What is HE?

Hepatic encephalopathy (HE) is a brain dysfunction caused by liver insufficiency and/or portosystemic shunting.1 In patients with cirrhosis and decreased hepatic function, toxins from the gut can enter the bloodstream and reach the brain, where they affect neurotransmission.1-3 This can cause episodes of HE, which may present as alterations in consciousness, cognition, and behavior that range from minimal to severe.1-3

HE is a problem hiding in plain sight

Recognizing patients at risk. The risk of HE is higher in patients with cirrhosis/chronic liver disease and4:

  • Portal hypertension
  • Ascites
  • Variceal bleeding
  • Medications, such as opioids

The risk of HE recurrence is high1,5,6

Once overt HE occurs, patients have a high risk of recurrence1,5,6:

  • Cumulative risk of an overt HE recurrence at 1 year: 40%
  • 40% cumulative risk of another overt HE recurrence within 6 months, despite standard-of-care treatment

HE and overt HE can be a burden for patients and families

  • Overt HE may cause irreversible damage1,7,8
  • HE-related hospitalizations rose 325% from 2005 to 20149*
  • Other costs: disability, lost productivity, stress on caregivers10

*ICD-9-CM codes at hospital discharge: 291.2 (alcohol-induced persisting dementia), 348.3 (encephalopathy, unspecified), and 572.2 (hepatic encephalopathy); all listed diagnoses.

HE = hepatic encephalopathy

AASLD = American Association for the Study of Liver Diseases

INDICATIONS

XIFAXAN® (rifaximin) 550 mg tablets are indicated for the reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults and for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults.

IMPORTANT SAFETY INFORMATION
  • XIFAXAN is contraindicated in patients with a hypersensitivity to rifaximin, rifamycin antimicrobial agents, or any of the components in XIFAXAN. Hypersensitivity reactions have included exfoliative dermatitis, angioneurotic edema, and anaphylaxis.
  • 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. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued.
  • There is an increased systemic exposure in patients with severe (Child-Pugh Class C) hepatic impairment. Caution should be exercised when administering XIFAXAN to these patients.
  • Caution should be exercised when concomitant use of XIFAXAN and P-glycoprotein (P-gp) and/or OATPs inhibitors is needed. 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.
  • In clinical studies, the most common adverse reactions for XIFAXAN were:
    • HE (≥10%): Peripheral edema (15%), nausea (14%), dizziness (13%), fatigue (12%), and ascites (11%)
    • IBS-D (≥2%): Nausea (3%), ALT increased (2%)
  • INR changes have been reported in patients receiving rifaximin and warfarin concomitantly. Monitor INR and prothrombin time. Dose adjustment of warfarin may be required.
  • XIFAXAN may cause fetal harm. Advise pregnant women of the potential risk to a fetus.

To report SUSPECTED ADVERSE REACTIONS, contact Salix Pharmaceuticals at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please click here for full Prescribing Information.

References: 1. Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014;60(2):715-735. 2. Vince AJ, Burridge SM. Ammonia production by intestinal bacteria: the effects of lactose, lactulose and glucose. J Med Microbiol. 1980;13(2):177-191. 3. Khan A, Ayub M, Khan WM. Hyperammonemia is associated with increasing severity of both liver cirrhosis and hepatic encephalopathy. Int J Hepatol. 2016;2016:6741754. 4. Tapper EB, Henderson JB, Parikh ND, Ioannou GN, Lok AS. Incidence of and risk factors for hepatic encephalopathy in a population-based cohort of Americans with cirrhosis. Hepatol Commun. 2019;3(11):1510-1519. 5. Sharma BC, Sharma P, Agrawal A, Sarin SK. Secondary prophylaxis of hepatic encephalopathy: an open-label randomized controlled trial of lactulose versus placebo. Gastroenterology. 2009;137(3):885-891. 6. Cordoba J, Ventura-Cots M, Simón-Talero M, et al; CANONIC Study Investigators of EASL-CLIF Consortium. Characteristics, risk factors, and mortality of cirrhotic patients hospitalized for hepatic encephalopathy with and without acute-on-chronic liver failure (ACLF). J Hepatol. 2014;60(2):275-281. 7. Bajaj JS, Schubert CM, Heuman DM, et al. Persistence of cognitive impairment after resolution of overt hepatic encephalopathy. Gastroenterology. 2010;138(7):2332-2340. 8. Nardelli S, Allampati S, Riggio O, et al. Hepatic encephalopathy is associated with persistent learning impairments despite adequate medical treatment: a multicenter, international study. Dig Dis Sci. 2017;62(3):794-800. 9. Healthcare Cost and Utilization Project. Overview of the Nationwide Readmissions Database (NRD). https://www.hcup-us.ahrq.gov/nrdoverview.jsp. Accessed January 10, 2019. 10. Bajaj JS, Wade JB, Gibson DP, et al. The multi-dimensional burden of cirrhosis and hepatic encephalopathy on patients and caregivers. Am J Gastroenterol. 2011;106(9):1646-1653. 11. Romero-Gómez M, Boza F, García-Valdecasas MS, García E, Aguilar-Reina J. Subclinical hepatic encephalopathy predicts the development of overt hepatic encephalopathy. Am J Gastroenterol. 2001;96(9):2718-2723.

INDICATIONS

XIFAXAN® (rifaximin) 550 mg tablets are indicated for the reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults and for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults.

IMPORTANT SAFETY INFORMATION
  • XIFAXAN is contraindicated in patients with a hypersensitivity to rifaximin, rifamycin antimicrobial agents, or any of the components in XIFAXAN. Hypersensitivity reactions have included exfoliative dermatitis, angioneurotic edema, and anaphylaxis.
  • 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. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued.