Subcutaneous methylnaltrexone rapidly induced laxation in patients with advanced illness and opioid-induced constipation. Treatment did not appear to affect central analgesia or precipitate opioid withdrawal. (Clinical Trials.gov number, NCT00402038 [ClinicalTrials.gov].).

No abstract

Opioid analgesics are a cornerstone of pain therapy in the hospice and palliative care population. However, opioid-induced bowel dysfunction (OBD) is a commonly associated condition that frequently compromises the usefulness of these agents. Although its most common and debilitating symptom is constipation, the impact of OBD extends beyond constipation to encompass a myriad of gastrointestinal (GI) signs and symptoms, ranging from decreased gastric emptying and reflux to abdominal pain, cramping, bloating, nausea, and vomiting. Even after aggressive therapies to improve bowel function have been implemented, many patients continue to experience symptoms of OBD. To avoid these unwanted effects, some even choose to decrease or discontinue therapy with opioid analgesics, and experience inadequate pain control. The net result of OBD is a seriously negative impact on quality of life (QOL). For these reasons, it is important that palliative care practitioners have an adequate understanding of normal GI function and the underlying mechanisms responsible for OBD, the burden of OBD in the context of appropriate and effective pain management, and the benefits provided by effective pharmacotherapy. Several real-world cases are discussed to illustrate the application of optimal symptom management and the use of strategies that minimize the effects of OBD and improve patient QOL.

Methylnaltrexone is a methylated form of the mu-opioid antagonist naltrexone that blocks peripheral effects of opioids without affecting centrally mediated analgesia. The authors conducted a 3-month open-label extension trial of methylnaltrexone in patients with advanced illness and opioid-induced constipation (OIC). Following completion of a 2-week double-blind (DB) trial, 82 patients with OIC who did not respond to laxatives received subcutaneous (SC) methylnaltrexone as needed for up to 3 months. Patients received 0.15 mg/kg as a first dose, adjusted to 0.3 mg/kg or 0.075 mg/kg as needed (maximum of one dose per 24 hours). Mean laxation response (rescue-free bowel movement within 4 hours) rates (DB phase, months 1, 2, 3 open-label phase) were 45.3%, 45.5%, 57.7%, and 57.3%, respectively, for patients treated with DB methylnaltrexone and 10.8%, 48.3%, 47.6%, and 52.1%, respectively, for patients treated with DB placebo. Median time to laxation among responders was 45 minutes (range 0-4 hours) for all doses. Approximately 50% of patients reported improvement in constipation distress. Patient and investigator global clinical impression of change scores also improved. There were minimal changes in pain scores and opioid withdrawal symptoms. Adverse events included abdominal pain and nausea, mostly mild or moderate in severity. SC methylnaltrexone administered PRN (as needed) for up to 3 months continued to rapidly induce laxation in advanced illness patients with OIC.