The long-term safety of subcutaneous methylnaltrexone for the treatment of opioid-induced constipation in patients with chronic nonmalignant pain

Long-term use of opioid analgesics for the treatment of chronic pain may be complicated by dose-limiting side effects, most commonly opioid-induced constipation (OIC). Methylnaltrexone bromide, a selective peripherally acting mu-opioid receptor antagonist, decreases the peripheral side effects of opioids without affecting centrally mediated analgesia. The purpose of this open-label study was to determine the long-term safety and tolerability of subcutaneous (SC) methylnaltrexone in patients with chronic nonmalignant pain. This study included 1034 treated patients on stable doses of opioids who demonstrated constipation over the month prior to screening. After a 14-day screening period, eligible patients received methylnaltrexone bromide SC at least once weekly and up to once daily for 48 weeks. Use of routine laxatives was permitted for the duration of the study. 81.2% of patients reported at least one adverse event (AE) during the course of the trial. The most common treatment-emergent AEs (TEAEs), with an incidence of at least 5%, were abdominal pain (24.0%), diarrhea (16.4%), nausea (15.1%), hyperhidrosis (8.9%), vomiting (7.2%), abdominal pain upper (6.7%), back pain (6.4%), influenza (6.2%), upper respiratory infection (5.8%), headache (5.6%), flatulence (5.5%), sinusitis (5.3%), and dizziness (5.0%). Serious AEs were reported in 10.1% of patients. Discontinuation from active treatment because of AEs occurred in 157 (15.2%) patients. The most common AEs resulting in discontinuation from active treatment (>1.0%) were abdominal pain (4.7%), nausea (2.5%), diarrhea (2.3%), hyperhidrosis (1.5%), and vomiting (1.5%). The results of this study demonstrate that methylnaltrexone is generally well tolerated in patients with chronic nonmalignant pain and OIC, with an AE profile similar to what has previously been reported in patients with either chronic nonmalignant pain or advanced illness in studies of shorter duration.