Norgine Pharmaceuticals Limited and Alfa Wassermann are pleased to announce the launch of TARGAXAN® 550 in the UK – the only treatment available in the UK that is licensed for ‘the reduction in recurrence of episodes of overt hepatic encephalopathy (HE) in patients ≥ 18 years of age’,(1) a potentially life-threatening neuropsychiatric condition associated with liver disease.
The pivotal clinical trial by Bass et al (2010),(2) in which patients in remission from recurrent episodes of hepatic encephalopathy due to cirrhosis who were treated with TARGAXAN 550 mg twice-daily (bd) with or without lactulose*, were compared with patients given placebo (bd) with or without lactulose* over six months, demonstrated:
- A 58% relative reduction in the risk of breakthrough episodes of overt hepatic encephalopathy over 6 months (Hazard ratio 0.42; p<0.001). Thus the numbers needed to treat (NNT) = 4
- A 50% relative reduction in the risk of hospitalisations caused by HE over 6 months (Hazard ratio 0.50; p=0.01). Thus the numbers needed to treat (NNT) = 9
*91% of patients in both groups were taking lactulose.
Hepatic encephalopathy encompasses a spectrum of neuropsychiatric abnormalities seen in patients with established liver disease and is commonly associated with liver cirrhosis.(3,4) Patients with hepatic encephalopathy may experience symptoms ranging from subtle neurological abnormalities (e.g. mood alterations, changes in reaction times in daily activities such as driving), to severe neurological impairment (e.g. where a patient has difficulty moving and communicating) and in extreme cases patients may present with coma.(5)
Hepatic encephalopathy has been shown to have a significantly negative impact on patients’ health-related quality of life (HRQoL).(6–10) Indeed it has also been shown that a lower HRQoL may act as an indicator for further episodes of HE.(11)
- Liver disease is on the increase. In the UK there has been a 25% increase in liver deaths between 2001 and 2009.(12)
- This is in contrast to other major causes of death which have been in decline. Over 70% of patients with liver disease die in hospital.(12)
- A regularly used benchmark of cost, length of hospital stay, is prolonged for individuals with chronic liver disease, with a reported average of 10.2 days.(13)
- Hepatic encephalopathy was estimated to be responsible for 55,000 hospitalisations at a total cost of $1.2 billion per year in the US in 2007.(14)
TARGAXAN 550 is a gut specific antibiotic which targets Gram positive and Gram negative ammonia producing species. It is thought that it may inhibit the division of urea-deaminating bacteria, thereby reducing the production of ammonia and other compounds that are believed to be important in the development of hepatic encephalopathy.(1)
TARGAXAN 550 (Rifaximin-alpha) is available at an NHS price of £259.23 for a month’s supply of 56 tablets.
Andrew Langford, Chief Executive of the British Liver Trust, welcomes the increased use of TARGAXAN 550 for as many people with hepatic encephalopathy as is needed. Langford says “Liver disease in itself is a huge problem for people and their families to deal with but is a ‘double whammy’ when people go on to develop hepatic encephalopathy, which for many will seem like dementia and/or serious mental health illness.
Current treatment requires patients to take very large doses of laxatives which makes a ‘bad situation a lot worse’ and can lead to a lack of dignity and dehumanisation of the person with the encephalopathy. A universally used treatment that alleviates the symptoms of encephalopathy and does not have the severe side effects that current treatment has is going to have huge benefit to the health and quality of life of both the patients and their families.”
Andrew Burroughs, Consultant Physician and Professor of Hepatology at the Royal Free Hospital London says, “TARGAXAN 550 is an important drug that significantly improves quality of life for patients and their partners and families. It also reduces the repeated admissions to hospital that often these patients are subject to, and should result in cost savings to the NHS.”
The UK is the first European market in which Norgine enters the hepatic encephalopathy therapy area, with a medicine that has the potential to make a significant impact on treatment outcomes(2) and improve the quality of life for sufferers and their caregivers.(9)
Bob Cuffe, UK General Manager for Norgine, said “It is wonderful for Norgine to be able to bring to the market this medicine, with all its proven benefits, in such a short space of time. We believe TARGAXAN 550 has the potential to change the way in which UK patients with this debilitating condition are managed and we hope marks the first of many novel therapeutic agents that Norgine will bring to aid the fight against Liver Disease and its various complications”.
- 1TARGAXAN Summary of Product Characteristics, 2012.
- Bass, N.M., et al., Rifaximin treatment in hepatic encephalopathy. N Engl J Med, 2010; 362(12): 1071-81.
- Bajaj, J.S., et al., The multi-dimensional burden of cirrhosis and hepatic encephalopathy on patients and caregivers. Am J Gastroenterol, 2011; 106(9): 1646-53.
- Prakash, R. and K.D. Mullen, Mechanisms, diagnosis and management of hepatic encephalopathy. Nat Rev Gastroenterol Hepatol, 2010; 7(9): 515-25.
- Bajaj, J.S., Review article: the modern management of hepatic encephalopathy. Aliment Pharmacol Ther, 2010; 31(5): 537-47.
- Wein C, Koch H, Popp B, Oehler G, Schauder P. Minimal hepatic encephalopathy impairs fitness to drive. Hepatology. 2004;39(3):739-45
- Cash W, McConville P, McDermott E, McCormick P, Callender M, McDougall N. Current concepts in the assessment and treatment of Hepatic Encephalopathy. QJM. 2009
- Morgan M. 8: Hepatic Encephalopathy in Patients with Cirrhosis. In: Dooley JS, Lok A, Burroughs A, Heathcote J, editors. Sherlock’s Disease of the Liver and Biliary System. 12th ed: Blackwell Publishing Ltd.; 2011
- Blei AT, Córdoba J. Hepatic encephalopathy. The American Journal of Gastroenterology. 2001;96(7):1968-76
- Williams R. Review article: bacterial flora and pathogenesis in hepatic encephalopathy. Alimentary Pharmacology & Therapeutics. 2006;25(1):17-22. (in Biblio, copy printed)
- Sanyal, A., et al., Randomised clinical trial: rifaximin improves health-related quality of life in cirrhotic patients with hepatic encephalopathy – a double-blind placebo-controlled study. Aliment Pharmacol Ther, 2011; 34(8): 853-61.
- A. Burroughs, D. McNamara. Liver disease in Europe. Aliment Pharmacol Ther 2003; 18 (Suppl. 3): 54-59.
- E.Huang, E. Esrailian, B.M.R.Spigel. The cost-effectiveness and budget impact of competing therapies in hepatic encephalopathy – decision analysis. Alimentary Pharmacology & Therapeutics.2007; 1147-1161