Laxatives Do Not Improve Symptoms of Opioid-Induced Constipation: Results of a Patient Survey

Emmanuel, Anton; Johnson, Martin; McSkimming, Paula; Dickerson, Sara

doi:10.1093/pm/pnw240

Cited by 42 publications

(39 citation statements)

References 22 publications

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“…Nonetheless, in this study, a substantial proportion of patients receiving opioid analgesics experienced OIC despite prophylactic therapy. A potential explanation for this finding is that most prophylactic therapies given were laxatives and, therefore, limited by their lack of specificity for the etiology of OIC . A more robust study is needed to evaluate targeted prophylactic therapies for OIC (eg, PAMORAs) to determine if such treatments have a more pronounced effect in a prophylactic setting.…”

Section: Discussionmentioning

confidence: 99%

Incidence of opioid‐induced constipation in Japanese patients with cancer pain: A prospective observational cohort study

et al. 2019

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This multicenter, prospective, observational cohort study assessed opioid induced constipation (OIC) in Japanese patients with cancer. Eligible patients had stable cancer and an ECOG PS of 0‐2. OIC incidence based on the Rome IV diagnostic criteria was determined by patient diary entries during the first 14 days of opioid therapy. The proportion of patients with OIC was calculated for each 1‐week period and the overall 2‐week study period. Secondary measurements of OIC included the Bowel Function Index (BFI) score (patient assessment administered by physician), spontaneous bowel movements (SBMs) per week (patient assessment), and physician assessments. Medication for constipation was allowed. Two hundred and twenty patients were enrolled. The mean morphine‐equivalent dose was 22 mg/day. By Rome IV criteria, the cumulative incidence of OIC was 56% (95% CI: 49.2%‐62.9%); week 1, 48% (95% CI: 40.8%‐54.6%); week 2, 37% (95% CI: 30.1%‐43.9%). The cumulative incidence of OIC was lower in patients who received prophylactic agents for constipation (48% [95% CI: 38.1%‐57.5%]) than in patients who did not (65% [95% CI: 55.0%‐74.2%]). The cumulative incidences of OIC were 59% (95% CI: 51.9%‐66.0%), 61% (95% CI: 54.3%‐68.1%), and 45% (95% CI: 38.0%‐51.8%) based on BFI scores, physician assessments, and SBM frequency, respectively. Frequency of BMs/week before starting opioids was the most influential factor for the occurrence of OIC. Utilization of prophylactic agents for constipation was associated with a modest effect on reducing the incidence of OIC. The incidences of OIC reported were variable depending on the diagnostic tool involved.

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Section: Discussionmentioning

confidence: 99%

Incidence of opioid‐induced constipation in Japanese patients with cancer pain: A prospective observational cohort study

et al. 2019

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“…Opioids are effective for treating chronic pain in older patients (≥ 65 years of age) [5]; however, evidence suggests the risk of OIC rises with age [6]. In fact, OIC is underrecognized and undertreated in the older population [7], and often does not respond to conventional laxatives [8]. Additionally, studies of nursing home residents show that OIC is associated with worse physical and mental outcomes in older patients [9,10].…”

Section: Introductionmentioning

confidence: 99%

Safety and Efficacy of Naldemedine for the Treatment of Opioid-Induced Constipation in Patients with Chronic Non-Cancer Pain Receiving Opioid Therapy: A Subgroup Analysis of Patients ≥ 65 Years of Age

et al. 2020

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Background Opioid-induced constipation (OIC), the most common side effect of opioid treatment, is under-recognized and undertreated in older patients. Naldemedine, an oral, peripherally acting μ-opioid receptor antagonist (PAMORA), is approved in Japan, the United States, and the European Union for treatment of OIC in adult patients. Objective This integrated analysis of three phase 3 trials (COMPOSE-1, COMPOSE-2, and COMPOSE-3) evaluated the safety and efficacy of naldemedine for up to 12 weeks in a subgroup of patients aged ≥ 65 years. Methods Patients aged 18-80 years with chronic non-cancer pain for ≥ 3 months (treated with opioids for ≥ 3 months in COMPOSE-1 and COMPOSE-2) and OIC received oral naldemedine 0.2 mg or placebo once daily. Safety assessments included overall incidence of treatment-emergent adverse events (TEAEs), TEAEs in the gastrointestinal disorders System Organ Class, and TEAEs of opioid withdrawal or possible opioid withdrawal. Efficacy was based on the proportion of responders in COMPOSE-1 and COMPOSE-2, defined as having ≥ 3 spontaneous bowel movements/week and a ≥ 1-spontaneous bowel movement/week increase from baseline for ≥ 9 of 12 weeks and ≥ 3 of the last 4 weeks. Results A total of 14.8% (344/2328) of patients were aged ≥ 65 years in all studies. The incidence of TEAEs in naldemedinetreated patients aged ≥ 65 years (45.9%) was comparable to that in patients aged ≥ 65 years receiving placebo (51.6%) and in the overall naldemedine group (47.1%). The incidence of gastrointestinal disorders System Organ Class TEAEs in naldemedine-treated patients aged ≥ 65 years (20.2%) was also comparable to that in patients aged ≥ 65 years receiving placebo (16.1%) and in the overall naldemedine group (21.8%). The incidence of TEAEs of opioid withdrawal with naldemedine was 1.1% in patients aged ≥ 65 years and 1.0% overall, and the incidence of TEAEs of possible opioid withdrawal was 1.1% in patients aged ≥ 65 years and 1.7% overall. The proportion of responders was higher in naldemedine-treated patients versus placebo, both overall (50.1% vs 34.1%; p < 0.0001) and in those aged ≥ 65 years (51.8% vs 37.6%). Conclusions This integrated analysis confirmed that OIC treatment with naldemedine 0.2 mg was generally well tolerated and effective in patients aged ≥ 65 years with chronic non-cancer pain. Safety and efficacy results were consistent with the overall patient population. ClinicalTrials.gov registration NCT01965158, NCT01993940, NCT01965652. Key PointsIndividuals aged 65 years or older can safely use naldemedine to treat opioid-induced constipation.Naldemedine is effective in improving symptoms of opioid-induced constipation in adults, regardless of age.Electronic supplementary material The online version of this article (https ://doi.org/10.1007/s4026 6-020-00753 -2) contains supplementary material, which is available to authorized users.Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or nationa...

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“…1,3 Opioid-induced constipation results from the binding of opioids to peripheral μ-opioid receptors in the gastrointestinal tract and is one of the most common adverse opioid reactions for patients receiving opioid analgesics. [5][6][7] Moreover, laxatives are often associated with side effects such as gas and bloating in patients with opioid-induced constipation, which further diminishes patients' quality of life. [5][6][7] Moreover, laxatives are often associated with side effects such as gas and bloating in patients with opioid-induced constipation, which further diminishes patients' quality of life.…”

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confidence: 99%

“…1,4 Laxatives are considered a first-line treatment in patients with opioid-induced constipation; however, their mechanism of action does not treat the underlying cause of opioid-induced constipation, and they are ineffective in >50% of individuals. [5][6][7] Moreover, laxatives are often associated with side effects such as gas and bloating in patients with opioid-induced constipation, which further diminishes patients' quality of life. 6 Naldemedine is an oral peripherally acting μ-opioidreceptor antagonist approved for the treatment of opioid-induced constipation in adults with chronic noncancer pain (United States and Japan) and adults with cancer (Japan).…”

mentioning

confidence: 99%

“…[5][6][7] Moreover, laxatives are often associated with side effects such as gas and bloating in patients with opioid-induced constipation, which further diminishes patients' quality of life. 6 Naldemedine is an oral peripherally acting μ-opioidreceptor antagonist approved for the treatment of opioid-induced constipation in adults with chronic noncancer pain (United States and Japan) and adults with cancer (Japan). 8 Naldemedine minimally crosses the blood-brain barrier and, therefore, effectively treats opioid-induced constipation without negating the analgesic effects of opioid therapy.…”

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confidence: 99%

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The Influence of Renal or Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Naldemedine

Fukumura

Yamada

Yokota

et al. 2019

Clinical Pharm in Drug Dev

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Naldemedine is a peripherally acting μ-opioid-receptor antagonist for the treatment of opioid-induced constipation. Two phase 1 single-dose studies investigated the pharmacokinetics and safety of a 0.2-mg oral dose of naldemedine in subjects with renal impairment (mild, n = 9; moderate, n = 9; severe, n = 6; and end-stage renal disease, n = 8) or hepatic impairment (mild or moderate, n = 8 each) and demographically matched healthy subjects with normal renal and hepatic function (n = 8, both studies). Pharmacokinetic assessments indicate that dose adjustments for naldemedine are not necessary for subjects with any degree of renal impairment or for subjects with mild or moderate hepatic impairment. In subjects with renal impairment compared with healthy subjects with normal renal function, the geometric mean ratios of naldemedine area under the concentration-time curve (AUC 0-inf ) ranged from 82.8% (90%CI 69.5% to 98.6%) to 137.8% (90%CI 114.0% to 166.5%). Renal clearance decreased with reduced renal function (normal function 1.3 L/h; mild impairment 1.1 L/h; moderate impairment 1.0 L/h; severe impairment 0.5 L/h), and only 2.7% of naldemedine was removed by hemodialysis. In subjects with hepatic impairment compared with healthy subjects with normal hepatic function, the geometric mean ratio of AUC 0-inf ranged from 82.8% (90%CI 65.7% to 104.5%) to 105.2% (90%CI 83.4% to 132.6%). Naldemedine was well tolerated in both healthy subjects and subjects with renal or hepatic impairment, and reported adverse events were generally consistent with the known safety profile.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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Laxatives Do Not Improve Symptoms of Opioid-Induced Constipation: Results of a Patient Survey

Cited by 42 publications

References 22 publications

Incidence of opioid‐induced constipation in Japanese patients with cancer pain: A prospective observational cohort study

Incidence of opioid‐induced constipation in Japanese patients with cancer pain: A prospective observational cohort study

Safety and Efficacy of Naldemedine for the Treatment of Opioid-Induced Constipation in Patients with Chronic Non-Cancer Pain Receiving Opioid Therapy: A Subgroup Analysis of Patients ≥ 65 Years of Age

The Influence of Renal or Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Naldemedine

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