13th March 2017

Guidelines

Hepatic encephalopathy in chronic liver disease – American Association for the Study of Liver Diseases/European Association for the Study of the Liver (AASLD/EASL) Practice Guideline 1

“Hepatic encephalopathy (HE) is a frequent complication and one of the most debilitating manifestations of liver disease”

“Overt hepatic encephalopathy will occur in 30-40% of those with cirrhosis at some time during their clinical course”

The guidelines recommend rifaximin-α (with lactulose) to maintain remission in patients who have experienced one or more bouts of overt hepatic encephalopathy.

View the full AASLD/EASL guidance

National Institute for Health and Care Excellence (NICE) NG50: Cirrhosis in over 16s: assessment and management 2

“Hepatic encephalopathy is a major complication of cirrhosis.”

“Approximately 50% of people with cirrhosis will develop clinically apparent hepatic encephalopathy at some stage after diagnosis – the risk being around 5-25% within 5 years.”

“Hospital admissions are common and inpatient stays often prolonged. The presence of hepatic encephalopathy is associated with a significant increase in mortality; survival after the first episode is 42% at 1 year and 23% at 3 years.” 2

View the full NG50 guidance

NICE TA337 guidance 3 for preventing episodes of overt hepatic encephalopathy with XIFAXAN® 550 (rifaximin-α)

Section 1.1 recommends rifaximin-α, within its marketing authorisation, as an option for reducing the recurrence of episodes of overt hepatic encephalopathy in people aged 18 years or older. 3

Costing Report TA337, Section 2.5:
“Expert clinical opinion suggests that rifaximin-α is effective in reducing the recurrence of hepatic encephalopathy episodes and is well tolerated. Treatment with rifaximin-α may improve quality of life, prevent readmissions to hospital and reduce morbidity and carer burden.” 4

Evidence supporting HE management with rifaximin-α around the UK:

Scottish Medicines Consortium (SMC): Rifaximin-α (XIFAXAN®) is accepted for use within NHS Scotland. 5

National Centre for Pharmacoeconomics (NCPE) Ireland: Product accepted but full pharmacoeconomic evaluation not recommended 6

The Department of Health Social Services and Public Safety (DHSSPS) DHSSPS have endorsed NICE TA337 in Northern Ireland. 7/sup>

All Wales Medicines Strategy Group (AWMSG): Product meets exclusion criteria due to positive NICE appraisal. 8

Complications of liver cirrhosis – German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS) 9

The guidelines recommend rifaximin-α as an additive to lactulose in the secondary prophylaxis of HE > grade 1 according to West Haven criteria without trigger, if a relapse has occurred with lactulose alone (recommendation 7.23).

View the full DGVS guidance

Hepatic encephalopathy – Danish Society for Gastroenterology and Hepatology (DSGH) 10

The guidelines recommend rifaximin-α twice daily as a supplement to lactulose after the second episode of OHE.

View the full DSGH guidance

Please check your local guidelines for appropriate recommendations on the management of HE in your country.

GL-HEP-XIF-2000173    April 2021
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Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard (United Kingdom) or www.hpra.ie (Ireland)

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Date of preparation: May 2020 Job Code: UKE-HEP-XIF-2000012 © 2019 Norgine

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Seven UK participating centres agreed a standardised data collection pro-forma. Patients with chronic liver disease who were treated with rifaximin-α for secondary prevention of overt hepatic encephalopathy (OHE) were included.* Details of all causes of HE and emergency hospital admissions were requested at 3, 6 and 12 months before and after rifaxamin-α initiation. Clinical data were recorded at baseline, at 3, 6 and 12 months before and after rifaximin-α initiation.
87% of patients (n=282) were taking concomitant lactulose.
*Some patients included were on 3 x 400 mg daily as this was prior to the launch of the K licensed dose of XIFAXAN® 550 mg twice a day.

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An observational study including 127 patients from the Netherlands. Conducted between September 2015 to May 2018.
AIM: To assess hospital resource use, bacterial infections and adverse events in the 6 months before and after rifaximin-α initiation in patients with overt hepatic encephalopathy.

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Costing Details

Inpatient costs were estimated in UK£ at 2013/14 prices from published NHS sources at a mean cost of £513(€569.43)* per day for non-elective admissions for liver disease.1

Rifaximin-α drug costs were calculated from the price published in the British National Formulary of £259(€287.75)* for 56 550mg tablets2, giving an annual drug treatment cost per patient of £3,379(€3750.69)* for the licensed dose of 550mg twice daily.

Please note that costs from this study were based on UK NHS sources and the UK BNF and have been calculated by using GBP to Euro conversion rate mentioned below. These prices may differ from local EU prices of XIFAXAN®.
*Values in Euros converted from values in Pound Sterling at an exchange rate of £1:€1.11 (correct as 03.11.20).

References

  1. NHS reference costs. Available at: www.gov.uk/government/publications/nhs-reference-costs-2013-to-2014, 2013-14
  2. Joint Formulary Committee. British National Formulary. Available at: https://bnf.nice.org.uk/medicinal-forms/rifaximin.html
A retrospective, observational, multicentre study including 145 patients from 11 UK NHS centres. Conducted from Aug 2014 to Jun 2015.
AIM: To compare resource use in the 6 and 12 months before and after rifaximin-α initiation in UK patients with HE.
INCLUSION CRITERIA: Clinical diagnosis of HE. HE diagnosed prior to rifaximin-α initiation. Initiated on rifaximin-α at least 12 months prior data collection.
EXCLUSION CRITERIA: Rifaximin-α initiated at other hospitals. Medical records unavailable.

Details of hospitalisations and hospital visits were extracted from NHS Trust electronic databases. Analysis included only alive patients at the end of 6 and 12 month periods.
IMPRESS study was sponsored and funded by Norgine

Rifaximin-α initiation dose was 1100mg/day (licensed dose) in 30%, 1200 mg/day in 64%, and other doses in 6% of patients, respectively.
This study included patients started on rifaximin-a prior to the launch of XIFAXAN® 550mg bd. 82% of patients (n=119) were taking concomitant lactulose at baseline.

An observational study including 127 patients from the Netherlands. Conducted between September 2015 to May 2018.
AIM: To assess hospital resource use, bacterial infections and adverse events in the 6 months before and after rifaximin-α initiation in patients with overt hepatic encephalopathy.

The study was sponsored by the Foundation for Liver and Gastrointestinal Research Rotterdam (SLO) to which an educational grant was provided by Norgine B.V., Amsterdam, the Netherlands.


Rifaximin-α initiation dose was 1100 mg per day (licensed dose) and was raised to 1650 mg per day in 11 patients due to recurrence of overt hepatic encephalopathy while on 1100 mg per day. 97.6% of patients (n=124) were taking concomitant lactulose at baseline.


* Optional use of lactulose (~90% patients in 'All rifaximin-α' group received concomitant lactulose).

References

  1. Vilstrup H, et al. Hepatology 2014;60(2):715-735
  2. National Institute for Health and Care Excellence (NICE). National guideline 50 – Cirrhosis in over 16s: assessment and management. July 2016. Available at: https://www.nice.org.uk/guidance/ng50/resources/cirrhosis-in-over-16s-assessment-and-management-1837506577093
  3. NICE. Technology appraisal guidance 337. Rifaximin for preventing episodes of overt hepatic encephalopathy. March 2015. Available at: https://www.nice.org.uk/guidance/ta337/resources/rifaximin-for-preventing-episodes-of-overt-hepatic-encephalopathy-82602552414661
  4. NICE. Costing report: Implementing the NICE guidance on rifaximin for preventing episodes of overt hepatic encephalopathy (TA337). Available at: https://nice.org.uk/guidance/ta337/resources/costing-report-428453677
  5. Scottish Medical Consortium. Advice regarding rifaximin 550mg film coated tablets (TARGAXAN®). 2013. SMC No. (893/13). Available at: http://www.scottishmedicines.org.uk/files/advice/rifaximin_Targaxan_FINAL_August_2013_for_website.pdf
  6. National Centre for Pharmacoeconomics, NCPE Ireland, Pharmacoeconomic Evaluation of Rifaximin (TARGAXAN®). Available at: http://www.ncpe.ie/drugs/rifaximin-targaxan-2/
  7. The Department of Health Social Services and Public Safety (DHSSPS). Available at: https://www.health-ni.gov.uk/articles/nice-endorsed-technology-appraisals-20152016
  8. All Wales Strategy Medicines Group. Appraisal information, Reference no. 1058, rifaximin (TARGAXAN®). Available at: http://www.awmsg.org/awmsgonline/app/appraisalinfo/1058
  9. German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS). Complications of liver cirrhosis (AWMF No. 021-017). Available at: https://www.awmf.org/uploads/tx_szleitlinien/021-017l_S2k_Komplikationen-der-Leberzirrhose_2019-04.pdf
  10. Danish Society for Gastroenterology and Hepatology (DSGH). Hepatic Encephalopathy. Available at: https://www.dsgh.dk/index.php/lever/hepatisk-encephalopati