hepatic encephalopathy, the recommended dose of Xifaxan is 550 mg taken orally twice daily. For irritable bowel syndrome with diarrhea (IBS-D), the recommended dose is 550 mg taken orally three times daily for 14 days. 1

Dosing for Hepatic Encephalopathy

Rifaximin is FDA-approved for reducing the risk of overt hepatic encephalopathy recurrence in adults with advanced liver disease. The dosing regimen is:

• Dose: 550 mg tablet
• Frequency: Twice daily
• Duration: Long-term/maintenance therapy 1

Key evidence supporting this dosing:

• In a pivotal randomized controlled trial, rifaximin 550 mg twice daily for 6 months significantly reduced the risk of breakthrough hepatic encephalopathy episodes compared to placebo (22.1% vs 45.9%) 2
• This dosing regimen reduced HE-related hospitalizations (13.6% vs 22.6%) 2
• Most patients (>90%) in clinical trials received concomitant lactulose therapy 2

While one small study suggested once-daily dosing might be comparable to twice-daily dosing for HE prevention 3, the FDA-approved regimen with stronger evidence remains twice daily 1.

Dosing for IBS-D

For IBS-D, rifaximin is prescribed as:

• Dose: 550 mg tablet
• Frequency: Three times daily
• Duration: 14 days 1
• Retreatment: Patients who experience symptom recurrence can be retreated up to two additional times with the same dosage regimen 1, 4

The American Gastroenterological Association (AGA) and British Society of Gastroenterology both recommend rifaximin as an efficacious second-line drug for IBS-D in secondary care 4. Clinical trials demonstrated that rifaximin had a significantly greater response based on the FDA responder endpoint for IBS-D compared to placebo 4.

Clinical Considerations and Caveats

For Hepatic Encephalopathy:

• Rifaximin has not been extensively studied in patients with MELD scores >25, and only 8.6% of patients in controlled trials had MELD scores over 19 1
• There is increased systemic exposure in patients with more severe hepatic dysfunction 1
• Can be used as add-on therapy to lactulose when lactulose alone fails, or alone in patients who cannot tolerate lactulose 5

For IBS-D:

• Effect on abdominal pain may be limited compared to its effect on diarrhea symptoms 4, 5
• Adverse events are comparable to placebo, with most common effects including abdominal pain, diarrhea, headache, and upper respiratory tract infection (occurring in <10% of patients) 6

General Precautions:

• Not effective for travelers' diarrhea due to Campylobacter jejuni, Shigella spp., or Salmonella spp. 1
• Monitor for Clostridium difficile-associated diarrhea, especially in patients with risk factors 1
• Can be taken with or without food 1

Algorithm for Selection

1. For hepatic encephalopathy:

   • First-line: Lactulose
   • Add rifaximin 550 mg twice daily if:
     • Patient has recurrent episodes despite lactulose
     • Patient has had ≥1 additional episodes of overt HE within 6 months

2. For IBS-D:

   • First-line: Dietary modifications, fiber supplements, antidiarrheals
   • Second-line: Rifaximin 550 mg three times daily for 14 days if:
     • First-line treatments fail
     • Patient has moderate symptoms without alarm features
   • Consider retreatment (up to 2 additional courses) if symptoms recur after initial response

By following these evidence-based dosing recommendations, clinicians can optimize treatment outcomes while minimizing adverse effects for patients with hepatic encephalopathy or IBS-D.