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Prospective randomized double-blind trial of racecadotril compared with loperamide in elderly people with gastroenteritis living in nursing homes

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Abstract

Aim

Our aim was to compare the efficacy and tolerability of loperamide and racecadotril in elderly patients with acute diarrhea.

Research design and methods

We performed a randomized, prospective, double-blind, and parallel group design implemented in geriatric nursing homes in Catanzaro, Italy, from February 2008 to March 2009. Patients of both sexes were randomly allocated to receive either one tablet of racecadotril 100 mg every 8 h or two tablets of loperamide 2.0 mg followed by one tablet after each unformed stool, up to four tablets in any 24-h period. Patients were treated until recovery, defined as the production of two consecutive normal stools or no stool production for a period of 12 h.

Results

Normal stools were collected 36 ± 4 h after the beginning of racecadotril and in 63 ± 6 h from the beginning of loperamide administration (P < 0.01). The median time of abdominal pain in the intent-to-treat (ITT) population was 14 h for racecadotril and 28 h for loperamide. In the per-protocol (PP) population, the median time of abdominal pain was 14 h for racecadotril and 32 h for loperamide (P < 0.01). About the 50% of patients experienced at least one adverse event during the study: 12% in the racecadotril group and 60% in the loperamide group. The most frequently occurring adverse events were nausea and constipation. Genetic analysis did not report the presence of rapid or poor metabolizers. Pharmacoeconomic analysis performed at the end of our study documented an increase in costs in the loperamide group with respect to the racecadotril group (P < 0.01).

Conclusions

Racecadotril is more effective than loperamide−probably due to drug interaction with loperamide−and it is not related to pharmacogenetic susceptibility. Racecadotril is also more cost effective than loperamide.

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References

  1. Aranda-Michel J, Giannella RA (1999) Acute diarrhea: a practical review. Am J Med 106:670–676. doi:10.1016/S0002-9343(99)00128-X PMID 10378626

    Article  CAS  PubMed  Google Scholar 

  2. Frenzen PD (2003) Mortality due to gastroenteritis of unknown etiology in the United States. J Infect Dis 187:441–452. doi:10.1086/368097 PMID: 12552428

    Article  PubMed  Google Scholar 

  3. Hunter KF, Cyr D (2006) Pharmacotherapeutics in older adults. J Wound Ostomy Continence Nurs 33:630–636 PMID: 17108773

    PubMed  Google Scholar 

  4. Shaojun S, Morike K, Klotz U (2008) The clinical implications of ageing for rational drug therapy. Eur J Clin Pharmacol 64:183–189 PMID: 9782630

    Article  Google Scholar 

  5. Evans HS, Madden P, Douglas C, Adak GK, O'Brien SJ, Djuretic T, Wall PG, Stanwell-Smith R (1998) General outbreak of infectious disease in England and Wales: 1995 and 1996. Commun Dis Public Health 1:165–171 PMID: 9782630

    CAS  PubMed  Google Scholar 

  6. Edmonson LM, Ebbert JO, Evans JM (2000) Report of a rotavirus outbreak in an adult nursing home population. J Am Med Dir Assoc 1:175–179 PMID: 12816557

    CAS  PubMed  Google Scholar 

  7. Huh JW, Kim WH, Moon SG, Lee JB, Lim YH (2009) Viral etiology and incidence associated with acute gastroenteritis in a 5-year survey in Gyeonggi province, South Korea. J Clin Virol 44:152–156. doi:10.1016/j.jcv.2008.11.016 PMID: 19131274

    Article  PubMed  Google Scholar 

  8. Nilsson M, Svenungsson B, Hedlund K-O, Uhnoo I, Lagergren A, Akre T, Svensson L (2000) Incidence and genetic diversity of group c rotavirus among adults. J Infect Dis 182:687–684. doi:10.1086/315772 PMID: 10950759

    Article  Google Scholar 

  9. Kosek M, Bern C, Guerrant RL (2003) The global burden of diarrhoeal disease, as estimated from studies published between 1992 and 2000. Bull World Health Organ 81:197–204. doi:10.1590/S0042-96862003000300010 PMID: 12764516

    PubMed  Google Scholar 

  10. Bennett RG, Greenough WB 3rd (1993) Approach to acute diarrhea in the elderly. Gastroenterol Clin North Am 22:517–533 PMID: 8406728

    CAS  PubMed  Google Scholar 

  11. Slotwiner-Nie PK, Brandt LJ (2001) Infectious diarrhea in the elderly. Gastroenterol Clin North Am 30:625–635 PMID: 11586549

    Article  CAS  PubMed  Google Scholar 

  12. Trinh C, Prabhakar K (2007) Diarrheal diseases in the elderly. Clin Geriatr Med 23:833–856. doi:10.1016/j.cger.2007.06.005 PMID: 17923341

    Article  PubMed  Google Scholar 

  13. Shahbazian A, Heinemann A, Schmidhammer H, Beubler E, Holzer-Petsche U, Holzer P (2002) Involvement of mu- and kappa-, but not delta-, opioid receptors in the peristaltic motor depression caused by endogenous and exogenous opioids in the guinea-pig intestine. Br J Pharmacol 135:741–750. doi:10.1038/sj.bjp.0704527 PMID: 11834622

    Article  CAS  PubMed  Google Scholar 

  14. Huijghebaert S, Awouters F, Tytgat GNJ (2003) Racecadotril versus loperamide: antidiarrheal research revisited. Dig Dis Sci 48:239–250. doi:10.1023/A:1021989606317 PMID: 12643598

    Article  Google Scholar 

  15. Prado D, Global Adult Racecadotril Study Group (2002) A multinational comparison of racecadotril and loperamide in the treatment of acute watery diarrhoea in adults. Scand J Gastroenterol 37:656–661 PMID: 12126242

    Article  CAS  PubMed  Google Scholar 

  16. Bergmann JF, Chaussade S, Couturier D, Baumer P, Schwartz JC, Lecomte JM (1992) Effects of acetorphan, an antidiarrhoeal enkephalinase inhibitor, on oro-caecal and colonic transit times in healthy volunteers. Aliment Pharmacol Ther 6:305–313 PMID: 1350927

    CAS  PubMed  Google Scholar 

  17. Guerrant RL, Bobak DA (1991) Bacterial and protozoal gastroenteritis. N Engl J Med 325:327–340 PMID: 2057037

    Article  CAS  PubMed  Google Scholar 

  18. Blacklow NR, Greenberg HB (1991) Viral gastroenteritis. N Engl J Med 325:252–264 PMID: 1647494

    CAS  PubMed  Google Scholar 

  19. de Wit MA, Koopmans MP, Kortbeek LM, Wannet WJ, Vinjé J, van Leusden F, Bartelds AI, van Duynhoven YT (2001) Sensor, a population-based cohort study on gastroenteritis in the Netherlands: incidence and etiology. Am J Epidemiol 154(7):666–674

    Article  PubMed  Google Scholar 

  20. DuPont HL (2005) What’s new in enteric infectious diseases at home and abroad. Curr Opin Infect Dis 18:407–412 PMID: 16148527

    Article  PubMed  Google Scholar 

  21. Marsella M, Raimondi L, Bergamini M, Sprocati M, Bigi E, De Sanctis V, Borgna-Pignatti C, Gabutti G (2009) Epidemiology of rotavirus-associated hospital admissions in the province of Ferrara, Italy. Eur J Pediatr. [PMID: 19255784]

  22. Chadwick PR, McCann R (1994) Transmission of a small round structured virus by vomiting during a hospital outbreak of gastroenteritis. J Hosp Infect 26:251–259 PMID: 7915285

    Article  CAS  PubMed  Google Scholar 

  23. Parashar U, Quiroz ES, Mounts AW, Monroe SS, Fankhauser RL, Ando T, Noel JS, Bulens SN, Beard SR, Li JF, Bresee JS, Glass RI (2001) “Norwalk-like viruses”. Public health consequences and outbreak management. MMWR Recomm Rep 50:1–17

    CAS  PubMed  Google Scholar 

  24. Said MA, Perl TM, Sears CL (2008) Healthcare epidemiology: gastrointestinal flu: norovirus in health care and long-term care facilities. Clin Infect Dis 47:1202–1208. doi:10.1086/592299 PMID: 18808354

    Article  PubMed  Google Scholar 

  25. Cheesbrough JS, Green J, Gallimore CI, Wright PA, Brown DW (2000) Widespread environmental contamination with Norwalk-like viruses (NLV) detected in a prolonged hotel outbreak of gastroenteritis. Epidemiol Infect 125:93–98 PMID: 11057964

    Article  CAS  PubMed  Google Scholar 

  26. Jiang ZD, Lowe B, Verenkar MP, Ashley D, Steffen R, Tornieporth N, von Sonnenburg F, Waiyaki P, DuPont HL (2002) Prevalence of enteric pathogens among international travelers with diarrhea acquired in Kenya (Mombasa), India (Goa), or Jamaica (Montego Bay). J Infect Dis 185:497–502

    Article  PubMed  Google Scholar 

  27. Wang HH, Shieh MJ, Liao KF (2005) A blind, randomized comparison of racecadotril and loperamide for stopping acute diarrhea in adults. World J Gastroenterol 11:1540–1543 PMID: 15770734

    CAS  PubMed  Google Scholar 

  28. Rachmilewitz D, Karmeli F, Chorev M, Selinger Z (1983) Effect of opiates on human colonic adenylate cyclase activity. Eur J Pharmacol 93:169–173 PMID: 6580173

    Article  CAS  PubMed  Google Scholar 

  29. Shook JE, Lemcke PK, Gehrig CA, Hruby VJ, Burks TF (1989) Antidiarrhoeal properties of supraspinal mu and delta and peripheral mu, delta and kappa opioid receptor: Inhibition of diarrhea without constipation. J Pharmacol Exp Ther 249:83–90 PMID: 2540324

    CAS  PubMed  Google Scholar 

  30. Cézard JP, Duhamel JF, Meyer M (1996) Efficacy and tolerance of acetorphan in infant acute diarrhea: a multicentric, double blind study. Gastroenterology 110(Suppl):A795 Abstract

    Google Scholar 

  31. Salazar-Lindo E, Santisteban-Ponce J, Chea-Woo E, Gutierrez M (2000) Racecadotril in the treatment of acute watery diarrhea in children. N Engl J Med 343:463–467 PMID: 10944563

    Article  CAS  PubMed  Google Scholar 

  32. Hamza H, Ben Khalifa H, Baumer P, Berard H, Lecomte JM (1999) Racecadotril versus placebo in the treatment of acute diarrhoea in adults. Aliment Pharmacol Ther 13(Suppl 6):15–19 PMID: 10646047

    CAS  PubMed  Google Scholar 

  33. Vetel JM, Berard H, Fretault N, Lecomte JM (1999) Comparison of racecadotril and loperamide in adults with acute diarrhoea. Aliment Pharmacol Ther 13(Suppl 6):21–26 PMID: 10646048

    CAS  PubMed  Google Scholar 

  34. Rouge J, Baumer P, Berard H, Schwartz JC, Lecomte JM (1993) The enkephalinase inhibitor, acetorphan, in acute diarrhea: a double-blind control clinical trial versus loperamide. Scand J Gastroenterol 28:352–354 PMID 8488368

    Article  Google Scholar 

  35. Basilisco G, Camboni G, Bozzani A, Paravicini M, Bianchi PA (1987) Oral naloxone antagonizes loperamide-induced delay of orocecal transit. Dig Dis Sci 32:829–832 PMID: 3608730

    Article  CAS  PubMed  Google Scholar 

  36. Riddle MS, Arnold S, Tribble DR (2008) Effect of adjunctive loperamide in combination with antibiotics on treatment outcomes in traveler's diarrhea: a systematic review and meta-analysis. Clin Infect Dis 47:1007–1014. doi:10.1086/591703 PMID: 18781873

    Article  CAS  PubMed  Google Scholar 

  37. Miyazaki H, Nambu K, Matsunaga Y, Hashimoto M (1979) Disposition and metabolism of [14C]loperamide in rats. Eur J Drug Metab Pharmacokinet 4:199–206 PMID: 535599

    Article  CAS  PubMed  Google Scholar 

  38. Yoshida K, Nambu K, Arakawa S, Miyazaki H, Hashimoto M (1979) Metabolites of loperamide in rats. Biomed Mass Spectrom 6:253–259 PMID: 476289

    Article  CAS  PubMed  Google Scholar 

  39. He H, Sadeque A, Erve JC, Wood AJ, Hachey DL (2000) Quantitation of loperamide and N-demethyl-loperamide in human plasma using electrospray ionization with selected reaction ion monitoring liquid chromatography-mass spectrometry. J Chromatogr B Biomed Sci Appl 744:323–331 PMID: 10993521

    Article  CAS  PubMed  Google Scholar 

  40. Tayrouz Y, Ganssmann B, Ding R, Klingmann A, Aderjan R, Burhenne J, Haefeli WE, Mikus G (2001) Ritonavir increases loperamide plasma concentrations without evidence for P-glycoprotein. involvement. Clin Pharmacol Ther 70:405–414

    Article  CAS  PubMed  Google Scholar 

  41. Kim KA, Chung J, Jung DH, Park JY (2004) Identification of cytochrome P450 isoforms involved in the metabolism of loperamide in human liver microsomes. Eur J Clin Pharmacol 60:575–581. doi:10.1007/s00228-004-0815-3 PMID: 15365656

    Article  CAS  PubMed  Google Scholar 

  42. Lecomte JM, Costentin J, Vlaiculescu A, Chailet P, Marcais-Collado H, Llorens-Cortes C, Leboyer M, Schwartz JC (1986) Pharmacological properties of acetorphan, a parenterally active enkephalinases inhibitor. J Pharmacol Exp Ther 237:937–944 PMID: 3519939

    CAS  PubMed  Google Scholar 

  43. Pirmohamed M, James S, Meakin S, Green C, Scott AK, Walley TJ, Farrar K, Park BK, Breckenridge AM (2004) Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ 329:15–19 PMID: 15231615

    Article  PubMed  Google Scholar 

  44. Beijer HJ, de Blaey CJ (2002) Hospitalizations caused by adverse drug reactions (ADR): a meta-analysis of observational studies. Pharm World Sci 24:46–54 PMID: 12061133

    Article  CAS  PubMed  Google Scholar 

  45. Gallelli L, Colosimo M, Pirritano D, Ferraro M, De Fazio S, Marigliano NM, De Sarro G (2007) Retrospective evaluation of adverse drug reactions induced by nonsteroidal anti-inflammatory drugs. Clin Drug Investig 27:115–122 PMID: 17217316

    Article  CAS  PubMed  Google Scholar 

  46. Gallelli L, Ferreri G, Colosimo M, Pirritano D, Guadagnino L, Pelaia G, Maselli R, De Sarro GB (2002) Adverse drug reactions to antibiotics observed in two pulmonology divisions of Catanzaro, Italy: a six-year retrospective study. Pharmacol Res 46:395–400. doi:10.1016/S1043661802002104 PMID: 12419643

    Article  CAS  PubMed  Google Scholar 

  47. Gallelli L, Ferreri G, Colosimo M, Pirritano D, Flocco MA, Pelaia G, Maselli R, De Sarro GB (2003) Retrospective analysis of adverse drug reactions to bronchodilators observed in two pulmonary divisions of Catanzaro, Italy. Pharmacol Res 47:493–499. doi:10.1016/S1043-6618(03)00003-3 PMID: 12742002

    Article  CAS  PubMed  Google Scholar 

  48. Gallelli L, Nardi M, Prantera T, Barbera S, Raffaele M, Arminio D, Pirritano D, Colosimo M, Maselli R, Pelaia G, De Gregorio P, De Sarro GB (2004) Retrospective analysis of adverse drug reactions induced by gemcitabine treatment in patients with non-small cell lung cancer. Pharmacol Res 49:259–263. doi:10.1016/j.phrs.2003.10.001 PMID: 14726222

    Article  CAS  PubMed  Google Scholar 

  49. Zhang M, Holman CD, Price SD, Sanfilippo FM, Preen DB, Bulsara MK (2009) Comorbidity and repeat admission to hospital for adverse drug reactions in older adults: retrospective cohort study. BMJ 338:a2752. doi:10.1136/bmj.a2752 PMID: 19129307

    Article  PubMed  Google Scholar 

  50. Schiller LR, Santa Ana CA, Morawski SG, Fordtran JS (1984) Mechanism of the antidiarrheal effect of loperamide. Gastroenterology 86:1475–1480 PMID: 6714575

    CAS  PubMed  Google Scholar 

  51. Kachel G, Ruppin H, Hagel J, Barina W, Meinhardt M, Domschke W (1986) Human intestinal motor activity and transport: effects of a synthetic opiate. Gastroenterology 90:85–93 PMID: 3940260

    CAS  PubMed  Google Scholar 

  52. Sninsky CA, Davis RH, Clench MH, Thomas KD, Mathias JR (1986) Effect of lidamidine hydrochloride and loperamide on gastric emptying and transit of the small intestine: a double-blind study. Gastroenterology 90:68–73 PMID: 3940258

    CAS  PubMed  Google Scholar 

  53. De Fazio S, Gallelli L, De Siena A, De Sarro G, Scordo MG (2008) Role of CYP3A5 in abnormal clearance of methadone. Ann Pharmacother 42:893–897 PMID: 18460585

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Chair of Pharmacology, School of Medicine and Surgery, Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Mater Domini University Hospital, Catanzaro, Italy

    Luca Gallelli, Grazia A. Tolotta, Pierandrea Rende, Norma M. Marigliano & Giovambattista De Sarro

  2. Geriatric Nursing Home “Madonna di Porto”, Catanzaro, Italy

    Manuela Colosimo, Francesca Mazzei & Norma M. Marigliano

  3. Chair of Molecular Biology, School of Medicine and Surgery Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Mater Domini University Hospital, Catanzaro, Italy

    Daniella Falcone & Lucia S. Curto

  4. Chair of Biochemistry, School of Medicine and Surgery Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Mater Domini University Hospital, Catanzaro, Italy

    Laura Luberto

  5. Department of Pediatrics, Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Rome, Italy

    Salvatore Cucchiara

  6. School of Medicine and Surgery Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Clinical Pharmacology Unit, Mater Domini University Hospital, Viale Europa–Germaneto, 88100, Catanzaro, Italy

    Luca Gallelli

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  1. Luca Gallelli
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Correspondence to Luca Gallelli.

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Gallelli, L., Colosimo, M., Tolotta, G.A. et al. Prospective randomized double-blind trial of racecadotril compared with loperamide in elderly people with gastroenteritis living in nursing homes. Eur J Clin Pharmacol 66, 137–144 (2010). https://doi.org/10.1007/s00228-009-0751-3

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