What conditions are treated with Xifaxin (Rifaximin)?

Xifaxin (Rifaximin) Indications

Xifaxin treats three FDA-approved conditions: travelers' diarrhea caused by noninvasive E. coli, prevention of recurrent hepatic encephalopathy in cirrhotic patients, and irritable bowel syndrome with diarrhea (IBS-D) in adults. 1

FDA-Approved Indications

Travelers' Diarrhea

• Xifaxin 200 mg three times daily for 3 days treats travelers' diarrhea caused by noninvasive strains of Escherichia coli in patients 12 years and older 1
• Do NOT use if diarrhea is complicated by fever, blood in stool, or caused by invasive pathogens (treatment failure rates up to 50% in these cases) 1, 2
• Rifaximin is ineffective against Campylobacter jejuni and should not be used for dysentery regardless of severity 2, 3
• If symptoms worsen or persist beyond 24-48 hours, discontinue and consider alternative antibiotics 1

Hepatic Encephalopathy (HE)

• Xifaxin 550 mg twice daily reduces risk of overt HE recurrence in adults with cirrhosis 1
• Rifaximin is an add-on therapy to lactulose, not first-line monotherapy—91% of trial patients used concomitant lactulose 1, 4
• Reduced recurrent HE risk by 58% compared to placebo when combined with lactulose 4, 2
• Use rifaximin alone only when lactulose is poorly tolerated 4, 2
• For acute overt HE, first-line treatment remains lactulose; rifaximin cannot be recommended as monotherapy due to study biases 4
• Not studied in patients with MELD scores >25; only 8.6% of trial patients had MELD >19 1
• Use with caution in Child-Pugh Class C hepatic impairment due to increased systemic exposure 1

Irritable Bowel Syndrome with Diarrhea (IBS-D)

• Xifaxin 550 mg three times daily for 14 days treats IBS-D in adults 1, 2
• Patients with symptom recurrence after initial response can be retreated up to 2 times with the same regimen 1, 2
• Demonstrated significant improvement in bloating (RR 0.86) and abdominal pain (RR 0.87) compared to placebo 2
• Showed 40.7% adequate global symptom relief versus 31.7% with placebo (P<.001) 5

Mechanism Beyond Antibacterial Action

• Rifaximin is minimally absorbed (<0.4%), achieving fecal concentrations of 8000 μg/g after 3 days 6
• Acts as a gut microenvironment modulator by reducing bacterial translocation across intestinal epithelium 5
• Activates pregnane X receptor (PXR), down-regulating proinflammatory nuclear factor κB signaling 5, 7
• Decreases bacterial adherence and internalization without necessarily altering bacterial counts 5

Safety Profile

• Excellent safety profile due to minimal systemic absorption 2
• No increased risk of Clostridium difficile infection or bacterial resistance in long-term use 4
• Most common adverse reactions: headache (TD), peripheral edema/nausea/dizziness (HE), elevated ALT/nausea (IBS-D) 1
• Contraindicated in patients with hypersensitivity to rifaximin, rifamycin antimicrobials, or any component 1
• Exercise caution with concomitant P-glycoprotein inhibitors (e.g., cyclosporine) 1
• Monitor INR and prothrombin time with warfarin; dose adjustment may be needed 1