What is Rifaximin?

Rifaximin: A Gastrointestinal-Selective Antibiotic

Rifaximin is a poorly absorbed, broad-spectrum oral antibiotic that acts by binding to bacterial DNA-dependent RNA polymerase, inhibiting bacterial protein synthesis, and is FDA-approved for travelers' diarrhea, irritable bowel syndrome with diarrhea (IBS-D), and hepatic encephalopathy. 1, 2, 3

Pharmacological Properties

• Rifaximin is a rifamycin derivative that maintains high concentration in the intestine due to minimal systemic absorption (<1%), allowing it to remain active until excretion 2, 3
• It works by binding to the beta-subunit of bacterial DNA-dependent RNA polymerase, blocking transcription and inhibiting bacterial protein synthesis 3
• Rifaximin has activity against Gram-positive, Gram-negative, and anaerobic bacteria, with particular efficacy against diarrheagenic Escherichia coli 3, 4

FDA-Approved Indications

Travelers' Diarrhea

• Recommended dosage: 200 mg three times daily for 3 days 1, 3
• Effective for non-invasive diarrheagenic Escherichia coli but should NOT be used where invasive pathogens are common 1
• Has comparable efficacy to fluoroquinolones for travelers' diarrhea with a superior safety profile 1

Irritable Bowel Syndrome with Diarrhea (IBS-D)

• Recommended dosage: 550 mg three times daily for 14 days 1, 2
• Patients with symptom recurrence can be retreated up to 2 times with the same regimen 1
• Significantly improves IBS-D symptoms including bloating and abdominal pain compared to placebo 1

Hepatic Encephalopathy

• Recommended dosage: 550 mg twice daily as add-on therapy to lactulose for prevention of recurrent hepatic encephalopathy 1, 2
• Reduces risk of recurrent hepatic encephalopathy by 58% when added to lactulose therapy 1
• Should be used alone for prevention only when lactulose is poorly tolerated 1
• For covert hepatic encephalopathy, treatment with lactulose or rifaximin is suggested to improve quality of life and reduce risk of overt hepatic encephalopathy 5

Safety Profile

• Excellent safety profile due to minimal systemic absorption (<1%) 1, 6
• Limited drug interactions; does not significantly affect intestinal or hepatic CYP3A4 activity 3
• Development of bacterial resistance appears to be limited due to minimal systemic absorption and limited cross-resistance with other antimicrobials 6
• May slightly reduce the effectiveness of oral contraceptives containing ethinyl estradiol and norgestimate (Cmax reduced by 25% and 13%, respectively) 3

Emerging Applications

• Small bowel bacterial overgrowth syndrome 6, 4
• Uncomplicated diverticular disease and prevention of recurrent diverticulitis 6
• Inflammatory bowel disease and pouchitis 7, 8

Clinical Considerations

• For hepatic encephalopathy, first-line treatment remains lactulose, with rifaximin added if lactulose alone fails in prevention 1
• Rifaximin should not be used for dysentery or febrile invasive diarrheal disease regardless of illness severity 1
• The drug has moderate protective effectiveness as prophylaxis in regions where Campylobacteriosis is common 1
• Rifaximin has shown efficacy in treating portal systemic encephalopathy with an excellent safety profile 8

Rifaximin's unique properties of high gastrointestinal concentration with minimal systemic absorption make it particularly valuable for treating localized gastrointestinal infections and conditions while minimizing systemic side effects and antimicrobial resistance concerns 6, 7.