Combating Opioid-Induced Constipation: New and Emerging Therapies (original) (raw)
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PM & R : the journal of injury, function, and rehabilitation, 2017
Opioid-induced constipation (OIC) is a common side effect of opioid use and can occur from the outset of opioid therapy (Online access: http://courses.elseviercme.com/aapmr2016/638e). OIC has been reported to interfere with pain management, increase health care costs, decrease work productivity and daily activities, and significantly affect patient quality of life. It can also lead to bowel obstruction. Assessing and managing OIC is important for establishing maximum function for patients. Several pharmacologic approaches, with different mechanisms of action, are available or in development.
Opioid-induced constipation: a narrative review of therapeutic options in clinical management
The Korean Journal of Pain
Pain therapy often entails gastrointestinal adverse events. While opioids are effective drugs for pain relief, the incidence of opioid-induced constipation (OIC) varies greatly from 15% to as high as 81%. This can lead to a significant impairment in quality of life, often resulting in discontinuation of opioid therapy. In this regard, a good doctor-patient relationship is especially pivotal when initiating opioid therapy. In addition to a detailed history of bowel habits, patient education regarding the possible gastrointestinal side effects of the drugs is crucial. In addition, the bowel function must be regularly evaluated for the entire duration of treatment with opioids. Furthermore, if the patient has preexisting constipation that is well under control, continuation of that treatment is important. In the absence of such history, general recommendations should include sufficient fluid intake, physical activity, and regular intake of dietary fiber. In patients of OIC with ongoing opioid therapy, the necessity of opioid use should be critically reevaluated in terms of an with acceptable quality of life, particularly in cases of non-cancer pain. If opioids must be continued, lowering the dose may help, as well as changing the type of opioid. If these measures do not suffice, the next step for persistent OIC is the administration of laxatives. If these are ineffective as well, treatment with peripherally active -opioid receptor antagonists should be considered. Enemas and irrigation are emergency measures, often used as a last resort.
Constipation: opioid antagonists in people prescribed opioids
PubMed, 2015
Introduction: Constipation is a common adverse effect of opioids. As an example, constipation is reported in 52% of people with advanced malignancy, and this figure rises to 87% in people who are terminally ill and taking opioids. There is no reason to believe that people with chronic non-malignant disease who are prescribed opioids will be any less troubled by this adverse effect. Methods and outcomes: We conducted a systematic overview and aimed to answer the following clinical question: What are the effects of opioid antagonists for constipation in people prescribed opioids? The population we studied included people with any condition, although most studies were in people with cancer pain. We searched Medline, Embase, The Cochrane Library, and other important databases up to May 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). Results: At this update, searching of electronic databases retrieved 162 studies. After deduplication and removal of conference abstracts, 84 records were screened for inclusion in the review. Appraisal of titles and abstracts led to the exclusion of 47 studies and the further review of 37 full publications. Of the 37 full articles evaluated, two systematic reviews and one RCT were included at this update. We performed a GRADE evaluation for three PICO combinations. Conclusions: In this systematic overview we categorised the efficacy for three interventions based on information relating to the effectiveness of alvimopan, methylnaltrexone, and naloxone.
Opioid-Induced Constipation and Bowel Dysfunction: A Clinical Guideline
Pain Medicine, 2016
Objective. To formulate timely evidence-based guidelines for the management of opioid-induced bowel dysfunction. Setting. Constipation is a major untoward effect of opioids. Increasing prescription of opioids has correlated to increased incidence of opioid-induced constipation. However, the inhibitory effects of opioids are not confined to the colon, but also affect higher segments of the gastrointestinal tract, leading to the coining of the term "opioid-induced bowel dysfunction." Methods. A literature search was conducted using Medline, EMBASE, and EMBASE Classic, and the Cochrane Central Register of Controlled Trials. Predefined search terms and inclusion/exclusion criteria were used to identify and categorize relevant papers. A series of statements were formulated and justified by a comment, then labeled with the degree of agreement and their level of evidence as judged by the Strength of Recommendation Taxonomy (SORT) system. Results. From a list of 10,832 potentially relevant studies, 33 citations were identified for review. Screening the reference lists of the pertinent papers identified additional publications. Current definitions, prevalence, and mechanism of opioidinduced bowel dysfunction were reviewed, and a treatment algorithm and statements regarding patient management were developed to provide
Consensus Recommendations on Initiating Prescription Therapies for Opioid-Induced Constipation
Pain medicine (Malden, Mass.), 2015
Aims of this consensus panel were to determine (1) an optimal symptom-based method for assessing opioid-induced constipation in clinical practice and (2) a threshold of symptom severity to prompt consideration of prescription therapy. A multidisciplinary panel of 10 experts with extensive knowledge/experience with opioid-associated adverse events convened to discuss the literature on assessment methods used for opioid-induced constipation and reach consensus on each objective using the nominal group technique. Five validated assessment tools were evaluated: the Patient Assessment of Constipation-Symptoms (PAC-SYM), Patient Assessment of Constipation-Quality of Life (PAC-QOL), Stool Symptom Screener (SSS), Bowel Function Index (BFI), and Bowel Function Diary (BF-Diary). The 3-item BFI and 4-item SSS, both clinician administered, are the shortest tools. In published trials, the BFI and 12-item PAC-SYM are most commonly used. The 11-item BF-Diary is highly relevant in opioid-induced co...
Neurogastroenterology & Motility, 2014
CONFLICTS OF INTEREST MC has served as an advisory board member and a consultant for AstraZeneca and Theravance, and as an adjudication committee member for AstraZeneca. MC's institution has received fees for his participation as an editorial board member for AstraZeneca and as a consultant for Theravance. DAD has served as an advisory board member for Ironwood Pharmaceuticals, Lexicon Pharmaceuticals, and Synergy Pharmaceuticals; a consultant for AstraZeneca, Ironwood Pharmaceuticals, Ono Pharmaceuticals, and Takeda; has received grant support from AstraZeneca and Ironwood Pharmaceuticals; and currently is President of the Rome Foundation. GB has served as an advisory board member for AstraZeneca, has received speaking fees from Cephalon, Grunenthal, Mundipharma, and Pfizer, and has received clinical research grants from Grunenthal, Mundipharma, Pfizer, and Roche. GB is supported by grants from the Federal Ministry of Education and Research in Germany, the German Cancer Aid and the Ministry of Science and Arts in the federal state of Baden-Wuerttemberg. LRW has served as an advisory board member for
Optimal treatment of opioid induced constipation in daily clinical practice – an observational study
BMC Palliative Care
Background: Opioids are prescribed in over 40% of patients with advanced cancer, but side effects occur frequently. In this study we evaluated the development and treatment of opioid induced constipation (OIC), and OIC resolving effect of methylnaltrexone for different opioid subtypes in daily clinical practice. Methods: Patients with cancer using opioids were included in a retrospective chart analysis. Baseline characteristics, data on opioid use, laxative use, and OIC were collected. Patients with OIC who were prescribed methylnaltrexone, were included in a prospective observational trial (NCT01955213). Results: Thirty-nine of 327 patients (pts) with cancer who were treated with opioids suffered from OIC (overall prevalence 12%; 95%-CI: 8-15%). The prevalence of OIC was similar in patients treated with oxycodone or fentanyl (12 of 81 pts. vs. 18 of 110 pts., RR 0.9; 95%CI 0.4-2.0). The morphine equivalent daily dose did not significantly differ between opioid subtypes (fentanyl 89 mg (IQR 60-180) vs. oxycodone 40 mg (40-80), P = 0.231). Twenty-two individual patients (7%) were admitted for OIC. Most effective laxatives in admitted patients were enemas, methylnaltrexone, or 4-l polyethylene-glycol solution. In the prospective observational study, the effect of methylnaltrexone could be evaluated in 23 patients. Eleven patients achieved the primary endpoint of ≥2 laxation responses out of the first four doses methylnaltrexone, independent of opioid subtype. Conclusions: OIC is a burdensome clinical problem independent of opioid subtype. Timely intensification of prophylactic laxative treatment, especially when opioid doses increase, may help to prevent OIC. Clinically overt OIC requires a more intensive laxative regimen with for example methylnaltrexone. Trial registration: NCT01955213.
The American journal of gastroenterology, 2013
There has been no definitive synthesis of the evidence for any benefit of available pharmacological therapies in opioid-induced constipation (OIC). We conducted a systematic review and meta-analysis to address this deficit. We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials through to December 2012 to identify placebo-controlled trials of μ-opioid receptor antagonists, prucalopride, lubiprostone, and linaclotide in the treatment of adults with OIC. No minimum duration of therapy was required. Trials had to report a dichotomous assessment of overall response to therapy, and data were pooled using a random effects model. Effect of pharmacological therapies was reported as relative risk (RR) of failure to respond to therapy, with 95% confidence intervals (CIs). Fourteen eligible randomized controlled trials (RCTs) of μ-opioid receptor antagonists, containing 4,101 patients, were identified. These were superior to placebo for the treatmen...