piperidines and naloxegol

To summarize and evaluate the existing literature regarding medications to treat opioid-induced constipation (OIC) in patients with chronic noncancer pain (CNCP).. PubMed, EMBASE, and Web of Science were searched using the following terms: constipation, opioid, chronic, pain, noncancer, nonmalignant, methylnaltrexone, alvimopan, lubiprostone, naloxegol, and naldemedine.. The search was limited to randomized controlled trials reporting human outcomes. Data extracted included the following: study design, population, intervention, control, outcomes related to OIC and safety, and potential biases assessed using Cochrane Collaboration's Risk of Bias Assessment Tool.. After assessment, 16 of the 190 studies were included: methylnaltrexone (n = 4), naloxegol (n = 3), naldemedine (n = 2), lubiprostone (n = 3), and alvimopan (n = 4). Lubiprostone was the only nonperipherally acting µ-opioid receptor antagonist included. Only 1 study (naloxegol) used "usual care" (nonstudy laxative) rather than placebo as a comparator. Placebo-controlled trials demonstrated benefit for methylnaltrexone, naloxegol, naldemedine, and lubiprostone, with conflicting evidence for alvimopan. No data suggest that one agent is better than another. Overall risk of bias across all studies was low to moderate.. With risk of bias determined to be low to moderate, published data to date suggest that methylnaltrexone, naloxegol, and naldemedine may be appropriate to treat OIC in patients with CNCP.

Topics: Analgesics, Opioid; Chronic Pain; Constipation; Evidence-Based Practice; Humans; Laxatives; Lubiprostone; Morphinans; Naltrexone; Narcotic Antagonists; Piperidines; Polyethylene Glycols; Quaternary Ammonium Compounds; Randomized Controlled Trials as Topic

Opioid-induced constipation (OIC) is a major side effect of opioid use. Centrally acting antagonists result in opioid withdrawal or worsening of pain and lead to use of peripherally acting mu-opioid receptor antagonists (PAMORAs). The required doses of the PAMORAs, methylnaltrexone and naloxegol, in the treatment of OIC are well established in chronic opioid users. OIC may occur after short duration of opioid treatment; the required doses of naloxone, naltrexone, and PAMORAs in opioid-naïve subjects (with no opioid use for at least 3 months) are unclear. The aim of this review was to evaluate the PAMORA dose required for opioid-naïve subjects to achieve similar beneficial effects on symptoms or valid surrogates to those observed in chronic opioid users.. A PubMed search of μ-opioid antagonists to counter μ-opioid effects included terms: naloxone, naltrexone, methylnaltrexone, alvimopan, and naloxegol, as well as OIC and colonic transit.. The approved dose of methylnaltrexone in chronic opioid users, 0.3 mg/kg subcutaneous (SQ), did not affect motility in opioid-naïve subjects. Trials investigating the required dose of alvimopan showed 0.5-1 mg dose was efficacious in treating OIC; a 10-fold higher dose (12 mg) of alvimopan is needed to block effects of codeine on small bowel and colonic transit in opioid-naïve subjects compared to chronic opioid users. Opioid-naïve users need 125 mg of naloxegol to reverse the effects of opioids on transit; this is in contrast to the 12.5 to 25 mg needed to treat OIC in chronic opioid users.. Opioid-naïve subjects require a higher dose of PAMORA than chronic opioid users to achieve μ-opioid antagonist effect.

Topics: Analgesics, Opioid; Constipation; Dose-Response Relationship, Drug; Gastrointestinal Agents; Humans; Morphinans; Narcotic Antagonists; Pain; Piperidines; Polyethylene Glycols; Receptors, Opioid, mu; Treatment Outcome

Topics: Analgesics, Opioid; Cancer Pain; Constipation; Enema; Gastrointestinal Agents; Gastrostomy; Humans; Laxatives; Morphinans; Naltrexone; Piperidines; Polyethylene Glycols; Practice Guidelines as Topic; Quaternary Ammonium Compounds

The use of alvimopan at the time of cystectomy has been associated with improved perioperative outcomes. Naloxegol is a less costly alternative that has been used in some centers. This study aims to compare the perioperative outcomes of patients undergoing cystectomy with urinary diversion who receive the mu-opioid antagonist alvimopan versus naloxegol.. This was a retrospective review that included all patients who underwent cystectomy with urinary diversion at our institution between 2007-2020. Comparisons were made between patients who received perioperative alvimopan, naloxegol and no mu-opioid antagonist (controls).. In 715 patients who underwent cystectomy, 335 received a perioperative mu-opioid antagonist, of whom 57 received naloxegol. Control patients, compared to naloxegol and alvimopan patients, experienced a significantly (p < 0.05) delayed return of bowel function (4.3 vs. 2.5 vs. 3.0 days) and longer hospital length of stay (7.9 vs. 7.5 vs. 6.5 days), respectively. The incidence of nasogastric tube use (14.2% vs. 12.5% vs. 6.5%) and postoperative ileus (21.6% vs. 21.1% vs. 13.3%) was also most common in the control group compared to the naloxegol and alvimopan cohorts, respectively. A multivariable analysis revealed that when comparing naloxegol and alvimopan, there was no difference in return of bowel function (OR 0.88, p = 0.17), incidence of postoperative ileus (OR 1.60, p = 0.44), or hospital readmission (OR 1.22, p = 0.63).. Naloxegol expedites the return of bowel function to the same degree as alvimopan in cystectomy patients. Given the lower cost of naloxegol, this agent may be a preferable alternative to alvimopan.

Topics: Cystectomy; Gastrointestinal Agents; Humans; Ileus; Length of Stay; Morphinans; Narcotic Antagonists; Piperidines; Polyethylene Glycols; Postoperative Complications; Urinary Diversion