Clinical Experiences With the Nitazene Class of Synthetic Opioids: A Cohort Study

STUDY OBJECTIVES: Nitazenes are illicit novel opioid agonists, and data describing the clinical course, management, and outcome of nitazene opioid poisoning are limited. The aim of this study is to describe our clinical experiences with analytically confirmed nitazene opioid exposures. METHODS: We extracted data on analytically confirmed nitazene opioid exposures in a cohort of prospectively identified cases in a state-based comprehensive surveillance program in New South Wales, Australia. RESULTS: We identified 27 laboratory-confirmed nitazene opioid exposures from June 2018 to March 2025. We observed 20 unintentional acute opioid poisonings and 7 acute withdrawals in predominantly younger men. Protonitazene, protonitazepyne (N-pyrrolidino-protonitazene), and isotonitazene were the most detected nitazene opioid compounds. The most common route of exposure was vaping; other exposures included injection, ingestion, and nasal insufflation. Nitazene opioids were sought in 8/21 (38%) of cases where intent was known. Acute poisoning typically presented with sedation and hypoventilation, necessitating endotracheal intubation in severe cases due to cardiac arrest and/or hypoxemia. Naloxone was effective, with a median parenteral reversal dose of 400 μg (interquartile range 400 to 800 μg) and repeat dosing was given in 45% of the 11/16 cases receiving naloxone. CONCLUSION: This case series highlights that standard parenteral naloxone doses are typically effective, but ongoing monitoring is necessary to detect renarcotization. Nitazene opioids display novel consumption patterns, including exposure by vaping and unintentional use in products sold as containing another drug. The risk of opioid withdrawal from regular nitazene opioid use is a novel observation. Monitoring trends through active drug surveillance, public education, and community access to naloxone are crucial to mitigate the harm posed by nitazene opioid opioids.