Xifaxan

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 can be taken with or without food. (

XIFAXAN is a pink-colored biconvex tablet and is available in the following strengths:

• 200 mg – a round tablet debossed with “Sx” on one side and plain on the other.
• 550 mg – an oval tablet debossed with “rfx” on one side and plain on the other.

Pregnancy: May cause fetal harm (

• 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. (
  
  
  5.1 Travelers’ Diarrhea Not Caused by

  Escherichia coli

  XIFAXAN was not found to be effective in patients with diarrhea complicated by fever and/or blood in the stool or diarrhea due to pathogens other than

  Escherichia coli.

  Discontinue XIFAXAN if diarrhea symptoms get worse or persist more than 24 to 48 hours and alternative antibiotic therapy should be considered.

  XIFAXAN is not effective in cases of travelers’ diarrhea due to

  Campylobacter jejuni

  . The effectiveness of XIFAXAN in travelers’ diarrhea caused by

  Shigella

  spp. and

  Salmonella

  spp. has not been proven. XIFAXAN should not be used in patients where

  Campylobacter jejuni, Shigella

  spp., or

  Salmonella

  spp. may be suspected as causative pathogens [

  see Indications and Usage ].
  )
  
• Clostridium difficile
  -Associated Diarrhea: Evaluate if diarrhea occurs after therapy or does not improve or worsens during therapy. (
  
  
  5.2

  Clostridium difficile-

  Associated Diarrhea

  Clostridium difficile-

  associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including XIFAXAN, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon which may lead to overgrowth of

  C. difficile.

  C. difficile

  produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of

  C. difficile

  cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

  If CDAD is suspected or confirmed, ongoing antibiotic use not directed against

  C. difficile

  may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C

  . difficile,

  and surgical evaluation should be instituted as clinically indicated.
  )
  
• Hepatic Impairment: Use with caution in patients with severe (Child-Pugh Class C) hepatic impairment. (
  
  
  5.4 Severe (Child-Pugh Class C) Hepatic Impairment

  There is increased systemic exposure in patients with severe hepatic impairment. The clinical trials were limited to patients with MELD scores <25. Therefore, caution should be exercised when administering XIFAXAN to patients with severe hepatic impairment (Child-Pugh Class C) [

  see Use in Specific Populations , Clinical Studies ].
  ,
  
  
  8.7 Hepatic Impairment

  Following administration of XIFAXAN 550 mg twice daily to patients with a history of hepatic encephalopathy, the systemic exposure (i.e., AUC_τ) of rifaximin was about 10-, 14-, and 21-fold higher in those patients with mild (Child-Pugh Class A), moderate (Child-Pugh Class B) and severe (Child-Pugh Class C) hepatic impairment, respectively, compared to that in healthy volunteers. No dosage adjustment is recommended because rifaximin is presumably acting locally. Nonetheless, caution should be exercised when XIFAXAN is administered to patients with severe hepatic impairment

  [see Warnings and Precautions , Clinical Pharmacology , Clinical Studies ]

  .
  )
  
• 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. (
  
  
  5.5 Concomitant Use with P-glycoprotein Inhibitors

  Concomitant administration of drugs that are P-glycoprotein (P-gp) inhibitors with XIFAXAN can substantially 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. 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

  [see Drug Interactions , Clinical Pharmacology ].
  7.1 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

  [see Warnings and Precautions , Clinical Pharmacology (

  12.3

  )].
  )