Drugs in Focus
The Use of Racecadotril in Paediatric Gastrointestinal Disease
Corina Pienar
Department of Paediatrics, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania
“Pius Branzeu” County Emergency Hospital, Timisoara, Romania
Search for more papers by this authorMarc A. Benninga
Department of Paediatric Gastroenterology and Nutrition, Emma Children's Hospital Amsterdam, Amsterdam, the Netherlands
University Medical Centre, Amsterdam, the Netherlands
Search for more papers by this authorIlse J. Broekaert
Department of Paediatrics, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany
Search for more papers by this authorJernej Dolinsek
Department of Paediatrics, Gastroenterology, Hepatology and Nutrition Unit, University Medical Centre Maribor, Ljubljanska
Department of Paediatrics, Medical Faculty, University of Maribor, Taborska, Maribor, Slovenia
Search for more papers by this authorEmmanuel Mas
IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France et Unité de Gastroentérologie, Hépatologie, Nutrition, Diabétologie et Maladies Héréditaires du Métabolisme, France
Hôpital des Enfants, CHU de Toulouse, France
Search for more papers by this authorErasmo Miele
Department of Translational Medical Science, Section of Paediatrics, University of Naples “Federico II”, Naples, Italy
Search for more papers by this authorRok Orel
Department of Gastroenterology, Hepatology and Nutrition, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia
Medical Faculty, University of Ljubljana, Ljubljana, Slovenia
Search for more papers by this authorCarmen Ribes-Koninckx
Paediatric Gastroenterology, Hepatology and Nutrition Unit, La Fe University Hospital, Valencia, Spain
Search for more papers by this authorRut-Anne Thomassen
Pediatric Nutrition and Dietetics Unit, Department of Pediatric Medicine, Oslo University Hospital, Norway
Search for more papers by this authorMike Thomson
Department of Paediatric Gastroenterology, Sheffield Children's NHS Foundation Trust, Western Bank, Sheffield, UK
Search for more papers by this authorChristos Tzivinikos
Al Jalila Children's Specialty Hospital, Dubai, UAE
Search for more papers by this authorCorresponding Author
Nikhil Thapar
UCL Great Ormond Street Institute of Child Health, London, UK
Neurogastroenterology and Motility Unit, Department of Gastroenterology, Great Ormond Street Hospital, London, UK
Department of Paediatric Gastroenterology, Hepatology and Liver Transplant, Queensland Children's Hospital, Brisbane, Australia
Address correspondence and reprint requests to Dr Nikhil Thapar, Associate Professor and Honorary Consultant in Paediatric Gastroenterology, Great Ormond Street Hospital NHS Foundation Trust, Great Ormond Street, London WC1N 3JH, UK (e-mail: [email protected]).Search for more papers by this authorCorina Pienar
Department of Paediatrics, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania
“Pius Branzeu” County Emergency Hospital, Timisoara, Romania
Search for more papers by this authorMarc A. Benninga
Department of Paediatric Gastroenterology and Nutrition, Emma Children's Hospital Amsterdam, Amsterdam, the Netherlands
University Medical Centre, Amsterdam, the Netherlands
Search for more papers by this authorIlse J. Broekaert
Department of Paediatrics, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany
Search for more papers by this authorJernej Dolinsek
Department of Paediatrics, Gastroenterology, Hepatology and Nutrition Unit, University Medical Centre Maribor, Ljubljanska
Department of Paediatrics, Medical Faculty, University of Maribor, Taborska, Maribor, Slovenia
Search for more papers by this authorEmmanuel Mas
IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France et Unité de Gastroentérologie, Hépatologie, Nutrition, Diabétologie et Maladies Héréditaires du Métabolisme, France
Hôpital des Enfants, CHU de Toulouse, France
Search for more papers by this authorErasmo Miele
Department of Translational Medical Science, Section of Paediatrics, University of Naples “Federico II”, Naples, Italy
Search for more papers by this authorRok Orel
Department of Gastroenterology, Hepatology and Nutrition, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia
Medical Faculty, University of Ljubljana, Ljubljana, Slovenia
Search for more papers by this authorCarmen Ribes-Koninckx
Paediatric Gastroenterology, Hepatology and Nutrition Unit, La Fe University Hospital, Valencia, Spain
Search for more papers by this authorRut-Anne Thomassen
Pediatric Nutrition and Dietetics Unit, Department of Pediatric Medicine, Oslo University Hospital, Norway
Search for more papers by this authorMike Thomson
Department of Paediatric Gastroenterology, Sheffield Children's NHS Foundation Trust, Western Bank, Sheffield, UK
Search for more papers by this authorChristos Tzivinikos
Al Jalila Children's Specialty Hospital, Dubai, UAE
Search for more papers by this authorCorresponding Author
Nikhil Thapar
UCL Great Ormond Street Institute of Child Health, London, UK
Neurogastroenterology and Motility Unit, Department of Gastroenterology, Great Ormond Street Hospital, London, UK
Department of Paediatric Gastroenterology, Hepatology and Liver Transplant, Queensland Children's Hospital, Brisbane, Australia
Address correspondence and reprint requests to Dr Nikhil Thapar, Associate Professor and Honorary Consultant in Paediatric Gastroenterology, Great Ormond Street Hospital NHS Foundation Trust, Great Ormond Street, London WC1N 3JH, UK (e-mail: [email protected]).Search for more papers by this authorABSTRACT
Acute diarrhoea is a leading cause of morbidity and mortality in the paediatric population. Racecadotril is an antisecretory drug recommended as an adjuvant antidiarrhoeal treatment.
In the small bowel, the enzyme neutral endopeptidase (NEP) inhibits the action of enkephalins, which prevent water and electrolyte hypersecretion. By inhibiting NEP, racecadotril allows enkephalins to exhibit their antisecretory effects. Consequently, racecadotril reduces the secretion of water and electrolytes in the small intestine, without having an effect on intestinal motility. No serious adverse events related to racecadotril have been reported.
Racecadotril has proven its efficacy as an adjuvant antidiarrhoeal drug with a good safety profile. Its addition to oral rehydration solution (ORS) appears clinically beneficial and potentially leads to health care savings.
REFERENCES
- 1. GBD Collaborators. Estimates of global, regional, and national morbidity, mortality, and aetiologies of diarrhoeal diseases: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Infect Dis 2017; 17: 909–948.
- 2.Ogilvie I, Khoury H, Goetghebeur MM, et al. Burden of community-acquired and nosocomial rotavirus gastroenteritis in the pediatric population of Western Europe: a scoping review. BMC Infect Dis 2012; 12: 62.
- 3.Braeckman T, Van Herck K, Meyer N, et al. Rota Bel Study Group. Effectiveness of rotavirus vaccination in prevention of hospital admissions for rotavirus gastroenteritis among young children in Belgium: case-control study. BMJ 2012; 345: e4752.
- 4.Guarino A, Ashkenazi S, Gendrel D, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition/European Society for Pediatric Infectious Diseases evidence-based guidelines for the management of acute gastroenteritis in children in Europe: update 2014. J Pediatr Gastroenterol Nutr 2014; 59: 132–152.
- 5.Freedman SB, Williamson-Urquhart S, Farion KJ, et al. PERC PROGUT Trial Group. Multicenter Trial of a combination probiotic for children with gastroenteritis. N Engl J Med 2018; 379: 2015–2026.
- 6.Schnadower D, Tarr PI, Casper TC, et al. Lactobacillus rhamnosus GG versus placebo for acute gastroenteritis in children. N Engl J Med 2018; 379: 2002–2014.
- 7.Gutiérrez Castrellón P, Polanco Allué I, Salazar Lindo E. An evidence based Iberic-Latin American guideline for acute gastroenteritis management in infants and prescholars. An Pediatr (Barc) 2010; 72: 220.e1–220.e20.
- 8.Eberlin M, Mück T, Michel MC. A comprehensive review of the pharmacodynamics, pharmacokinetics, and clinical effects of the neutral endopeptidase inhibitor racecadotril. Front Pharmacol 2012; 3: 93.
- 9.Takeda Y, Inaba S, Furukawa K, et al. Effects of chronic neutral endopeptidase inhibition in rats with cyclosporine-induced hypertension. J Hypertens 2000; 18: 927–933.
- 10.Bralet J, Mossiat C, Lecomte JM, et al. Diuretic and natriuretic responses in rats treated with enkephalinase inhibitors. Eur J Pharmacol 1990; 179: 57–64.
- 11.Favrat B, Burnier M, Nussberger J, et al. Neutral endopeptidase versus angiotensin converting enzyme inhibition in essential hypertension. J Hypertens 1995; 13: 797–804.
- 12.Schwartz JC. Racecadotril: a new approach to the treatment of diarrhoea. Int J Antimicrob Agents 2000; 14: 75–79.
- 13.Farthing MJ. Novel targets for the pharmacotherapy of diarrhoea: a view for the millennium. J Gastroenterol Hepatol 2000; 15: (Suppl): G38–G45.
- 14.Gordon M, Akobeng A. Racecadotril for acute diarrhoea in children: systematic review and meta-analyses. Arch Dis Child 2016; 101: 234–240.
- 15.Santos M, Marañón R, Miguez C, et al. Use of racecadotril as outpatient treatment for acute gastroenteritis: a prospective, randomized, parallel study. J Pediatr 2009; 155: 62–67.
- 16.Eberlin M, Chen M, Mueck T, et al. Racecadotril in the treatment of acute diarrhea in children: a systematic, comprehensive review and meta-analysis of randomized controlled trials. BMC Pediatr 2018; 18: 124.
- 17.Turck D, Berard H, Fretault N, et al. Comparison of racecadotril and loperamide in children with acute diarrhoea. Aliment Pharmacol Ther 1999; 13: (Suppl 6): 27–32.
- 18.Florez ID, Veroniki AA, Al Khalifah R, et al. Comparative effectiveness and safety of interventions for acute diarrhea and gastroenteritis in children: a systematic review and network meta-analysis. PLoS One 2018; 13: e0207701.
- 19.Tran LC, Lazonby G, Ellis D, et al. Racecadotril may reduce diarrhoea in microvillous inclusion disease. J Pediatr Gastroenterol Nutr 2017; 64: e25–e26.
- 20.Baumer P. Proposal for the inclusion of racecadotril in the who model list of essential medicines. http://archives.who.int/eml/expcom/children/Applications/racecadotril/Proposal_racecadotril.pdf. Published May 2007. Accessed 5 November 2019.
- 21.Rautenberg TA, Zerwes U, Lee WS. Cost utility, budget impact, and scenario analysis of racecadotril in addition to oral rehydration for acute diarrhea in children in Malaysia. Clinicoecon Outcomes Res 2018; 10: 169–178.
- 22.Rautenberg TA, Zerwes U. The cost utility and budget impact of adjuvant racecadotril for acute diarrhea in children in Thailand. Clinicoecon Outcomes Res 2017; 9: 411–422.
- 23.Rautenberg TA, Zerwes U, Foerster D, et al. Evaluating the cost utility of racecadotril for the treatment of acute watery diarrhea in children: the RAWD model. Clinicoecon Outcomes Res 2012; 4: 109–116.
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