Abstract
Opioid-induced constipation (OIC) has become increasingly prevalent with the rise of prescription opioid use and can significantly impact quality of life, especially in patients with advanced illness. Methylnaltrexone has proven effective in treating cancer patients with OIC who have not responded adequately to conventional laxative therapy, though use is relatively contraindicated in those with peritoneal carcinomatosis due to theoretical risk and reported cases of perforation. The aim of this study was to evaluate the safety of methylnaltrexone in patients with carcinomatosis. We performed a retrospective review of 3058 pediatric and adult patients who received methylnaltrexone at Memorial Sloan Kettering Cancer Center from 2009–2016. Data collected included age, cancer diagnosis, history of abdominal surgery, prior radiation therapy, evidence of peritoneal carcinomatosis, and complications. Charts were reviewed for any complications at 24 hours, 72 hours, and one week following drug administration, as well as at present. We identified 3058 patients (median age 56, range 1–95) who received a total of 3995 doses of methylnaltrexone. Three hundred thirty three (median age 55, range 4–88) had peritoneal carcinomatosis. The most common primary malignancies included pancreatic (17.7%), ovarian (13.5%), colon (7.2%), and lung (6.6%). 228/333 (68.4%) had a history of abdominal surgery and 85/333 (25.5%) underwent prior radiation therapy. Three patients had adverse outcomes or complications, with only one (0.3%) thought to be related to methylnaltrexone use. To our knowledge, this is the largest study to evaluate the outcomes of patients with carcinomatosis receiving methylnaltrexone and the first to include pediatric patients. We found one perforation attributed to methylnaltrexone. Methylnaltrexone should be considered for treatment of refractory OIC in cancer patients with peritoneal carcinomatosis due to low risk of complications.
Highlights
Opioid-induced constipation (OIC) has become increasingly prevalent with the rise of prescription opioid use
The study was approved by the Memorial Sloan Kettering Cancer Center Institutional Review Board (IRB) prior to initiation of chart review
We identified 3058 patients who received a total of 3995 doses of methylnaltrexone
Summary
Opioid-induced constipation (OIC) has become increasingly prevalent with the rise of prescription opioid use. In contrast to other opioid side effects like nausea and sedation, tolerance does not develop to bowel dysfunction and constipation[3]. Severe OIC may limit opioid therapy, decreasing analgesia, and substantially compromising quality of life, especially in patients with advanced cancer. Methylnaltrexone bromide (Relistor, Salix Pharmaceuticals), an opioid antagonist approved by the U.S Food and Drug Administration in 2008, has proven effective in treating cancer patients with OIC who are receiving palliative care and have not responded to conventional laxative therapy. The drug acts as a peripherally-acting mu-opioid receptor antagonist in the gastrointestinal (GI) tract, decreasing the constipating effects of opioids without impacting opioid-mediated analgesic effects on the central nervous system (CNS). GI perforation was reported in adult patients with OIC and advanced illness with conditions associated with localized or diffuse reduction of structural integrity in the wall of the GI tract. The aim of this study was to evaluate the safety of methylnaltrexone in patients with carcinomatosis
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