Extended-release morphine sulfate and naltrexone hydrochloride (EMBEDA®): naltrexone-associated withdrawal and abuse-related effects in patients with chronic pain and recreational opioid users

AbstractObjective: To review the effects of naltrexone on withdrawal-related adverse events (AEs) and euphoria-related effects, and relationship between plasma naltrexone concentrations and withdrawal across EMBEDA® (MSN; extended-release morphine sulfate with sequestered naltrexone) studies.Methods: Five studies in pain patients and a safety review summarizing AE reports during the first year following approval of MSN were assessed for withdrawal reports. Three of these studies also assessed Clinical Opiate Withdrawal Scale (COWS) scores. Plasma naltrexone concentrations of MSN-treated individuals were summarized. Abuse potential was assessed in four studies in non-dependent recreational opioid users.Results: Withdrawal AEs occurred in 13/1781 patients across five MSN studies, and 25/182 cases involving withdrawal were reported in the safety review. In three of these studies, 11/964 patients experienced moderate withdrawal (COWS score = 13–24) and 1/964 patients experienced moderately severe withdrawal (...