Rifaximin

To reduce the development of drug-resistant bacteria and maintain the effectiveness of XIFAXAN and other antibacterial drugs, XIFAXAN when used to treat infection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. XIFAXAN is a rifamycin antibacterial indicated for: • Treatment of travelers’ diarrhea (TD) caused by noninvasive strains of Escherichia coli in adult and pediatric patients 12 years of age and older. • Reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults.

Rifaximin is an antibacterial drug.

Condition Recommended Oral Dosage TD 200 mg 3 times a day for 3 days HE 550 mg 2 times a day IBS-D 550 mg 3 times a day for 14 days. Patients who experience recurrence can be retreated up to 2 times with the same regimen. XIFAXAN can be taken with or without food.

XIFAXAN is contraindicated in patients with a hypersensitivity to rifaximin, any of the rifamycin antimicrobial agents, or any of the components in XIFAXAN. Hypersensitivity reactions have included exfoliative dermatitis, angioneurotic edema, and anaphylaxis. History of hypersensitivity to rifaximin, rifamycin antimicrobial agents, or any of the components of XIFAXAN.

• Travelers’ Diarrhea Not Caused by E. coli: XIFAXAN was not effective in diarrhea complicated by fever and/or blood in the stool or diarrhea due to pathogens other than E. coli. If diarrhea symptoms get worse or persist for more than 24 to 48 hours, discontinue XIFAXAN and consider alternative antibiotics. • Clostridium difficile -Associated Diarrhea: Evaluate if diarrhea occurs after therapy or does not improve or worsens during therapy. • Hepatic Impairment: Use with caution in patients with severe (Child-Pugh Class C) hepatic impairment. • Concomitant P-glycoprotein (P-gp) inhibitors (e.g., cyclosporine): Caution should be exercised when concomitant use of XIFAXAN and a P-glycoprotein inhibitor is needed.

The following clinically significant adverse reactions are described elsewhere in labeling: • Clostridium difficile -associated diarrhea Most common adverse reactions: • TD (≥2%): Headache. • HE (≥10%): Peripheral edema, nausea, constipation, dizziness, fatigue, urinary tract infection, insomnia, anemia, pruritus, and ascites. • IBS-D (≥2%): ALT increased, nausea

Warfarin: Monitor INR and prothrombin time, dose adjustment of warfarin may be needed to maintain target INR range. P-glycoprotein Inhibitors Concomitant administration of cyclosporine, an inhibitor of P-gp and OATPs significantly increased the systemic exposure of rifaximin. In patients with hepatic impairment, a potential additive effect of reduced metabolism and concomitant P-gp inhibitors may further increase the systemic exposure to rifaximin. Caution should be exercised when concomitant use of XIFAXAN and a P-gp inhibitor such as cyclosporine is needed. Warfarin Changes in INR have been reported postmarketing in patients receiving rifaximin and warfarin concomitantly. Monitor INR and prothrombin time. Dose adjustment of warfarin may be needed to maintain target INR range. See prescribing information for warfarin.

Storage Store XIFAXAN Tablets at 20° to 25°C (68° to 77°F), excursions permitted to 15° to 30°C (59° to 86°F).