FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2897071318> ?p ?o ?g. }

• W2897071318 endingPage "253.e5" @default.
• W2897071318 startingPage "229" @default.
• W2897071318 abstract "Opioid medications are some of the most commonly prescribed medications for acute and chronic pain in the United States. In 2016, nearly 92 million US adults, or approximately 38% of the population, were prescribed opioids, according to results from the National Survey on Drug Use and Health.1Han B. Compton W.M. Blanco C. et al.Prescription opioid use, misuse, and use disorders in u.s. adults: 2015 national survey on drug use and health.Ann Intern Med. 2017; 167: 293-301Crossref PubMed Scopus (582) Google Scholar As a result of the widespread use of opioids, the prevalence of opioid-related adverse effects has increased markedly. Gastrointestinal (GI) side effects, such as nausea, vomiting, gastroesophageal reflux, gastroparesis, anorexia, bloating, abdominal spasms, and constipation, are common and collectively referred to as opioid-induced bowel dysfunction. Of these adverse effects, opioid-induced constipation (OIC) is the most problematic manifestation of opioid-induced bowel dysfunction, as patients rarely develop a tolerance to OIC.2Nelson A.D. Camilleri M. Opioid-induced constipation: advances and clinical guidance.Ther Adv Chronic Dis. 2016; 7: 121-134Crossref PubMed Scopus (77) Google Scholar Up to one-third of patients may miss or decrease their analgesic medications due to GI side effects, leading to untreated chronic pain and a reduction in health-related quality of life (QOL).3Hjalte F. Ragnarson Tennvall G. Welin K.O. et al.Treatment of severe pain and opioid-induced constipation: an observational study of quality of life, resource use, and costs in Sweden.Pain Ther. 2016; 5: 227-236Crossref PubMed Scopus (5) Google Scholar, 4Nelson A.D. Camilleri M. Chronic opioid induced constipation in patients with nonmalignant pain: challenges and opportunities.Therap Adv Gastroenterol. 2015; 8: 206-220Crossref PubMed Scopus (59) Google Scholar The true prevalence of OIC is unknown, given the failure to recognize OIC as an adverse effect of chronic opioid use and variability in criteria used to diagnose OIC. Reported prevalence rates in the published literature range markedly, from 22% to 81%, depending on the population studied.5Abramowitz L. Beziaud N. Labreze L. et al.Prevalence and impact of constipation and bowel dysfunction induced by strong opioids: a cross-sectional survey of 520 patients with cancer pain: DYONISOS study.J Med Econ. 2013; 16: 1423-1433Crossref PubMed Scopus (66) Google Scholar, 6Cowan D.T. Wilson-Barnett J. Griffiths P. et al.A survey of chronic noncancer pain patients prescribed opioid analgesics.Pain Med. 2003; 4: 340-351Crossref PubMed Scopus (86) Google Scholar, 7Ducrotte P. Milce J. Soufflet C. et al.Prevalence and clinical features of opioid-induced constipation in the general population: A French study of 15,000 individuals.United European Gastroenterol J. 2017; 5: 588-600Crossref PubMed Scopus (20) Google Scholar Health care utilization and health care costs are higher in patients with OIC. In a retrospective analysis of Medicaid patients with non-cancer pain and OIC, the annual median incremental cost increase over similar patients without constipation was $4000.8Olufade T. Kong A.M. Princic N. et al.Comparing healthcare utilization and costs among Medicaid-insured patients with chronic noncancer pain with and without opioid-induced constipation: a retrospective analysis.Am Health Drug Benefits. 2017; 10: 79-86PubMed Google Scholar Similar findings have been observed in Medicare patients, privately insured patients, and patients with cancer-related pain.9Candrilli S.D. Davis K.L. Iyer S. Impact of constipation on opioid use patterns, health care resource utilization, and costs in cancer patients on opioid therapy.J Pain Palliat Care Pharmacother. 2009; 23: 231-241Crossref PubMed Scopus (54) Google Scholar, 10Fernandes A.W. Kern D.M. Datto C. et al.Increased burden of healthcare utilization and cost associated with opioid-related constipation among patients with noncancer Pain.Am Health Drug Benefits. 2016; 9: 160-170PubMed Google Scholar, 11Kwong W.J. Diels J. Kavanagh S. Costs of gastrointestinal events after outpatient opioid treatment for non-cancer pain.Ann Pharmacother. 2010; 44: 630-640Crossref PubMed Scopus (47) Google Scholar, 12Wan Y. Corman S. Gao X. et al.Economic burden of opioid-induced constipation among long-term opioid users with noncancer pain.Am Health Drug Benefits. 2015; 8: 93-102PubMed Google Scholar Mechanistically, OIC is mediated by activation of peripheral μ-, δ-, and κ-opioid receptors in the enteric nervous system within the GI tract. Opioid agonists bind (primarily) to the μ-opioid receptor and lead to a decrease in peristaltic activity and a reduction of mucosal secretions throughout the GI tract, resulting in delayed gastric emptying, slowed intestinal transit, and increased intestinal fluid absorption. In addition, opioids can cause disordered anal sphincter function.13Kumar L. Barker C. Emmanuel A. Opioid-induced constipation: pathophysiology, clinical consequences, and management.Gastroenterol Res Pract. 2014; 2014: 141737Crossref PubMed Scopus (105) Google Scholar Until 2015, consistent criteria were not systematically used in clinical trials to make the diagnosis of OIC.14Gaertner J. Siemens W. Camilleri M. et al.Definitions and outcome measures of clinical trials regarding opioid-induced constipation: a systematic review.J Clin Gastroenterol. 2015; 49: 9-16Crossref PubMed Scopus (64) Google Scholar A multidisciplinary working group proposed a consensus definition of OIC to help inform clinical trials and defined OIC as “a change from baseline bowel habits when initiating opioid therapy that is characterized by any of the following: reduced bowel movement (BM) frequency, development or worsening of straining to pass BMs, a sense of incomplete rectal evacuation or harder stool frequency.”14Gaertner J. Siemens W. Camilleri M. et al.Definitions and outcome measures of clinical trials regarding opioid-induced constipation: a systematic review.J Clin Gastroenterol. 2015; 49: 9-16Crossref PubMed Scopus (64) Google Scholar The Rome IV criteria recently defined OIC as new or worsening symptoms of constipation when initiating, changing, or increasing opioid therapy that must include 2 or more of the following >25% of the time: straining, lumpy/hard stools, sensation of incomplete evacuation, sensation of anorectal obstruction/blockage, manual maneuvers to facilitate defecations, or <3 SPMs per week, with loose stools rarely present without the use of laxatives.15Drossman D.A. Functional gastrointestinal disorders: what's new for Rome IV?.Lancet Gastroenterol Hepatol. 2016; 1: 6-8Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 16Drossman D.A. Hasler W.L. Rome IV-Functional GI disorders: disorders of gut-brain interaction.Gastroenterology. 2016; 150: 1257-1261Abstract Full Text Full Text PDF PubMed Scopus (698) Google Scholar Treatment of OIC requires a multifaceted approach, which includes non-pharmacologic (dietary and lifestyle modifications) and pharmacologic approaches to reduce OIC symptoms, while ensuring adequate analgesia. Several new pharmacologic therapies have been developed in recent years, many of which have unique mechanisms of action targeted specifically to the treatment of OIC. In this review, we focus on the pharmacologic management of OIC using laxatives, selective 5-HT serotonin receptor agonists, chloride channel activators, and peripherally acting μ-opioid receptor antagonists (PAMORAs). This technical review accompanies and informs the American Gastroenterological Association (AGA) guideline on the pharmacologic management of OIC and provides evidence-based information to guide patients, clinicians, and policy makers in the management of adults with OIC. The target audience for this technical review (and accompanying guideline) is gastroenterologists consulted specifically for the management of OIC. As a result, this review does not address strategies such as opioid switching, opioid rotation, opioid dose reduction, or the use of novel fixed-ratio opioid-containing combination medications, as these are outside the scope of practice of most gastroenterologists. Furthermore, this guideline does not systematically address the prevention of OIC. The technical review panel included gastroenterologists with clinical and research expertise, a methodologist with experience in evidence appraisal and guideline development, and 2 trainee methodologists. Financial and non-financial conflicts of interest of all participants were managed according to AGA policies and no member of this technical review panel had any conflicts of interest. The panel held periodic telephone conferences and one face-to-face meeting to conduct this work. Methods for deriving focused clinical questions, systematically reviewing and rating the quality of evidence for each outcome, and rating the overall quality of evidence were based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework, which has been described in more detail previously.17Sultan S. Falck-Ytter Y. Inadomi J.M. The AGA institute process for developing clinical practice guidelines part one: grading the evidence.Clin Gastroenterol Hepatol. 2013; 11: 329-332Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar In light of the recent development of several new agents for the management of OIC, the AGA clinical guideline committee proposed this topic as a rapid review with the goal of reducing the time from topic proposal to guideline publication and expediting the process. While the panel generally followed the steps outlined by the AGA clinical guideline committee, the following “shortcuts” were taken: (1) initial review of titles and abstracts was done by 1 of 3 authors (BH, SS, SS) and only the excluded titles and abstracts were reviewed by a second author. This reduced the title and abstract review process time, but did not reduce the sensitivity for full-text review; (2) data extraction for each study was performed by only 1 of 3 authors (BH, SS, SS); and (3) risk of bias assessment was initially determined by a single author (BH or SS) and when concerns arose, a second author was consulted (SS). Using the PICO format, which frames a clinical question by defining a specific patient population (P), intervention (I), comparator (C), and outcomes (O), the panel prioritized the questions to be addressed by this guideline (see Table 1). The final set of questions and statements was approved by the AGA Governing Board.Table 1PICO QuestionsPopulation(s)Intervention(s)ComparatorOutcome(s) a prioriStudiesAdults with OIC (ambulatory, adult outpatients on chronic opioids with constipation defined by clinical symptoms [<3 SBMs], physician diagnosis, or other study-specific diagnostic criteria)Osmotic or stimulant laxativesOsmotic: PEGPAMORAs: naloxegol, alvimopan, naldemedine, methylnaltrexoneSecretagogues: lubiprostoneSelective 5HT4 agonist: prucalopridePlacebo or usual care or active comparatorSPMs, number per weekLack of straining during defecationBM within prespecified time frame, time to laxationRFBMsReduction/cessation of laxativesReduction in painful defecationStool frequencyStool consistency (BSFS)PAC-QOLPROMAEs leading to treatment discontinuation (ie, allergic reactions, death, cardiac events, abdominal pain, diarrhea, incontinence, nocturnal BMs)Reversal of analgesia or exacerbation of chronic painCost-effectivenessRCTObservational studies (for the harm outcome)Systematic review/meta-analysis Open table in a new tab Members of the technical review and guideline committee selected patient-important outcomes for each question a priori. The panel rated the relative importance of each outcome for decision making on a scale of 1–10. Outcomes receiving a score of 7–10 were considered critical (for decision making), 4–6 as important (for decision making), and 1–3 less important (for decision making). This initial list of outcomes was then further refined during the evidence review by the technical review panel. Ultimately, the following outcomes were considered critical or important for decision making and therefore included in the evidence profiles: spontaneous bowel movement (SBM) response using the responder definition—defined as ≥3 SBMs/wk and ≥1 SBM/wk over baseline for a predefined number of weeks (critical); increase in stool frequency (important); improvement in stool consistency (Bristol Stool Form Scale) (important); reduction in painful defecation/lack of straining (important); QOL (important); and adverse events (AEs) leading to treatment discontinuation (important). One additional outcome was included for methylnaltrexone: laxation response (important), which was defined as a spontaneous or rescue-free bowel movement within 4 hours of first dose of intervention. Over the last few decades, clinical trials for constipation and OIC have changed their efficacy end points. Earlier trials included end points such as increase in BM frequency (measured as change from baseline to the end of the treatment period) or time to laxation (measured in hours). Newer trials placed more emphasis on SBMs, denoting BMs without intake of any “rescue” medication (such as a laxatives) 24 hours before the BM and combined end points that capture longer-term sustained improvements in SBMs over a defined time period. This is consistent with outcomes used in studies of pharmacologic therapies for chronic idiopathic constipation. Based on guidance from the Food and Drug Administration (FDA) and European Medicines Agency, contemporary OIC clinical trials primarily use a “responder analysis” as their primary end point, where response is defined as ≥3 SBMs and ≥1 SBM/wk over baseline for a specified duration or number of weeks (eg, at least 75% of the total duration of the study or for 9 of 12 weeks). A BM was classified as spontaneous if no laxative had been used in the prior 24 hours. This responder outcome defines a minimum SBMs per week for response (minimum threshold of at least 1 additional SBM over baseline), excludes BMs achieved with rescue laxatives, and specifies that the improvement must be sustained to establish clinically meaningful improvement. If the FDA responder outcome was not available, an effort was made to determine whether the reported study outcome was similar enough to the responder definition to inform the pooled effect estimate. For example, rescue-free bowel movement (RFBM), defined as ≥3 RFBMs/wk for the duration of the study (without an accompanying increase in weekly RFBMs) or ≥3 RFBMs/wk and an increase of ≥1 RFBM/wk from baseline for at least 3 of the first 4 weeks, was used for some studies of methylnalteroxe. Additional patient-important outcomes included improvement in stool consistency, reduction in straining, or lack of painful defecation. Stool consistency was assessed using the Bristol Stool Form Scale (BSFS) and reduction/lack of straining or painful defecation were assessed on a 5-point scale ranging from 1 (no straining) to 5 (extreme amount of straining); mean differences (MDs) in change from baseline for the intervention and placebo arms were reported. The majority of trials did not provide specific cutoffs or define a minimal clinically important difference in outcomes for these scales. Furthermore, no responder definition was used to analyze differences between groups. QOL was frequently assessed using the Patient Assessment of Constipation-Quality of Life (PAC-QOL) questionnaire, which comprises 28 questions and 4 subscales, including physical discomfort, psychosocial discomfort, worries and concerns, and satisfaction. Each element is scored on a scale of 0–4 (least to the greatest effect), and higher scores indicate reduced QOL. A 1-point improvement in PAC-QOL scores has been validated as a relevant definition of response for treatment group comparisons.18Dubois D. Gilet H. Viala-Danten M. et al.Psychometric performance and clinical meaningfulness of the Patient Assessment of Constipation-Quality of Life questionnaire in prucalopride (RESOLOR) trials for chronic constipation.Neurogastroenterol Motil. 2010; 22: e54-e63Crossref PubMed Scopus (60) Google Scholar, 19Marquis P. De La Loge C. Dubois D. et al.Development and validation of the Patient Assessment of Constipation Quality of Life questionnaire.Scand J Gastroenterol. 2005; 40: 540-551Crossref PubMed Scopus (363) Google Scholar While our initial list of relevant outcomes included patient-reported outcome measures (PROMs), such as the Patient Assessment of Constipation-Symptoms, Bowel Function Index (BFI), and Bowel Function Diary, few published clinical trials utilized these outcomes consistently, limiting the ability to pool effects for these PROMs across studies. The BFI has recently been endorsed as a tool to identify patients likely to benefit from OIC treatment.20Argoff C.E. Brennan M.J. Camilleri M. et al.Consensus recommendations on initiating prescription therapies for opioid-induced constipation.Pain Medicine (United States). 2015; 16: 2324-2337Crossref PubMed Scopus (80) Google Scholar This PROM draws from previously developed severity measures (Rome Criteria and Patient Assessment of Constipation-Symptoms).21Rentz A.M. Yu R. Muller-Lissner S. et al.Validation of the Bowel Function Index to detect clinically meaningful changes in opioid-induced constipation.J Med Econ. 2009; 12: 371-383Crossref PubMed Scopus (149) Google Scholar Developed to evaluate the effects of oxycodone prolonged release (PR)/naloxone PR, an opioid agonist/antagonist combination for chronic pain, BFI has been used in 7 randomized controlled trials (RCTs). BFI has also been validated in one small non-intervention trial.22Rentz A.M. van Hanswijck de Jonge P. Leyendecker P. et al.Observational, nonintervention, multicenter study for validation of the Bowel Function Index for constipation in European countries.Curr Med Res Opin. 2011; 27: 35-44Crossref PubMed Scopus (47) Google Scholar BFI measures a sense of incomplete evacuation, ease of defecation, and personal judgment of the patient regarding constipation over the previous 7 days. Using a numeric analogue scale, a score of 0–100 is assigned by the patient to each of the 3 components. Higher scores indicate more severe symptoms. These 3 scores are then averaged to achieve the final BFI score. Scores ≤28.8 have been demonstrated to include 95% of all non-constipated patients. A change in BFI ≥12 has been proposed as a clinically meaningful change.23Ueberall M.A. Muller-Lissner S. Buschmann-Kramm C. et al.The Bowel Function Index for evaluating constipation in pain patients: definition of a reference range for a non-constipated population of pain patients.J Int Med Res. 2011; 39: 41-50Crossref PubMed Scopus (86) Google Scholar Recent consensus recommendations (2014) recommend the BFI as a simple, relevant, and easy-to-administer tool to identify individuals who may benefit from OIC therapy.20Argoff C.E. Brennan M.J. Camilleri M. et al.Consensus recommendations on initiating prescription therapies for opioid-induced constipation.Pain Medicine (United States). 2015; 16: 2324-2337Crossref PubMed Scopus (80) Google Scholar A score of ≥30 was selected by this panel based on the fact that 95% on non-constipated patients would fall in the range below this number. BFI may identify patients with OIC and provide an easy-to-use measure for patient selection and monitoring for response, but it must be noted it was not developed for this purpose, and it was validated from an enriched population of patients enrolled in clinical trials for the treatment of OIC. For SBM response, the threshold for a clinically meaningful benefit, based on consensus among panel members, was set at a number needed to treat of approximately 10, that is, 10 more responders for every 100 treated patients compared to placebo. The threshold for clinically meaningful harm was set at a number needed to harm of approximately 5—5 more AEs leading to treatment discontinuation for every 100 treated patients compared to placebo. For outcomes such as improvement in stool consistency or reduction in straining/painful defecation, a non-contextualized approach relying on statistical significance was used to inform judgments about the quality or certainty of the evidence.24Hultcrantz M. Rind D. Akl E.A. et al.The GRADE Working Group clarifies the construct of certainty of evidence.J Clin Epidemiol. 2017; 87: 4-13Abstract Full Text Full Text PDF PubMed Scopus (293) Google Scholar A search of the medical literature was conducted by an information specialist using the following databases: MEDLINE (1950 to February 2017), EMBASE and EMBASE Classic (1947 to February 2017), and the Cochrane Central Register of Controlled Trials, and health technology assessments to identify RCTs using a combination of controlled vocabulary and text words. This search was updated to look for additional studies that were published from February 2017 to May 2018 (just after the public comment was terminated). Trials examining the effect of pharmacologic therapies (laxatives, methylnaltrexone, naloxegol, alvimopan, naldemedine, prucalopride, and lubiprostone) in adult patients with OIC (with and without cancer) were eligible for inclusion. Studies were restricted to English language and letters, notes, case reports, and comments were excluded. Abstracts of the papers identified by the initial search were evaluated independently by 1 of 3 investigators for appropriateness. Hand searching was not performed. Full-text version of all potentially relevant studies were obtained and evaluated in detail. Bibliographies of all identified relevant studies were used to perform a recursive search. Articles were assessed independently by 1 of 3 investigators using predefined eligibility criteria. Trials using any dose of pharmacologic therapy were considered eligible. Studies that recruited patients with organic or chronic idiopathic constipation were ineligible. A diagnosis of OIC was based on a history of constipation associated with the onset of opioid analgesic use or constipation as defined by the Rome IV criteria (<3 SBMs/wk and 1 additional constipation-related symptom ≥25% of the time in the presence of opioid therapy). The specific definitions of OIC used as part of study inclusion criteria in individual studies is included Table 2. Only trials with at least a 4-week duration of treatment were considered, with the exception of methylnaltrexone (2-week minimum), as earlier clinical trials of methylnaltrexone were generally shorter in duration. Studies evaluating efficacy of pharmacologic therapies in postoperative settings were excluded. First or senior authors of studies were contacted to provide additional information on trials where required.Table 2Characteristics of Included Studies and Definitions of Opioid-Induced Constipation and OutcomesStudySettingPatient groupOIC definitionInterventionEvidence profile outcome definitionsSBM responseChange in SBM frequencyReduction in strainingStool consistency improvementQOLAEsLaxativesPEGFreedman, 199726Freedman M.D. Schwartz H.J. Roby R. et al.Tolerance and efficacy of polyethylene glycol 3350/electrolyte solution versus lactulose in relieving opiate induced constipation: a double-blinded placebo-controlled trial.J Clin Pharmacol. 1997; 37: 904-907Crossref PubMed Scopus (95) Google ScholarSingle-center in a US outpatient methadone programChronic non-malignant pain, not laxative refractory (n = 57)Enrollment into the drug-dependency program with a complaint of constipation in patients who previously sought laxative useLactulose 30 mL nightly, or PEG-3350 (dose not reported) nightly for 7 wk———Weekly stool mean of patient reported hard, soft, or loose stools——PAMORAsNaloxegolChey, 201435Chey W.D. Webster L. Sostek M. et al.Naloxegol for opioid-induced constipation in patients with noncancer pain.New England Journal of Medicine. 2014; 370: 2387-2396Crossref PubMed Scopus (259) Google ScholarKODIAC-04KODIAC-05Europe and US, 115 secondary and tertiary care centersEurope and US, 142 secondary and tertiary centersChronic non-malignant pain, at least 50% with inadequate laxative response (n = 641)Chronic non-malignant pain, at least 50% with inadequate laxative response (n = 696)Stable opioid use (total daily dose of 30–1000mg of morphine, or equivalent, for ≥4 wk) AND <3 SBMs/wk associated with ≥1 of the following: hard/lumpy stools, straining, sensation of obstruction, or incomplete evacuation in ≥25% of BMsNaloxegol 12.5 mg or 25 mg oral daily for 12 wk≥3 SBMs/wk and an increase from baseline of ≥1 SBM for ≥9 of 12 wk and for ≥3 of the final 4 wkMean change in SBMs/wk from baseline5-point scale, ranging from 1 (no straining) to 5 (extreme amount of straining), compared to baselineBSFS at the end of treatment, compared to baseline—AE leading to treatment discontinuationWebster, 201336Webster L. Dhar S. Eldon M. et al.A phase 2, double-blind, randomized, placebo-controlled, dose-escalation study to evaluate the efficacy, safety, and tolerability of naloxegol in patients with opioid-induced constipation.Pain. 2013; 154: 1542-1550Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar54 sites in 4 countries (Germany, US, Romania, Canada), setting not reportedChronic non-malignant pain, not laxative refractory (n = 207)Opioid use (total daily dose of 30–1000 mg of morphine, or equivalent, for ≥2 wk) AND <3 SBMs/wk associated with ≥1 of the following: hard/lumpy stools, straining, sensation of obstruction, or incomplete evacuation in ≥25% of BMsNaloxegol 5 mg, 25 mg, or 50 mg oral daily for 4 wk————PAC-QOLAE leading to treatment discontinuationWebster, 201438Webster L. Chey W.D. Tack J. et al.Randomised clinical trial: the long-term safety and tolerability of naloxegol in patients with pain and opioid-induced constipation.Alimentary pharmacology & therapeutics. 2014; 40: 771-779Crossref PubMed Scopus (102) Google ScholarMulticenterChronic non-malignant pain, not laxative refractory (n = 534)Stable opioid use (total daily dose of 30–1000 mg of morphine, or equivalent) AND <3 SBMs/wk on average with ≥1 of the following symptoms in ≥25% of BMs: BSFS type 1 or 2; moderate, severe or very severe straining; or incomplete BM.Naloxegol 25 mg oral daily—————AE leading to treatment discontinuationAlvimopanIrving, 201140Irving G. Penzes J. Ramjattan B. et al.A randomized, placebo-controlled phase 3 trial (study sb-767905/013) of alvimopan for opioid-induced bowel dysfunction in patients with non-cancer pain.Journal of Pain. 2011; 12: 175-184Abstract Full Text Full Text PDF PubMed Scopus (55) Google ScholarMulti-national, 153 secondary and tertiary care centersChronic non-malignant pain, laxative status not reported (n = 485)Stable opioid use (≥1 full opioid agonist at a stable dose of at least 30 mg/d oral morphine equivalents except for codeine at least ∼20 mg morphine equivalents for ≥1 month) AND <3 SBMs/wk and ≥1 of the following: sense of incomplete evacuation after passing stool, straining, lumpy hard stools or small pellets in ≥25% of BMsAlvimopan 0.5 mg daily or 0.5 mg bid for 12 wk≥3 SBMs/wk over the treatment period and average increase of ≥1 SBM/wk from baselineMean change in SBMs/wk from to baseline4-point scale (no, mild, moderate, or severe straining) with a responder having a mean straining score ≤2 over the treatment period4-point scale (1 = watery/loose, 2 = semi-solid/soft, 3 = lumpy hard, 4 = small pellets) with a responder having an average score of between 1.72 and 2.25—AE leading to treatment discontinuationJansen, 201141Jansen J.P. Lorch D. Langan J. et al.A randomized, placebo-controlled phase 3 trial (Study SB-767905/012) of alvimopan for opioid-induced bowel dysfunction in patients with non-cancer pain.J Pain. 2011; 12: 185-193Abstract Full Text Full Text PDF PubMed Scopus (57) Google ScholarMulti-national (North America and Europe), 148 secondary and tertiary care centersChronic non-malignant pain, laxative status not reported (n = 518)Stable opioid use (≥1 full opioid agonist at a stable dose of at least 30 mg/d oral morphine equivalents except for codeine at least ∼20 mg morphine equivalents for ≥1 month) AND <3 SBMs/wk and ≥1 of the following: sense of incomplete evacuation after passing stool, straining, lumpy hard stools or small pellets in ≥25% of BMsAlvimopan daily or 0.5 mg bid for 12 wk≥3 SBMs/wk during therapy with an increase of ≥1 SBM/wk from baselineMean change in SBMs/wk from baseline4-point scale (no, mild, moderate, or severe straining) with a responder having a mean straining score ≤2 over the treatment period4-point scale (1 = watery/loose, 2 = semisolid/soft, 3 = lumpy hard, 4 = small pellets) with a responder having an average score of between 1.72 and 2.25—AE leading to treatment discontinuation; cardiovascular eventsWebster, 200842Webster L. Jansen J.P. Peppin J. et al.Alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist for the treatment of opioid-induced bowel dysfunction: results from a randomized, double-blind, placebo-controlled, dose-finding study in subjects taking opioids for chronic non-cancer pain.Pain. 2008; 137: 428-440Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar9 countries, 113 secondary and tertiary care centersChronic non-malignant pain, not laxative refractory (n = 522)Stable opioid use (a full opioid agonist other than meperidine and propoxyphene at a dose of ≥30 mg/d oral morphine equivalents) AND <3 SBMs and >0 SBMs/wk and ≥1 of the following: sensation of incomplete evacuation, straining, lumpy hard stools or small pellets for ≥25% of BMsAlvimopan 0.5 mg bid, 1 mg daily or 1 mg bid orally for 6 wk≥3 complete SBMs/wk—4-point scale (no, mild, moderate, or severe straining) with a responder having a mean strainin" @default.
• W2897071318 created "2018-10-26" @default.
• W2897071318 creator A5017722492 @default.
• W2897071318 creator A5021764450 @default.
• W2897071318 creator A5022692391 @default.
• W2897071318 creator A5053195247 @default.
• W2897071318 date "2019-01-01" @default.
• W2897071318 modified "2023-10-14" @default.
• W2897071318 title "American Gastroenterological Association Institute Technical Review on the Medical Management of Opioid-Induced Constipation" @default.
• W2897071318 cites W1581601953 @default.
• W2897071318 cites W1870319372 @default.
• W2897071318 cites W1927728260 @default.
• W2897071318 cites W1966250447 @default.
• W2897071318 cites W1976200263 @default.
• W2897071318 cites W1984091950 @default.
• W2897071318 cites W1996075855 @default.
• W2897071318 cites W2009275234 @default.
• W2897071318 cites W2012125655 @default.
• W2897071318 cites W2015909994 @default.
• W2897071318 cites W2020351580 @default.
• W2897071318 cites W2021543354 @default.
• W2897071318 cites W2021642055 @default.
• W2897071318 cites W2061136386 @default.
• W2897071318 cites W2075798150 @default.
• W2897071318 cites W2097538787 @default.
• W2897071318 cites W2101940977 @default.
• W2897071318 cites W2103154281 @default.
• W2897071318 cites W2105170404 @default.
• W2897071318 cites W2111167091 @default.
• W2897071318 cites W2111430126 @default.
• W2897071318 cites W2114340927 @default.
• W2897071318 cites W2132266888 @default.
• W2897071318 cites W2141082156 @default.
• W2897071318 cites W2141948807 @default.
• W2897071318 cites W2145317305 @default.
• W2897071318 cites W2150884903 @default.
• W2897071318 cites W2156266538 @default.
• W2897071318 cites W2158281754 @default.
• W2897071318 cites W2164341191 @default.
• W2897071318 cites W2165010366 @default.
• W2897071318 cites W2178105433 @default.
• W2897071318 cites W2300634987 @default.
• W2897071318 cites W2334818213 @default.
• W2897071318 cites W2342528407 @default.
• W2897071318 cites W2396215196 @default.
• W2897071318 cites W2402418945 @default.
• W2897071318 cites W2406100280 @default.
• W2897071318 cites W2407927263 @default.
• W2897071318 cites W2472796412 @default.
• W2897071318 cites W2504690161 @default.
• W2897071318 cites W2550361575 @default.
• W2897071318 cites W2554777816 @default.
• W2897071318 cites W2602941024 @default.
• W2897071318 cites W2611714876 @default.
• W2897071318 cites W2616456691 @default.
• W2897071318 cites W2617664403 @default.
• W2897071318 cites W2734740211 @default.
• W2897071318 cites W2739913519 @default.
• W2897071318 cites W2763722121 @default.
• W2897071318 cites W2786188339 @default.
• W2897071318 cites W2792218458 @default.
• W2897071318 cites W2801609795 @default.
• W2897071318 cites W2916021673 @default.
• W2897071318 cites W2977982837 @default.
• W2897071318 doi "https://doi.org/10.1053/j.gastro.2018.08.018" @default.
• W2897071318 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6685294" @default.
• W2897071318 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30337104" @default.
• W2897071318 hasPublicationYear "2019" @default.
• W2897071318 type Work @default.
• W2897071318 sameAs 2897071318 @default.
• W2897071318 citedByCount "34" @default.
• W2897071318 countsByYear W28970713182017 @default.
• W2897071318 countsByYear W28970713182019 @default.
• W2897071318 countsByYear W28970713182020 @default.
• W2897071318 countsByYear W28970713182021 @default.
• W2897071318 countsByYear W28970713182022 @default.
• W2897071318 countsByYear W28970713182023 @default.
• W2897071318 crossrefType "journal-article" @default.
• W2897071318 hasAuthorship W2897071318A5017722492 @default.
• W2897071318 hasAuthorship W2897071318A5021764450 @default.
• W2897071318 hasAuthorship W2897071318A5022692391 @default.
• W2897071318 hasAuthorship W2897071318A5053195247 @default.
• W2897071318 hasBestOaLocation W28970713181 @default.
• W2897071318 hasConcept C126322002 @default.
• W2897071318 hasConcept C142853389 @default.
• W2897071318 hasConcept C15744967 @default.
• W2897071318 hasConcept C170493617 @default.
• W2897071318 hasConcept C2781063702 @default.
• W2897071318 hasConcept C2781112942 @default.
• W2897071318 hasConcept C542102704 @default.
• W2897071318 hasConcept C61434518 @default.
• W2897071318 hasConcept C71924100 @default.
• W2897071318 hasConcept C90924648 @default.
• W2897071318 hasConceptScore W2897071318C126322002 @default.
• W2897071318 hasConceptScore W2897071318C142853389 @default.
• W2897071318 hasConceptScore W2897071318C15744967 @default.
• W2897071318 hasConceptScore W2897071318C170493617 @default.
• W2897071318 hasConceptScore W2897071318C2781063702 @default.

• next