DOCSLIB.ORG

Systematic Literature Review and Indirect Treatment Comparison Of

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Systematic Literature Review and Indirect Treatment Comparison Of PGI8 Systematic literature review and indirect treatment comparison of linaclotide versus other oral constipation treatments in patients with chronic constipation H Okumura,1 W Tang,2 K Iwasaki,2 S Shoji,1 T Odaka,3 A Nakajima4 1Astellas Pharma Inc., Tokyo, Japan; 2Milliman Inc., Tokyo, Japan; 3Odaka Medical and Gastrointestinal Clinic, Chiba, Japan; 4Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan INTRODUCTION Figure 2. Treatments included in NMA. Figure 3. Risk of bias of included trials. ● Chronic constipation (CC), including functional constipation, irritable bowel CC Naloxegol 12.5Naloxegol mg 5 mg IBS-C syndrome with constipation (IBS-C), and opioid-induced constipation (OIC), Naloxegol 25 mg OIC [12w] [4w] [12w] 1 Naloxegol[4w, 50 12w] mg [12w] [3w, 12w] CC and IBS-C negatively affects patients’ quality of life and has a prevalence rate of [3w, 12w]Alvimopan 0.5 mg [12w] Random sequence generation Alvimopan 1 mg Methylnaltrexone 450 mg 2,3 [4w] Methylnaltrexone 300 mg CC and OIC (selection bias) approximately 14% and 28% worldwide and in Japan, respectively. Methylnaltrexone 150 mg Lactitol[2w] 20 g Naloxone 2.5 mg Lactitol[7d] 10 g Allocation concealment ● The most commonly recommended treatments are polyethylene glycol [3w] Wheat (triticum) 20 g (selection bias) Naloxone 5 mg [4w] (PEG), lubiprostone, linaclotide, prucalopride, lactulose, bisacodyl, and [3w] Naloxone 10 mg Ispaghula 20 g 4 [4w] Blinding of participants and personnel [3w] Ispaghula 10.8 g dietary fibre ; in Japan, magnesium oxide followed by stimulant laxatives Naloxone 20 mg [14d] (performance bias) [3w] 5 Bisacodyl 10 mg are commonly used. Tegaserod 4 mg [3d, 4w] [12w] Tegaserod 12 mg Lactulose 20 g Blinding of outcome assessment ● Linaclotide, a first-in-class, minimally absorbed oligo peptide with guanylate [4w, 12w] [2w, 3w, 4w] (detection bias) Lactulose 10 g cyclase-C agonistic activity, is approved for chronic idiopathic constipation Placebo [7d, 3w] Prucalopride 4 mg Incomplete outcome data 6 [4w] (72 μg and 145 μg) and IBS-C (290 μg) in the United States and for CC and Prucalopride 2 mg (attrition bias) 7 [4w] IBS-C in Japan (500 µg). [2w, 2m] Prucalopride 1 mg Linaclotide 62.5 μg [4w] Selective reporting PEG 26 g (reporting bias) ● Most treatments for CC have limited efficacy and are associated with Linaclotide[4w, 12w]72/75 μg [4w] PEG 20 g 8 Linaclotide[5d, 2w] 100 μg [4w] unwanted side effects. Moreover, selection of the most appropriate PEG 11.8 g Linaclotide[2w, 2m] 125 μg Other bias therapeutic option is limited by a lack of direct comparisons between PEG 10/10.35[4w] g PEG 5.9 g [4w, 12w] [4w] the available drug classes. Linaclotide 133/145/150Linaclotide[2w, 2m] μg250 μg Plecanatide[4w] 6 mg Plecanatide 3 mg 0% 25% 50% 75% 100% [4w, 12w] [12w] ● A recently conducted network meta-analysis (NMA) showed that most Linaclotide 266/290/300Linaclotide[2w, 12w, μg500 2m] μg [12w] [4w, 12w] [5d] LinaclotideLinaclotide 579/600 μg 1000 μg pharmacological therapies for functional constipation have similar efficacy; [1w, 2m] [1w] Lubiprostone 16 µg Lubiprostone 48 µg however, this meta-analysis did not include patients with IBS-C.9 Lubiprostone 32[1w, µg 2w, 4w, 12w] Low risk of bias Unclear risk of bias High risk of bias The nodes represent the treatment modalities compared and the lines represent the comparison arms in each trial analysed. The size of each node represents the number of patients pooled for each treatment and the thickness of the lines represents the number of trials for each comparison. CC, chronic constipation; d, days; IBS-C, inflammatory bowel syndrome with constipation; m, months; OIC, opioid-induced OBJECTIVE constipation; w, weeks. Primary objective ● To compare the efficacy of linaclotide with other medications for CC, ● A total of 47 treatments/16 drugs (different doses of the same drug were ● After screening, selected trials were assessed for risk of bias using the including functional constipation, IBS-C, and OIC, by conducting a defined as separate treatments), including placebo, were included in the NMA. Cochrane’s Risk of Bias Tool; 4 trials had at least 1 domain for high risk systematic literature review and NMA. Treatment duration ranged from 3 days to 12 weeks (Figure 2). of bias (Figure 3). METHODS RESULTS Table 1. Study design highlights. ● In terms of the change in weekly spontaneous bowel movements (SBM; Figure 4), the approved dose of linaclotide 500 µg in Japan was statistically significantly more effective (mean difference, 95% credible interval [CI]) than placebo (-1.906; 95% CI, -2.672 to -1.197), lubiprostone 16 µg (-1.903; -3.254 to -0.704), Study design ● Systematic literature review and NMA of randomized trials of 43 oral drugs approved for CC methylnaltrexone 150 mg (-1.805; -3.207 to -0.397), methylnaltrexone 300 mg (-1.413; -2.771 to -0.016), methylnaltrexone 450 mg (-1.407; -2.796 to -0.003), ● The trials for analysis included those conducted globally and naloxegol 12.5 mg (-1.322; -2.403 to -0.240), tegaserod 4 mg (-1.148; -2.139 to -0.172), and tegaserod 12 mg (-1.023; -1.909 to -0.182). in Japan ● Linaclotide 500 µg was statistically significantly less effective than the non-approved dose of linaclotide 600 µg (1.156; 0.025-2.281) and bisacodyl 10 mg (2.997; Databases searched ● PubMed, Cochrane CENTRAL, and ClinicalTrials.gov 1.652-4.359). ● Ichushi-web (database of Japanese medical studies maintained by the Japan Medical Abstracts Society) ● Sensitivity analyses showed that findings for linaclotide 500 µg were generally consistent when the following trials were excluded: IBS-C and OIC Figure( 5), and clinical trials of linaclotide in Japan and mild-to-moderate constipation (Figure 6). Eligibility criteria ● All approved oral drugs identified from WHO Anatomical Therapeutic Chemical classification system, World Figure 4. Overall mean difference in the number Figure 5. Sensitivity analysis: 26 trials of patients Figure 6. Sensitivity analysis: 30 trials of patients Gastroenterology Organization Global Guidelines, and of weekly SBM before and after treatment with CC (IBS-C and OIC were excluded). with average baseline SBM <3 (mild-to-moderate Japanese guidelines for the treatment of constipation compared with linaclotide 500 µg. constipation was excluded). ● Patients with CC, including IBS-C and OIC ● Controlled clinical trials (randomized and quasi-randomized) Constipation Patients Constipation Patients Constipation Patients treatments (n) treatments (n) treatments (n) ● Patients with constipation due to organic disease and observational studies were excluded Placebo 8692 Placebo 3838 Linaclotide 500 µg 511 Linaclotide 500 µg 164 Placebo 4340 Linaclotide 62.5 µg 181 Linaclotide 62.5 µg 78 Linaclotide 500 µg 511 Efficacy endpoint ● Change from baseline in weekly number of SBM was Linaclotide 72/75 µg 603 Linaclotide 72/75 µg 524 Linaclotide 62.5 µg 181 Linaclotide 100 µg 24 Linaclotide 100 µg 12 Linaclotide 72/75 µg 470 Linaclotide 125 µg 172 Linaclotide 125 µg 69 Linaclotide 100 µg analysed Linaclotide 133/145/150 µg 772 Linaclotide 133/145/150 µg 690 Linaclotide 125 µg 172 Linaclotide 250 µg 175 Linaclotide 250 µg 72 Linaclotide 133/145/150 µg 639 ● Mean differences of SBM were compared between linaclotide Linaclotide 266/290/300 µg 2004 Linaclotide 266/290/300 µg 697 Linaclotide 250 µg 175 Linaclotide 579/600 µg 202 Linaclotide 579/600 µg 113 Linaclotide 266/290/300 µg 1040 500 µg (standard dose in Japan) and other treatments Linaclotide 1000 µg 12 Linaclotide 1000 µg Linaclotide 579/600 µg 62 Linaclotide 1000 µg Lubiprostone 16 µg 431 Lubiprostone 16 µg 41 ● Mean difference and 95% credible intervals for SBM were Lubiprostone 16 µg Lubiprostone 32 µg 43 Lubiprostone 32 µg 43 Lubiprostone 32 µg Lubiprostone 48 µg 1200 Lubiprostone 48 µg 416 Lubiprostone 48 µg 550 calculated by analysing the probability of each drug having Placanatide 3 mg 453 Placanatide 3 mg 453 Placanatide 3 mg 453 Placanatide 6 mg 441 the best outcome (increased SBM) Placanatide 6 mg 441 Placanatide 6 mg 441 PEG 5.9 g 67 PEG 5.9 g PEG 5.9 g 67 PEG 10/10.35 g 86 PEG 10/10.35 g PEG 10/10.35 g 86 PEG 11.8 g 69 PEG 11.8 g PEG 11.8 g 69 NMA method ● Multivariate, random-effects meta-analysis based on the PEG 20 g 99 PEG 20 g PEG 20 g 67 PEG 26 g 10 PEG 26 g 67 PEG 26 g 67 methodology proposed by White et al. (2012) using Bayesian Prucalopride 1 mg 113 Prucalopride 1 mg 113 Prucalopride 1 mg Prucalopride 2 mg 141 Prucalopride 2 mg 75 Prucalopride 2 mg 66 modelling Prucalopride 4 mg 143 Prucalopride 4 mg 79 Prucalopride 4 mg 64 Lactulose 10 g 165 Lactulose 10 g Lactulose 10 g Lactulose 20 g 152 Lactulose 20 g Lactulose 20 g Bisacodyl 10 mg 274 Bisacodyl 10 mg 274 Bisacodyl 10 mg Sensitivity analysis ● Limited to CC Ispaghula 10.8 g 91 Ispaghula 10.8 g 91 Ispaghula 10.8 g 91 Ispaghula 20 g 10 Ispaghula 20 g 10 Ispaghula 20 g 10 for NMA ● Limited to trials with average baseline weekly SBM <3 Wheat (triticum) 20 g 12 Wheat (triticum) 20 g 12 Wheat (triticum) 20 g 12 Lactitol 10 g 63 Lactitol 10 g Lactitol 10 g Lactitol 20 g 30 Lactitol 20 g Lactitol 20 g CC, chronic constipation; IBS-C, irritable bowel syndrome with constipation; NMA, network meta-analysis; OIC, opioid-induced Methylnaltrexone 150 mg 201 Methylnaltrexone 150 mg Methylnaltrexone 150 mg 201 Methylnaltrexone 300 mg 201 Methylnaltrexone 300 mg Methylnaltrexone 300 mg 201 constipation; SBM, spontaneous bowel movements; WHO, World Health Organization.
Load more

Recommended publications
  • Constipation: a Parent's Guide
    CONSTIPATION: A PARENT’S GUIDE Twenty Questions About Constipation: Answers to Guide Parents and Professionals Constipation is the abnormally delayed or infrequent passage of hard stools. Most children, and many adults, too, become constipated from time to time. Often, the duration is short; occasionally it persists for months, even years. Although constipation can be uncomfortable, may create worry, and sometimes seem serious, fortunately it does not have long-term, troubling effects in most healthy children. This Booklet is designed to help you deal with childhood constipation by answering several questions and outlining management instructions for you to follow. Questions answered are: 1. What are the normal 11. What can we learn from patterns of bowel physical exam results? movements at 12. What is our treatment different ages? program for constipation? 2. What makes up bowel 13. How is the colon movements and how do cleaned out? they travel? 14. How are stools softened? 3. What is constipation? 15. Why is trying to have 4. When is constipation most bowel movements twice likely to occur? a day so important? 5. Why does constipation 16. What are the expected persist in some children? results of the treatment 6. Why would a child hold program? back stool and what 17. What do we do if the happens then? cleansing regimen is 7. How can proper toilet not successful? training help? 18. What is the long-term 8. Why would stool back up program for children in the colon? prone to constipation? 9. Why do some children 19. Does a special diet help have soiling accidents? resolve constipation? 10.
    [Show full text]
  • The American Society of Colon and Rectal Surgeons' Clinical Practice
    CLINICAL PRACTICE GUIDELINES The American Society of Colon and Rectal Surgeons’ Clinical Practice Guideline for the Evaluation and Management of Constipation Ian M. Paquette, M.D. • Madhulika Varma, M.D. • Charles Ternent, M.D. Genevieve Melton-Meaux, M.D. • Janice F. Rafferty, M.D. • Daniel Feingold, M.D. Scott R. Steele, M.D. he American Society of Colon and Rectal Surgeons for functional constipation include at least 2 of the fol- is dedicated to assuring high-quality patient care lowing symptoms during ≥25% of defecations: straining, Tby advancing the science, prevention, and manage- lumpy or hard stools, sensation of incomplete evacuation, ment of disorders and diseases of the colon, rectum, and sensation of anorectal obstruction or blockage, relying on anus. The Clinical Practice Guidelines Committee is com- manual maneuvers to promote defecation, and having less posed of Society members who are chosen because they than 3 unassisted bowel movements per week.7,8 These cri- XXX have demonstrated expertise in the specialty of colon and teria include constipation related to the 3 common sub- rectal surgery. This committee was created to lead inter- types: colonic inertia or slow transit constipation, normal national efforts in defining quality care for conditions re- transit constipation, and pelvic floor or defecation dys- lated to the colon, rectum, and anus. This is accompanied function. However, in reality, many patients demonstrate by developing Clinical Practice Guidelines based on the symptoms attributable to more than 1 constipation sub- best available evidence. These guidelines are inclusive and type and to constipation-predominant IBS, as well. The not prescriptive.
    [Show full text]
  • Anorectal Disorders Satish S
    Gastroenterology 2016;150:1430–1442 Anorectal Disorders Satish S. C. Rao,1 Adil E. Bharucha,2 Giuseppe Chiarioni,3,4 Richelle Felt-Bersma,5 Charles Knowles,6 Allison Malcolm,7 and Arnold Wald8 1Division of Gastroenterology and Hepatology, Augusta University, Augusta, Georgia; 2Department of Gastroenterology and Hepatology, Mayo College of Medicine, Rochester, Minnesota; 3Division of Gastroenterology of the University of Verona, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy; 4Division of Gastroenterology and Hepatology and UNC Center for Functional GI and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; 5Department of Gastroenterology/Hepatology, VU Medical Center, Amsterdam, The Netherlands; 6National Centre for Bowel Research and Surgical Innovation, Blizard Institute, Queen Mary University of London, London, United Kingdom; 7Division of Gastroenterology, Royal North Shore Hospital, and University of Sydney, Sydney, Australia; 8Division of Gastroenterology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin This report defines criteria and reviews the epidemiology, questionnaires and bowel diaries are correlated,5 some pathophysiology, and management of the following com- patients may not accurately recall bowel symptoms6; hence, mon anorectal disorders: fecal incontinence (FI), func- symptom diaries may be more reliable. tional anorectal pain, and functional defecation disorders. In this report, we examine the prevalence and patho- FI is defined as the recurrent uncontrolled passage of fecal physiology of anorectal disorders, listed in Table 1,and material for at least 3 months. The clinical features of FI provide recommendations for diagnostic evaluation and are useful for guiding diagnostic testing and therapy. management. These supplement practice guidelines rec- ANORECTAL Anorectal manometry and imaging are useful for evalu- ommended by the American Gastroenterological Associa- fl ating anal and pelvic oor structure and function.
    [Show full text]
  • Peptide Therapeutics Designing a Science-Led Strategic Quality Control Program
    BioProcess International Peptide SPECIAL REPORT Therapeutics Designing a Science-Led Strategic Quality Control Program INTERTEK PHARMACEUTICAL SERVICES Your partner for regulatory-driven, phase appropriate analytical programs tailored to your molecule. Our experts help you to navigate the challenges of development, regulatory submission, and manufacturing. Peptide Therapeutics Designing a Science-Led Strategic Quality Control Program Shashank Sharma and Hannah Lee ince the emergence of peptide therapeutics in the 1920s with the advent of insulin therapy, the market for this product class has continued to expand with global revenues anticipatedS to surpass US$50 billion by 2024 (1). The growth of peptide therapeutics is attributed not only to improvements in manufacturing, but also to a rise in demand because of an increasingly aging population that is driving an increase in the occurrence of long-term diseases. The need for efficient and low-cost drugs and rising investments in research and development of novel drugs continues to boost market growth and fuel the emergence of generic versions that offer patients access to vital medicines at low costs. North America has been the dominant market for peptide therapeutics, with the Asia–Pacific region Insulin molecular model; the first therapeutic expected to grow at a faster rate. The global peptides use of this peptide hormone was in the market has attracted the attention of key players 1920s to treat diabetic patients. within the pharmaceutical industry, including Teva Pharmaceuticals, Eli Lilly, Novo Nordisk, Pfizer, amino acids to be peptides. Within that set, those Takeda, and Amgen. Those companies have made containing 10 or more are classed as polypeptides.
    [Show full text]
  • Linaclotide: a Novel Therapy for Chronic Constipation and Constipation- Predominant Irritable Bowel Syndrome Brian E
    Linaclotide: A Novel Therapy for Chronic Constipation and Constipation- Predominant Irritable Bowel Syndrome Brian E. Lacy, PhD, MD, John M. Levenick, MD, and Michael D. Crowell, PhD, FACG Dr. Lacy is Section Chief of Gastroenter- Abstract: Chronic constipation and irritable bowel syndrome ology and Hepatology and Dr. Levenick (IBS) are functional gastrointestinal disorders that significantly is a Gastroenterology Fellow in the affect patients’ quality of life. Chronic constipation and IBS are Division of Gastroenterology and prevalent—12% of the US population meet the diagnostic crite- Hepatology at Dartmouth-Hitchcock Medical Center in Lebanon, New ria for IBS, and 15% meet the criteria for chronic constipation— Hampshire. Dr. Crowell is a Professor and these conditions negatively impact the healthcare system of Medicine in the Division of from an economic perspective. Despite attempts at dietary Gastroenterology and Hepatology at modification, exercise, or use of over-the-counter medications, Mayo Clinic in Scottsdale, Arizona. many patients have persistent symptoms. Alternative treatment options are limited. This article describes linaclotide (Linzess, Address correspondence to: Dr. Brian E. Lacy Ironwood Pharmaceuticals/Forest Pharmaceuticals), a new, first- Division of Gastroenterology and in-class medication for the treatment of chronic constipation Hepatology, Area 4C and constipation-predominant IBS. Dartmouth-Hitchcock Medical Center 1 Medical Center Drive Lebanon, NH 03756; Tel: 603-650-5215; Fax: 603-650-5225; onstipation is
    [Show full text]
  • Ferring Pharmaceuticals Inc. Page 1 of 13 HIGHLIGHTS OF
    HIGHLIGHTS OF PRESCRIBING INFORMATION ---------------------DOSAGE FORMS AND STRENGTHS---------------------- CLENPIQ oral solution: Each bottle contains 10 mg of sodium picosulfate, These highlights do not include all the information needed to use ® 3.5 g of magnesium oxide, and 12 g of anhydrous citric acid in 160 mL of CLENPIQ safely and effectively. See full prescribing information for solution (3) CLENPIQ. -------------------------------CONTRAINDICATIONS------------------------------ ® • Patients with severe reduced renal impairment (creatinine clearance less CLENPIQ (sodium picosulfate, magnesium oxide, and anhydrous citric than 30 mL/minute) (4, 5.3, 8.6) acid) oral solution • Gastrointestinal (GI) obstruction or ileus (4) Initial U.S. Approval: 2012 • Bowel perforation (4) • ----------------------------RECENT MAJOR CHANGES-------------------------- Toxic colitis or toxic megacolon (4) Indications and Usage (1) 08/2019 • Gastric retention (4) Dosage and Administration (2.1) 10/2019 • Hypersensitivity to any of the ingredients in CLENPIQ (4) Dosage and Administration (2.2) 08/2019, 10/2019 Dosage and Administration, Day-Before Dosage Regimen (2.3) -----------------------WARNINGS AND PRECAUTIONS------------------------ Removed 10/2019 • Risk of fluid and electrolyte abnormalities, arrhythmia, seizures, and renal Warnings and Precautions (5.1) 08/2019 impairment: Encourage adequate hydration, assess concurrent medications, and consider laboratory assessments prior to and after use. (5.1, 5.2, 5.3, 5.4, ----------------------------INDICATIONS AND USAGE--------------------------- 7.1) CLENPIQ® is a combination of sodium picosulfate, a stimulant laxative, and • Use in patients with renal impairment or taking concomitant medications magnesium oxide and anhydrous citric acid, which form magnesium citrate, that affect renal function: Use caution, ensure adequate hydration, and an osmotic laxative, indicated for cleansing of the colon as a preparation for consider testing.
    [Show full text]
  • Laxatives for the Management of Constipation in People Receiving Palliative Care (Review)
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by UCL Discovery Laxatives for the management of constipation in people receiving palliative care (Review) Candy B, Jones L, Larkin PJ, Vickerstaff V, Tookman A, Stone P This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2015, Issue 5 http://www.thecochranelibrary.com Laxatives for the management of constipation in people receiving palliative care (Review) Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 PLAINLANGUAGESUMMARY . 2 BACKGROUND .................................... 2 OBJECTIVES ..................................... 4 METHODS ...................................... 4 RESULTS....................................... 7 Figure1. ..................................... 8 Figure2. ..................................... 9 Figure3. ..................................... 10 DISCUSSION ..................................... 13 AUTHORS’CONCLUSIONS . 14 ACKNOWLEDGEMENTS . 14 REFERENCES ..................................... 15 CHARACTERISTICSOFSTUDIES . 17 DATAANDANALYSES. 26 ADDITIONALTABLES. 26 APPENDICES ..................................... 28 WHAT’SNEW..................................... 35 HISTORY....................................... 35 CONTRIBUTIONSOFAUTHORS . 36 DECLARATIONSOFINTEREST . 36 SOURCESOFSUPPORT . 36 DIFFERENCES
    [Show full text]
  • Assessment Report on Ricinus Communis L., Oleum Final
    2 February 2016 EMA/HMPC/572973/2014 Committee on Herbal Medicinal Products (HMPC) Assessment report on Ricinus communis L., oleum Final Based on Article 10a of Directive 2001/83/EC as amended (well-established use) Herbal substance(s) (binomial scientific name Ricinus communis L., oleum (castor oil) of the plant, including plant part) Herbal preparation Fatty oil obtained from seeds of Ricinus communis L. by cold expression Pharmaceutical forms Herbal preparation in liquid or solid dosage forms for oral use Rapporteur C. Purdel Peer-reviewer B. Kroes 30 Churchill Place ● Canary Wharf ● London E14 5EU ● United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website www.ema.europa.eu/contact An agency of the European Union © European Medicines Agency, 2016. Reproduction is authorised provided the source is acknowledged. Table of contents Table of contents ................................................................................................................... 2 1. Introduction ....................................................................................................................... 4 1.1. Description of the herbal substance(s), herbal preparation(s) or combinations thereof .. 4 1.2. Search and assessment methodology ..................................................................... 6 2. Data on medicinal use ........................................................................................................ 6 2.1. Information about products on the market .............................................................
    [Show full text]
  • Chronic Constipation: an Evidence-Based Review
    J Am Board Fam Med: first published as 10.3122/jabfm.2011.04.100272 on 7 July 2011. Downloaded from CLINICAL REVIEW Chronic Constipation: An Evidence-Based Review Lawrence Leung, MBBChir, FRACGP, FRCGP, Taylor Riutta, MD, Jyoti Kotecha, MPA, MRSC, and Walter Rosser MD, MRCGP, FCFP Background: Chronic constipation is a common condition seen in family practice among the elderly and women. There is no consensus regarding its exact definition, and it may be interpreted differently by physicians and patients. Physicians prescribe various treatments, and patients often adopt different over-the-counter remedies. Chronic constipation is either caused by slow colonic transit or pelvic floor dysfunction, and treatment differs accordingly. Methods: To update our knowledge of chronic constipation and its etiology and best-evidence treat- ment, information was synthesized from articles published in PubMed, EMBASE, and Cochrane Database of Systematic Reviews. Levels of evidence and recommendations were made according to the Strength of Recommendation taxonomy. Results: The standard advice of increasing dietary fibers, fluids, and exercise for relieving chronic constipation will only benefit patients with true deficiency. Biofeedback works best for constipation caused by pelvic floor dysfunction. Pharmacological agents increase bulk or water content in the bowel lumen or aim to stimulate bowel movements. Novel classes of compounds have emerged for treating chronic constipation, with promising clinical trial data. Finally, the link between senna abuse and colon cancer remains unsupported. Conclusions: Chronic constipation should be managed according to its etiology and guided by the best evidence-based treatment.(J Am Board Fam Med 2011;24:436–451.) copyright. Keywords: Chronic Constipation, Clinical Review, Evidence-Based Medicine, Family Medicine, Gastrointestinal Problems, Systematic Review The word “constipation” has varied meanings for was established in 1991 by Drossman et al, primar- different individuals.
    [Show full text]
  • Tegaserod in the Treatment of Constipation-Predominant Functional Gastrointestinal Disorders
    DRUG PROFILE Tegaserod in the treatment of constipation-predominant functional gastrointestinal disorders Anurag Agrawal & Irritable bowel syndrome is a common condition for which, until recently, treatment Peter Whorwell† options have been limited. Tegaserod has selective serotonin subtype 4 receptor agonist †Author for correspondence activity and acts by increasing gastrointestinal motility, secretion and possibly reducing ERC Building, First Floor, Wythenshawe Hospital, visceral sensitivity. It has been developed to treat patients with irritable bowel syndrome Southmoor Road, who suffer from abdominal pain, constipation and bloating. Studies so far suggest that it is Manchester, M23 9LT, an effective treatment for these symptoms with an excellent safety profile. Its role in other UK Tel.: +44 161 291 5813 functional gastrointestinal disorders, such as functional dyspepsia, is still being assessed. Fax: +44 161 291 4184 This review describes the structure, pharmacokinetic and pharmacodynamic properties of tegaserod and its effect on gastrointestinal physiology, as well as its clinical utility. Irritable bowel syndrome (IBS) is the most com- drugs such as antidiarrheals, laxatives, antispas- mon condition dealt with by gastroenterolo- modics and antidepressants. Behavioral therapy gists, accounting for up to 30% of their practice is sometimes tried in patients who do not and 10% of primary care case loads [1]. It is respond to conventional treatment. characterized by abdominal pain or discomfort In addition to its costs to the patient, IBS also often related to a change in bowel habit and fre- has a significant direct and indirect economic quently exacerbated by eating. Investigation burden. The direct cost in terms of healthcare reveals no structural abnormality, although a utilization has been estimated to be between variety of gastrointestinal (GI) physiological US$1.7–10 billion/year in the USA alone.
    [Show full text]
  • Constipation
    Constipation Constipation is defined as having a bowel movement fewer than three times per week. With constipation stools are usually hard, dry, Esophagus small in size, and difficult to eliminate. Some people who are constipated find it painful to Liver Stomach have a bowel movement and often experience straining, bloating, and the sensation of a full Pancreas bowel. Large Some people think they are constipated if they intestine do not have a bowel movement every day. However, normal stool elimination may be Small three times a day or three times a week, intestine depending on the person. Rectum Constipation is a symptom, not a disease. Anus Almost everyone experiences constipation at some point in their life, and a poor diet Appendix typically is the cause. Most constipation is temporary and not serious. Understanding its The digestive tract. causes, prevention, and treatment will help most people find relief. Self-treatment of constipation with overthe- counter (OTC) laxatives is by far the most Who gets constipated? common aid. Around $725 million is spent on Constipation is one of the most common laxative products each year in America. gastrointestinal complaints in the United States. More than 4 million Americans have frequent What causes constipation? constipation, accounting for 2.5 million To understand constipation, it helps to know physician visits a year. Those reporting how the colon, or large intestine, works. As food constipation most often are women and adults moves through the colon, the colon absorbs ages 65 and older. Pregnant women may have water from the food while it forms waste constipation, and it is a common problem products, or stool.
    [Show full text]
  • Relative Efficacy of Tegaserod in a Systematic Review and Network Meta-Analysis of Licensed Therapies for Irritable Bowel Syndrome with Constipation
    This is a repository copy of Relative Efficacy of Tegaserod in a Systematic Review and Network Meta-analysis of Licensed Therapies for Irritable Bowel Syndrome with Constipation.. White Rose Research Online URL for this paper: http://eprints.whiterose.ac.uk/149160/ Version: Accepted Version Article: Black, CJ, Burr, NE orcid.org/0000-0003-1988-2982 and Ford, AC orcid.org/0000-0001-6371-4359 (2020) Relative Efficacy of Tegaserod in a Systematic Review and Network Meta-analysis of Licensed Therapies for Irritable Bowel Syndrome with Constipation. Clinical Gastroenterology and Hepatology, 18 (5). 1238-1239.E1. ISSN 1542-3565 https://doi.org/10.1016/j.cgh.2019.07.007 © 2019 by the AGA Institute. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/). Reuse This article is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs (CC BY-NC-ND) licence. This licence only allows you to download this work and share it with others as long as you credit the authors, but you can’t change the article in any way or use it commercially. More information and the full terms of the licence here: https://creativecommons.org/licenses/ Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing [email protected] including the URL of the record and the reason for the withdrawal request. [email protected] https://eprints.whiterose.ac.uk/ Black et al. Page 1 of 9 Accepted for publication 3rd July 2019 TITLE PAGE Title: Relative Efficacy of Tegaserod in a Systematic Review and Network Meta- analysis of Licensed Therapies for Irritable Bowel Syndrome with Constipation.
    [Show full text]