Naloxegol 12.5mg tablets

ObjectivesOpioid analgesics may be associated with chronic adverse effects, such as opioid-induced constipation (OIC). Available and emerging prescription medications for OIC in patients with chronic noncancer pain are described, including concerns and challenges associated with OIC management.MethodsNarrative review.ResultsOIC is characterized by a change in bowel habits and defecation patterns that occurs when initiating opioid therapy and is associated with reduced bowel frequency, straining, sensation of incomplete evacuation, and/or patient distress related to bowel habits. Prescription medications are indicated when OIC persists despite conservative approaches (eg, increased fiber and fluid intake, exercise, over-the-counter laxatives and stool softeners). Phase 3 studies have demonstrated the efficacy of peripherally acting µ-opioid receptor antagonists (PAMORA; methylnaltrexone, naloxegol, naldemedine), and a chloride channel activator (lubiprostone) for improving OIC in patients with chronic noncancer pain. Although head-to-head studies are lacking, a meta-analysis demonstrated that μ-opioid receptor antagonists were more effective than placebo for the treatment of OIC. The most common adverse effects associated with prescription medications for OIC are gastrointestinal related (eg, nausea, diarrhea, abdominal pain, or distention), with most being mild or moderate in severity. Therapy currently in development for OIC includes the PAMORA axelopran.DiscussionHealth care providers should be aware of this complication in patients receiving opioids and should monitor and address constipation-related symptoms to optimize pain management and improve patient quality of life.

Abstract licence: CC BY-NC-ND

SummaryBackgroundOpioid‐induced constipation (OIC) is a common adverse effect of opioid therapy.AimTo evaluate the long‐term safety and tolerability of naloxegol, an oral, peripherally acting μ‐opioid receptor antagonist (PAMORA), in patients with noncancer pain and OIC.MethodsA 52‐week, multicenter, open‐label, randomised, parallel‐group phase 3 study was conducted in out‐patients taking 30–1000 morphine‐equivalent units per day for ≥4 weeks. Patients were randomised 2:1 to receive naloxegol 25 mg/day or usual‐care (UC; investigator‐chosen laxative regimen) treatment for OIC.ResultsThe safety set comprised 804 patients (naloxegol, n = 534; UC, n = 270). Mean exposure duration was 268 days with naloxegol and 297 days with UC. Frequency of adverse events (AEs) was 81.8% with naloxegol and 72.2% with UC. Treatment‐emergent AEs occurring more frequently for naloxegol vs. UC were abdominal pain (17.8% vs. 3.3%), diarrhoea (12.9% vs. 5.9%), nausea (9.4% vs. 4.1%), headache (9.0% vs. 4.8%), flatulence (6.9% vs. 1.1%) and upper abdominal pain (5.1% vs. 1.1%). Most naloxegol‐emergent gastrointestinal AEs occurred early, resolving during or after naloxegol discontinuation and were mild or moderate in severity; 11 patients discontinued due to diarrhoea and nine patients owing to abdominal pain. Pain scores and mean daily opioid doses remained stable throughout the study; no attributable opioid withdrawal AEs were observed. Two patients in each group had an adjudicated major adverse cardiovascular event unrelated to study drug; no AEs were reported nor adjudicated as bowel perforations.ConclusionIn patients with noncancer pain and opioid‐induced constipation, naloxegol 25 mg/day up to 52 weeks was generally safe and well tolerated.

Abstract licence: CC BY-NC-ND 3.0

Background Constipation is frequent in critically ill adults receiving opioids. Naloxegol (N), a peripherally acting mu-receptor antagonist (PAMORA), may reduce constipation. The objective of this trial was to evaluate the efficacy and safety of N to prevent constipation in ICU adults receiving opioids. Methods and Patients. In this single-center, double-blind, randomized trial, adults admitted to a medical ICU receiving IV opioids (≥100 mcg fentanyl/day), and not having any of 17 exclusion criteria, were randomized to N (25 mg) or placebo (P) daily randomized to receive N (25mg) or placebo (P) and docusate 100 mg twice daily until ICU discharge, 10 days, or diarrhea (≥3 spontaneous bowel movement (SBM)/24 hours) or a serious adverse event related to study medication. A 4-step laxative protocol was initiated when there was no SBM ≥3 days. Results Only 318 (20.6%) of the 1542 screened adults during the 1/17–10/19 enrolment period met all inclusion criteria. Of these, only 19/381 (4.9%) met all eligibility criteria. After 7 consent refusals, 12 patients were randomized. The study was stopped early due to enrolment futility. The N (n = 6) and P (n = 6) groups were similar. The time to first SBM (N 41.4 ± 31.7 vs. P 32.5 ± 25.4 hours, P = 0.56) was similar. The maximal daily abdominal pressure was significantly lower in the N group (N 10 ± 4 vs. P 13 ± 5, P = 0.002). The median (IQR) daily SOFA scores were higher in N (N 7 (4, 8) vs. P 4 (3, 5), P < 0.001). Laxative protocol use was similar (N 83.3% vs. P 66.6%; P = 0.51). Diarrhea prevalence was high but similar (N 66.6% vs. P 66.6%; P = 1.0). No patient experienced opioid withdrawal. Conclusions Important recruitment challenges exist for ICU trials evaluating the use of PAMORAs for constipation prevention. Despite being underpowered, our results suggest time to first SBM with naloxegol, if different than P, may be small. The effect of naloxegol on abdominal pressure, SOFA, and the interaction between the two requires further research.

Abstract licence: CC BY 4.0

Background: Naloxegol antagonizes peripheral opioid-related side effects without preventing opioid-related analgesia. However, the effect of naloxegol on opioid-induced bladder dysfunction remains unknown. Hypothesis: patients given naloxegol have lower residual bladder urine volume than those given placebo. Methods: 136 patients scheduled for elective hip and knee surgery were randomized to oral naloxegol or placebo given the morning of surgery, and on the first two postoperative mornings. Residual urine volume was measured ultrasonographically within 30 min after voiding once in the morning and once in the afternoon for two postoperative days. Opioid-related Symptom Distress Scale (ORSDS), the need for indwelling urinary catheterization, and quality of recovery (QoR) score were secondary outcomes. Results: 67 were randomized to naloxegol and 64 to placebo. We did not identify a significant effect on urine residual volume, with an estimated ratio of geometric means of 0.9 (0.3, 2.6), p = 0.84. There were no significant differences in ORSDS or QoR. There were 19 (29%) patients assigned to naloxegol who needed indwelling urination catheterization versus 7 (11%) patients in the placebo group, p = 0.012. Conclusions: Our results do not support use of naloxegol for postoperative urinary retention after hip and knee surgery.

Abstract licence: CC BY 4.0