Evaluation of Opioid Overdose Reports in Patients Treated with Extended-Release Naltrexone: Postmarketing Data from 2006 to 2018

• Published in: Drug safety 2021-03, Vol.44 (3), p.351-359
• Main Authors: Jain, Priya, McKinnell, Kimberley, Marino, Rose, Vunnava, Prashanthi, Liles-Burden, Marie A., Desai, Avani, Wenten, Madé, Fratantonio, James, Akerman, Sarah C., Sullivan, Maria A., Bloomgren, Gary
• Format: Article
• Language: English
• Subjects: Adverse events; Dosage; Drug dosages; Drug overdose; Drug Safety and Pharmacovigilance; Drug tolerance; Latency; Medicine; Medicine & Public Health; Mortality; Naltrexone; Narcotics; Opioid receptors; Original; Original Research Article; Overdose; Patients; Pharmacology/Toxicology; Pretreatment; Safety; Sensitivity analysis
• ISSN: 0114-5916; 1179-1942
• DOI: 10.1007/s40264-020-01020-4

Introduction After treatment with naltrexone extended-release injectable suspension (XR-NTX), a µ-opioid receptor antagonist, opioid tolerance is reduced from pretreatment baseline. Patients may be vulnerable to opioid overdose if they attempt to override the blockade during treatment, at the end of a dosing interval, after missing a dose, or after discontinuing treatment. Objective We analyzed postmarketing data to characterize reporting rates of opioid overdose during treatment with and after discontinuation of XR-NTX. Methods Postmarketing adverse event reports within the XR-NTX safety database, received 2006–2018, for patients treated with XR-NTX for any indication were reviewed for opioid overdose cases. Assessable cases were categorized by timing of the event from the last dose of XR-NTX (latency): ≤28 days (on treatment), 29–56 days, and >56 days from last dose of XR-NTX. Within each latency group, cases were further classified as serious and, of those, cases that had a fatal outcome. Results During the 12-year period, an estimated 495,602 patients received XR-NTX. Opioid overdose was reported in 161 cases; of these, 66 contained sufficient information to determine latency. Reporting rates of opioid overdose per 10,000 patients treated were similar among latency groups: 0.54 for ≤28 days (0.24 fatal), 0.34 for 29–56 days (0.16 fatal), and 0.44 for >56 days (0.40 fatal) from the last dose of XR-NTX. Conclusions Over the 12-year period, the reporting rates of opioid overdose were similar during treatment with or after discontinuation of XR-NTX and