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Postgraduate Medicine 2016Constipation is a common adverse effect in patients requiring long-term opioid therapy for pain control. Methylnaltrexone, a quaternary peripheral mu-opioid receptor... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Constipation is a common adverse effect in patients requiring long-term opioid therapy for pain control. Methylnaltrexone, a quaternary peripheral mu-opioid receptor antagonist, is an effective treatment of opioid induced constipation (OIC) without affecting centrally mediated analgesia. Our objective was to conduct a review and meta-analysis to evaluate the efficacy of methylnaltrexone for treatment of OIC, as well as to provide a clinical discussion regarding newly developed alternatives and provide the current treatment algorithm utilized at our institution.
METHODS
We performed a systematic review and meta-analysis of randomized control trials using Cochrane Collaboration Databases and MEDLINE from 2007-present. Literature related to methylnaltrexone, opioids, opioid receptors, opioid antagonists, opioid-induced constipation were reviewed. A meta-analysis was completed with the primary outcome of rescue-free bowel movement (RFBM) within four hours of administration. All pooled analyses were based on random-effects models.
RESULTS
1239 patients were analyzed; 599 received methylnaltrexone and 640 received placebo. With a 95% CI calculated, the true risk difference is between 0.267 and 0.385, demonstrating a statistically significant difference in RFBM between treatment and placebo groups (p < 0.0001). Both the 0.15 mg/kg, 0.30 mg/kg doses every other day, and 12 mg/day dose were found to have increased risk of RFBM compared to placebo.
CONCLUSION
Results support the use of methylnaltrexone. Furthermore, the use of methylnaltrexone to induce laxation may decrease use of health care resources, increase work productivity, and improve cost utilization. New treatments have been made available; however, controlled clinical studies are needed to demonstrate long-term efficacy, safety and cost-effectiveness. Possible limitations of this study include the relatively small number of randomized, placebo-controlled trials investigating the efficacy of methylnaltrexone versus placebo. There is also the possibility of publication bias, which may lead to overestimating the efficacy of methylnaltrexone in treating OIC.
Topics: Analgesics, Opioid; Chronic Pain; Constipation; Humans; Naltrexone; Narcotic Antagonists; Quaternary Ammonium Compounds; Receptors, Opioid, mu; Treatment Outcome
PubMed: 26839023
DOI: 10.1080/00325481.2016.1149017 -
Cancer Treatment Reviews Apr 2024Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and treatment of OIC osmotic (e.g. polyethylene glycol) and stimulant (e.g. bisacodyl) laxatives are widely used. Newer drugs such as the peripherally acting µ-opioid receptor antagonists (PAMORAs) and naloxone in a fixed combination with oxycodone have become available for the management of OIC. This systematic review and meta-analysis aims to give an overview of the scientific evidence on pharmacological strategies for the prevention and treatment of OIC in cancer patients.
METHODS
A systematic search in PubMed, Embase, Web of Science and the Cochrane Library was completed from inception up to 22 October 2022. Randomized and non-randomized studies were systematically selected. Bowel function and adverse drug events were assessed.
RESULTS
Twenty trials (prevention: five RCTs and three cohort studies; treatment: ten RCTs and two comparative cohort studies) were included in the review. Regarding the prevention of OIC, three RCTs compared laxatives with other laxatives, finding no clear differences in effectivity of the laxatives used. One cohort study showed a significant benefit of magnesium oxide compared with no laxative. One RCT found a significant benefit for the PAMORA naldemedine compared with magnesium oxide. Preventive use of oxycodone/naloxone did not show a significant difference in two out of three other studies compared to oxycodone or fentanyl. A meta-analysis was not possible. Regarding the treatment of OIC, two RCTs compared laxatives, of which one RCT found that polyethylene glycol was significantly more effective than sennosides. Seven studies compared an opioid antagonist (naloxone, methylnaltrexone or naldemedine) with placebo and three studies compared different dosages of opioid antagonists. These studies with opioid antagonists were used for the meta-analysis. Oxycodone/naloxone showed a significant improvement in Bowel Function Index compared to oxycodone with laxatives (MD -13.68; 95 % CI -18.38 to -8.98; I = 58 %). Adverse drug event rates were similar amongst both groups, except for nausea in favour of oxycodone/naloxone (RR 0.51; 95 % CI 0.31-0.83; I = 0 %). Naldemedine (NAL) and methylnaltrexone (MNTX) demonstrated significantly higher response rates compared to placebo (NAL: RR 2.07, 95 % CI 1.64-2.61, I = 0 %; MNTX: RR 3.83, 95 % CI 2.81-5.22, I = 0 %). With regard to adverse events, abdominal pain was more present in treatment with methylnaltrexone and diarrhea was significantly more present in treatment with naldemedine. Different dosages of methylnaltrexone were not significantly different with regard to both efficacy and adverse drug event rates.
CONCLUSIONS
Magnesium oxide and naldemedine are most likely effective for prevention of OIC in cancer patients. Naloxone in a fixed combination with oxycodone, naldemedine and methylnaltrexone effectively treat OIC in cancer patients with acceptable adverse events. However, their effect has not been compared to standard (osmotic and stimulant) laxatives. More studies comparing standard laxatives with each other and with opioid antagonists are necessary before recommendations for clinical practice can be made.
Topics: Humans; Laxatives; Analgesics, Opioid; Narcotic Antagonists; Constipation; Oxycodone; Opioid-Induced Constipation; Magnesium Oxide; Cohort Studies; Naloxone; Polyethylene Glycols; Neoplasms; Drug-Related Side Effects and Adverse Reactions; Quaternary Ammonium Compounds; Naltrexone
PubMed: 38452708
DOI: 10.1016/j.ctrv.2024.102704 -
Neurogastroenterology and Motility Dec 2023Constipation is frequent in critically ill patients, and potentially related to adverse outcomes. Peripherally-active mu-opioid receptor antagonists (PAMORAs) are... (Meta-Analysis)
Meta-Analysis
Peripherally-active mu-opioid receptor antagonists for constipation in critically ill patients receiving opioids: A case-series and a systematic review and meta-analysis of the literature.
BACKGROUND
Constipation is frequent in critically ill patients, and potentially related to adverse outcomes. Peripherally-active mu-opioid receptor antagonists (PAMORAs) are approved for opioid-induced constipation, but information on their efficacy and safety in critically ill patients is limited. We present a single-center, retrospective, case-series of the use of naldemedine for opioid-associated constipation, and we systematically reviewed the use of PAMORAs in critically ill patients.
METHODS
Case-series included consecutive mechanically-ventilated patients; constipation was defined as absence of bowel movements for >3 days. Naldemedine was administered after failure of the local laxation protocol. Systematic review: PubMed was searched for studies of PAMORAs to treat opioid-induced constipation in adult critically ill patients.
PRIMARY OUTCOMES
time to laxation, and number of patients laxating at the shortest follow-up.
SECONDARY OUTCOMES
gastric residual volumes and adverse events.
KEY RESULTS
A total of 13 patients were included in the case-series; the most common diagnosis was COVID-19 ARDS. Patients had their first bowel movement 1 [0;2] day after naldemedine. Daily gastric residual volume was 725 [405;1805] before vs. 250 [45;1090] mL after naldemedine, p = 0.0078. Systematic review identified nine studies (two RCTs, one prospective case-series, three retrospective case-series and three case-reports). Outcomes were similar between groups, with a trend toward a lower gastric residual volume in PAMORAs group.
CONCLUSIONS & INFERENCES
In a highly-selected case-series of patients with refractory, opioid-associated constipation, naldemedine was safe and associated to reduced gastric residuals and promoting laxation. In the systematic review and meta-analysis, the use of PAMORAs (mainly methylnaltrexone) was safe and associated with a reduced intolerance to enteral feeding but no difference in the time to laxation.
Topics: Adult; Humans; Narcotic Antagonists; Analgesics, Opioid; Constipation; Opioid-Induced Constipation; Retrospective Studies; Critical Illness; Naltrexone; Laxatives
PubMed: 37869768
DOI: 10.1111/nmo.14694 -
Oncology Nursing Forum Nov 2020A systematic review and meta-analysis was conducted to inform the development of national clinical practice guidelines on the management of cancer constipation. (Meta-Analysis)
Meta-Analysis
PROBLEM IDENTIFICATION
A systematic review and meta-analysis was conducted to inform the development of national clinical practice guidelines on the management of cancer constipation.
LITERATURE SEARCH
PubMed®, Wiley Cochrane Library, and CINAHL® were searched for studies published from May 2009 to May 2019.
DATA EVALUATION
Two investigators independently reviewed and extracted data from eligible studies. The Cochrane Collaboration risk-of-bias tool was used, and the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to assess the certainty of the evidence.
SYNTHESIS
For patients with cancer and opioid-induced constipation, moderate benefit was found for osmotic or stimulant laxatives; small benefit was found for methylnaltrexone, naldemedine, and electroacupuncture. For patients with cancer and non-opioid-related constipation, moderate benefit was found for naloxegol, prucalopride, lubiprostone, and linaclotide; trivial benefit was found for acupuncture.
IMPLICATIONS FOR PRACTICE
Effective strategies for managing opioid-induced and non-opioid-related constipation in patients with cancer include lifestyle, pharmacologic, and complementary approaches.
SUPPLEMENTAL MATERIAL CAN BE FOUND AT&NBSP;HTTPS
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Topics: Analgesics, Opioid; Constipation; Gastrointestinal Agents; Humans; Neoplasms
PubMed: 33063777
DOI: 10.1188/20.ONF.E211-E224 -
Expert Opinion on Pharmacotherapy Mar 2015Opioid-induced constipation (OIC) is one of the most frequent and burdening adverse events (AE) of opioid therapy. This systematic review aimed to evaluate efficacy and... (Review)
Review
INTRODUCTION
Opioid-induced constipation (OIC) is one of the most frequent and burdening adverse events (AE) of opioid therapy. This systematic review aimed to evaluate efficacy and safety of drugs in randomized controlled trials (RCTs) with adult OIC patients.
AREAS COVERED
Efficacy assessment focused on objective outcome measures (OOMs): bowel movement (BM) frequency, BM within 4 h and time to first BM. Twenty-one studies examining seven drugs were identified. Methylnaltrexone showed improvements in all three OOMs. RCTs in naloxone and alvimopan tended to be effective for BM frequency measures. Naloxegol (≥ 12.5 mg) improved all OOMs. Though effectiveness of lubiprostone was demonstrated for all OOMs, group differences were small to moderate. CB-5945 and prucalopride tended to increase BM frequency, especially for 0.1 mg twice daily and 4 mg daily, respectively. Besides nausea and diarrhea, abdominal pain was the most frequent AE for all drugs (risk ratio, range: 1.52 - 5.06) except for alvimopan. Treatment-related serious AEs were slightly higher for alvimopan (cardiac events) and prucalopride (severe abdominal pain, headache). Pain scores for placebo and intervention groups were similar for all drugs.
EXPERT OPINION
Finding a consensus definition and inclusion criteria for OIC plus a rational balance between efficacy and AEs of drugs remain future challenges.
Topics: Abdominal Pain; Analgesics, Opioid; Constipation; Diarrhea; Gastrointestinal Motility; Headache; Humans; Nausea; Pain; Randomized Controlled Trials as Topic
PubMed: 25539282
DOI: 10.1517/14656566.2015.995625 -
The Cochrane Database of Systematic... May 2015This article describes the second update of a Cochrane review on the effectiveness of laxatives for the management of constipation in people receiving palliative care.... (Review)
Review
BACKGROUND
This article describes the second update of a Cochrane review on the effectiveness of laxatives for the management of constipation in people receiving palliative care. Previous versions were published in 2006 and 2010 where we also evaluated trials of methylnaltrexone; these trials have been removed as they are included in another review in press. In these earlier versions, we drew no conclusions on individual effectiveness of different laxatives because of the limited number of evaluations. This is despite constipation being common in palliative care, generating considerable suffering due to the unpleasant physical symptoms and the availability of a wide range of laxatives with known differences in effect in other populations.
OBJECTIVES
To determine the effectiveness and differential efficacy of laxatives used to manage constipation in people receiving palliative care.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library), MEDLINE, EMBASE, CINAHL and Web of Science (SCI & CPCI-S) for trials to September 2014.
SELECTION CRITERIA
Randomised controlled trials (RCTs) evaluating laxatives for constipation in people receiving palliative care.
DATA COLLECTION AND ANALYSIS
Two authors assessed trial quality and extracted data. The appropriateness of combining data from the studies depended upon clinical and outcome measure homogeneity.
MAIN RESULTS
We identified five studies involving the laxatives lactulose, senna, co-danthramer, misrakasneham, docusate and magnesium hydroxide with liquid paraffin. Overall, the study findings were at an unclear risk of bias. As all five studies compared different laxatives or combinations of laxatives, it was not possible to perform a meta-analysis. There was no evidence on whether individual laxatives were more effective than others or caused fewer adverse effects.
AUTHORS' CONCLUSIONS
This second update found that laxatives were of similar effectiveness but the evidence remains limited due to insufficient data from a few small RCTs. None of the studies evaluated polyethylene glycol or any intervention given rectally. There is a need for more trials to evaluate the effectiveness of laxatives in palliative care populations. Extrapolating findings on the effectiveness of laxatives evaluated in other populations should proceed with caution. This is because of the differences inherent in people receiving palliative care that may impact, in a likely negative way, on the effect of a laxative.
Topics: Analgesics, Opioid; Anthraquinones; Cathartics; Constipation; Humans; Lactulose; Magnesium Hydroxide; Naltrexone; Palliative Care; Paraffin; Quaternary Ammonium Compounds; Randomized Controlled Trials as Topic; Senna Extract
PubMed: 25967924
DOI: 10.1002/14651858.CD003448.pub4 -
Alimentary Pharmacology & Therapeutics Jul 2020When opioid-induced constipation is treated with centrally acting opioid antagonists, there may be opioid withdrawal or aggravation of pain due to inhibition of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
When opioid-induced constipation is treated with centrally acting opioid antagonists, there may be opioid withdrawal or aggravation of pain due to inhibition of μ-opioid analgesia. This led to the development of peripherally acting μ-opioid receptor antagonists (PAMORAs).
AIM
To evaluate the efficacy of available PAMORAs and other approved or experimental treatments for relieving constipation in patients with opioid-induced constipation, based on a systematic review and meta-analysis of published studies.
METHODS
A search of MEDLINE, EMBASE and EBM Reviews Cochrane Central Register of Controlled Trials was completed in July 2019 for randomised trials compared to placebo. FDA approved doses or highest studied dose was evaluated. Efficacy was based on diverse endpoints, including continuous variables (the bowel function index, number of spontaneous bowel movements and stool consistency based on Bristol Stool Form Scale), or responder analysis (combination of >3 spontaneous bowel movements or complete spontaneous bowel movements plus 1 spontaneous bowel movement or complete spontaneous bowel movements, respectively, over baseline [so-called FDA endpoints]). Adverse effects evaluated included central opioid withdrawal, serious adverse events, abdominal pain and diarrhoea.
RESULTS
We included 35 trials at low risk of bias enrolling 13 566 patients. All PAMORAs demonstrated efficacy on diverse patient response endpoints. There was greater efficacy with approved doses of the PAMORAs (methylnaltrexone, naloxegol and naldemidine), with lower efficacy or lower efficacy and greater adverse effects with combination oxycodone with naloxone, lubiprostone and linaclotide.
CONCLUSIONS
Therapeutic response in opioid-induced constipation is best achieved with the PAMORAs, methylnaltrexone, naloxegol and naldemidine, which are associated with low risk of serious adverse events.
Topics: Analgesics, Opioid; Constipation; Humans; Laxatives; Narcotic Antagonists; Randomized Controlled Trials as Topic; Receptors, Opioid, mu; Treatment Outcome
PubMed: 32462777
DOI: 10.1111/apt.15791 -
Clinical Gastroenterology and... Oct 2018Opioid-induced constipation (OIC) is a common problem in patients on chronic opioid therapy for cancer-related and non-cancer-related pain. Approved treatments for OIC... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Opioid-induced constipation (OIC) is a common problem in patients on chronic opioid therapy for cancer-related and non-cancer-related pain. Approved treatments for OIC are methylnaltrexone, naloxone, naloxegol, alvimopan, naldemedine, and lubiprostone. Since a meta-analysis performed in 2014, 2 new agents have been approved by the Food and Drug Administration for treatment of OIC (naloxegol and naldemedine).
METHODS
We conducted a search of the medical literature following the protocol outlined in the Cochrane Handbook for systematic review. We searched MEDLINE, EMBASE, EMBASE Classic, Web of Science, and the Cochrane Central Register of Controlled Trials until March 2017 to identify randomized controlled trials of peripheral μ-opioid-receptor antagonists (methylnaltrexone, naloxone, naloxegol, alvimopan, axelopran, or naldemedine), lubiprostone, or prucalopride. Response to therapy was extracted in a dichotomous assessment as an overall response to therapy. The effect of pharmacologic therapies was pooled and reported as a relative risk (RR) of failure to respond to the treatment drug, with 95% CIs.
RESULTS
We included 27 placebo-controlled trials in our meta-analysis (23 trials evaluated μ-opioid-receptor antagonists, 3 trials evaluated lubiprostone, and 1 trial evaluated prucalopride). In these trials, 5390 patients received a drug and 3491 received a placebo. Overall, μ-opioid-receptor antagonists, lubiprostone, and prucalopride were superior to placebo for the treatment of OIC, with a RR of failure to respond to therapy of 0.70 (95% CI, 0.64-0.75) and an overall number needed to treat of 5 (95% CI, 4-7). When restricted to only Food and Drug Administration-approved medications for OIC, the RR of failure to respond to therapy was 0.69 (95% CI, 0.62-0.77), with a number needed to treat of 5 (95% CI, 4-7). Sensitivity analyses and meta-regression performed to account for heterogeneity showed that treatment was more likely to be effective in study populations taking higher doses of opiates at baseline or refractory to laxatives. Study duration and prespecified primary outcome did not affect the RR of failure. Participants who received μ-opioid-receptor antagonists were significantly more likely to have diarrhea, abdominal pain, nausea, or vomiting than patients who received placebo.
CONCLUSIONS
In a systematic review and meta-analysis, we found μ-opioid-receptor antagonists to be safe and effective for the treatment of OIC. Prescription-strength laxatives (prucalopride, lubiprostone) are slightly better than placebo in reducing OIC.
Topics: Analgesics, Opioid; Constipation; Female; Gastrointestinal Agents; Humans; Male; Narcotic Antagonists; Randomized Controlled Trials as Topic; Receptors, Opioid, mu; Treatment Outcome
PubMed: 29374616
DOI: 10.1016/j.cgh.2018.01.021 -
The Cochrane Database of Systematic... Sep 2022Opioid-induced bowel dysfunction (OIBD) is characterised by constipation, incomplete evacuation, bloating, and gastric reflux. It is one of the major adverse events... (Review)
Review
BACKGROUND
Opioid-induced bowel dysfunction (OIBD) is characterised by constipation, incomplete evacuation, bloating, and gastric reflux. It is one of the major adverse events (AEs) of treatment for pain in cancer and palliative care, resulting in increased morbidity and reduced quality of life. This review is a partial update of a 2008 review, and critiques as previous update (2018) trials only for people with cancer and people receiving palliative care.
OBJECTIVES
To assess for OIBD in people with cancer and people receiving palliative care the effectiveness and safety of mu-opioid antagonists (MOAs) versus different doses of MOAs, alternative pharmacological/non-pharmacological interventions, placebo, or no treatment.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science (December 2021), clinical trial registries and regulatory websites. We sought contact with MOA manufacturers for further data.
SELECTION CRITERIA
Randomised controlled trials (RCTs) assessing the effectiveness and safety of MOAs for OIBD in people with cancer and people at a palliative stage irrespective of the type of terminal disease.
DATA COLLECTION AND ANALYSIS
Two review authors assessed risk of bias and extracted data. The appropriateness of combining data from the trials depended upon sufficient homogeneity across trials. Our primary outcomes were laxation response, effect on analgesia, and AEs. We assessed the certainty of evidence using GRADE and created summary of findings tables.
MAIN RESULTS
We included 10 studies (two new trials) randomising in-total 1343 adults with cancer irrespective of stage, or at palliative care stage of any disease. The MOAs were oral naldemedine and naloxone (alone or in combination with oxycodone), and subcutaneous methylnaltrexone. The trials compared MOAs with placebo, MOAs at different doses, or in combination with other drugs. Two trials of naldemedine and three of naloxone with oxycodone were in people with cancer irrespective of disease stage. The trial on naloxone alone was in people with advanced cancer. Four trials on methylnaltrexone were in palliative care where most participants had advanced cancer. All trials were vulnerable to biases; most commonly, blinding of the outcome assessor was not reported. Oral naldemedine versus placebo Risk (i.e. chance) of spontaneous laxations in the medium term (over two weeks) for naldemedine was over threefold greater risk ratio (RR) 2.00, 95% confidence interval (CI) 1.59 to 2.52, 2 trials, 418 participants, I² = 0%. Number needed to treat for an additional beneficial outcome (NNTB) 3, 95% CI 3 to 4; moderate-certainty evidence). Earlier risk of spontaneous laxations and patient assessment of bowel change was not reported. Very low-certainty evidence showed naldemedine had little to no effect on opioid withdrawal symptoms. There was little to no difference in the risk of serious (non-fatal) AEs (RR 3.34, 95% CI 0.85 to 13.15: low-certainty evidence). Over double the risk of AEs (non-serious) reported with naldemedine (moderate-certainty evidence). Low-dose oral naldemedine versus higher dose Risk of spontaneous laxations was lower for the lower dose (medium term, 0.1 mg versus 0.4 mg: RR 0.69, 95% CI 0.53 to 0.89, 1 trial, 111 participants (low-certainty evidence)). Earlier risk of spontaneous laxations and patient assessment of bowel change not reported. Low-certainty evidence showed little to no difference on opioid withdrawal symptoms (0.1 mg versus 0.4 mg mean difference (MD) -0.30, 95% CI -0.85 to 0.25), and occurrences of serious AEs (0.1 mg versus 0.4 mg RR 0.25, 95% CI 0.03 to 2.17). Low-certainty evidence showed little to no difference on non-serious AEs. Oral naloxone versus placebo Risk of spontaneous laxations and AEs not reported. Little to no difference in pain intensity (very low-certainty evidence). Full data not given. The trial reported that no serious AEs occurred. Oral naloxone + oxycodone versus oxycodone Risk of spontaneous laxations within 24 hours and in the medium term not reported. Low-certainty evidence showed naloxone with oxycodone reduced the risk of opioid withdrawal symptoms. There was little to no difference in the risk of serious (non-fatal) AEs (RR 0.68, 95% CI 0.44 to 1.06), 3 trials, 362 participants, I² = 55%: very low-certainty evidence). There was little to no difference in risk of AEs (low-certainty evidence). Subcutaneous methylnaltrexone versus placebo Risk of spontaneous laxations within 24 hours with methylnaltrexone was fourfold greater than placebo (RR 2.97, 95% CI 2.13 to 4.13. 2 trials, 287 participants, I² = 31%. NNTB 3, 95% CI 2 to 3; low-certainty evidence). Risk of spontaneous laxations in the medium term was over tenfold greater with methylnaltrexone (RR 8.15, 95% CI 4.76 to 13.95, 2 trials, 305 participants, I² = 47%. NNTB 2, 95% CI 2 to 2; moderate-certainty evidence). Low-certainty evidence showed methylnaltrexone reduced the risk of opioid withdrawal symptoms, and did not increase risk of a serious AE (RR 0.59, 95% CI 0.38 to 0.93. I² = 0%; 2 trials, 364 participants). The risk of AEs was higher for methylnaltrexone (low-certainty evidence). Lower-dose subcutaneous methylnaltrexone versus higher dose There was little to no difference in risk of spontaneous laxations in the medium-term (1 mg versus 5 mg or greater: RR 2.91, 95% CI 0.82 to 10.39; 1 trial, 26 participants very low-certainty evidence), or in patient assessment of improvement in bowel status (RR 0.98, 95% CI 0.71 to 1.35, 1 trial, 102 participants; low-certainty evidence). Medium-term assessment of spontaneous laxations and serious AEs not reported. There was little to no difference in symptoms of opioid withdrawal (MD -0.25, 95% CI -0.84 to 0.34, 1 trial, 102 participants) or occurrence of AEs (low-certainty evidence).
AUTHORS' CONCLUSIONS
This update's findings for naldemedine and naloxone with oxycodone have been strengthened with two new trials, but conclusions have not changed. Moderate-certainty evidence for oral naldemedine on risk of spontaneous laxations and non-serious AEs suggests in people with cancer that naldemedine may improve bowel function over two weeks and increase the risk of AEs. There was low-certainty evidence on serious AEs. Moderate-certainty evidence for methylnaltrexone on spontaneous laxations over two weeks suggests subcutaneous methylnaltrexone may improve bowel function in people receiving palliative care, but certainty of evidence for AEs was low. More trials are needed, more evaluation of AEs, outcomes patients rate as important, and in children.
Topics: Adult; Analgesics, Opioid; Child; Humans; Naloxone; Naltrexone; Narcotic Antagonists; Neoplasms; Opioid-Induced Constipation; Oxycodone; Palliative Care; Quaternary Ammonium Compounds; Substance Withdrawal Syndrome
PubMed: 36106667
DOI: 10.1002/14651858.CD006332.pub4 -
Regional Anesthesia and Pain Medicine 2017Opioid-induced constipation has a negative impact on quality of life for patients with chronic pain and can affect more than a third of patients. A related but separate... (Review)
Review
Opioid-induced constipation has a negative impact on quality of life for patients with chronic pain and can affect more than a third of patients. A related but separate entity is postoperative ileus, which is an abnormal pattern of gastrointestinal motility after surgery. Nonselective μ-opioid receptor antagonists reverse constipation and opioid-induced ileus but cross the blood-brain barrier and may reverse analgesia. Peripherally acting μ-opioid receptor antagonists target the μ-opioid receptor without reversing analgesia. Three such agents are US Food and Drug Administration approved. We reviewed the literature for randomized controlled trials that studied the efficacy of alvimopan, methylnaltrexone, and naloxegol in treating either opioid-induced constipation or postoperative ileus. Peripherally acting μ-opioid receptor antagonists may be effective in treating both opioid-induced bowel dysfunction and postoperative ileus, but definitive conclusions are not possible because of study inconsistency and the relatively low quality of evidence. Comparisons of agents are difficult because of heterogeneous end points and no head-to-head studies.
Topics: Analgesics, Opioid; Constipation; Humans; Ileus; Narcotic Antagonists; Postoperative Complications; Randomized Controlled Trials as Topic
PubMed: 29016552
DOI: 10.1097/AAP.0000000000000671