Subcutaneous Methylnaltrexone for Opioid-Induced Constipation in Advanced-Illness Patients With or Without Active Cancer

Abstract

Aim: To evaluate methylnaltrexone for opioid-induced constipation in patients with and without cancer. Methods: This post hoc analysis comprises two Phase III, multicenter, double-blind, randomized studies of advanced-illness patients who received methylnaltrexone subcutaneous injection or placebo. Results: Significantly more patients treated with methylnaltrexone than placebo experienced laxation within 4 (cancer = 55.5 vs 15.5%; noncancer = 55.6 vs 12.8%) and 24 (cancer = 64.7 vs 29.8%; noncancer = 64.4 vs 30.8%) h after the first dose (p < 0.01 vs placebo). Regardless of cancer status, methylnaltrexone reduced median time to laxation and improved constipation relief without impacting opioid analgesia or withdrawal symptoms. Conclusion: Methylnaltrexone provided significant improvements in opioid-induced constipation over placebo in advanced-illness patients with and without cancer. Clinical trial registration numbers: study 301: NCT00401362; study 302: NCT00402038.

Management of Opioid-Induced Constipation and Bowel Dysfunction: Expert Opinion of an Italian Multidisciplinary Panel

“…Several randomised, double-blind, placebocontrolled trials have investigated the efficacy and safety of methylnaltrexone both in patients with cancer-related [140][141][142][143] and non-cancerrelated [144][145][146][147] pain. In addition, meta-analyses have shown that methylnaltrexone improves bowel function (both subjectively and objectively), is well tolerated and reduces healthcare resource utilisation, but does not compromise the analgesic efficacy of concomitantly administered opioids [148,149].…”

Laxatives and Erectile Dysfunction Medications to Treat Side Effects of Opioid Agonist and Methadone Maintenance Therapy

“…15 Common treatments for constipation include dietary and lifestyle interventions (such as increased fibre and/or exercise) and/or laxatives (including stimulants, stool softeners, and fibre supplements). 16 Although there is some information and evidence to inform the treatment of opioid-induced constipation in patients receiving prescribed opioids, [17][18][19] less information is known to be available to inform best practices for treating OUD patients with constipation as a side effect of OAT or MMT.…”

“…22 Most of the evidence in this topic area was found to address either the clinical effectiveness of OAT and/or MMT 28,29 or the side effects from prescribed opioid medications in patients living with pain. [17][18][19]30,31 Although existing guidelines offer recommendations about the use of OAT and/or MMT to treat OUD, there were no guidelines identified informing the management or treatment of constipation or ED as side effects of OAT and/or MMT. 1,8 CADTH has previously assembled a body of evidence relevant to opioids, 32,33 including reports that have assessed and summarized evidence specific to the use of OAT and MMT and its effects on people living with OUD.…”

“…Several sources were identified in this review that described investigations into the treatment of constipation as a side effect of opioid medication prescribed for patients with chronic pain [17][18][19]30 ; however, there were no studies that described the treatment of constipation as a side effect of OAT or MMT. Notably, the sources identified did not describe investigation into the use of laxatives to treat opioid-induced constipation; rather, these studies assessed the use of naldemedine 17,30 and methylnaltrexone.…”

“…Notably, the sources identified did not describe investigation into the use of laxatives to treat opioid-induced constipation; rather, these studies assessed the use of naldemedine 17,30 and methylnaltrexone. 18,19 Several studies that assessed sexual dysfunction and/or ED were identified but did not meet the eligibility criteria for this review -many were observational and, as such, did not assess an intervention. 12,24,25,40 Two such studies assessed measures of sexual dysfunction and/ or ED and other psychological parameters in men living with OUD and receiving MMT as compared to men not receiving MMT.…”