Clinical toxicity of nitazene detections in two Australian emergency department toxicosurveillance systems
Open accessAbstract
Introduction: Nitazenes are a group of potent synthetic opioids that have had increasing prominence as novel psychoactive drugs in the last 5 years. We describe emergency department nitazene‐related presentations. Methods: This is a prospective series of patients with analytically confirmed nitazene presentations identified by the Emerging Drugs Network of Australia and Emerging Drugs Network of Australia Victoria. Both studies' databases were searched between July 2020 and February 2024 with clinical data and blood nitazene concentrations abstracted. Results: There were 32 presentations, 23 (72%) males, with a median age of 31 years (range 18–63 years). Only five (16%) intentionally ingested a nitazene, with most (12, 38%) believing they had taken alternative opioids. Co‐exposures occurred in 31 (97%), mostly metamfetamine. Naloxone was administered in 23 (72%) presentations, with a median total dose of intravenous naloxone within 1 h post hospital presentation of 400 μg (interquartile range [IQR] 160–450 μg). Four (13%) received a naloxone infusion. Thirteen (41%) were admitted to the intensive care unit. The median length of stay was 17 h (IQR 7–39 h). Protonitazene was the commonest nitazene detected in 23 (72%) presentations with a median concentration of 2.0 μg/L (range 0.7–15 μg/L). The lowest concentration of protonitazene in a patient that received naloxone was 0.7 μg/L. Discussion and Conclusions: Most patients were unaware they were using nitazenes. Given their potency, this has important implications for harm, particularly in those not intentionally using opioids. Nitazene exposure was mostly unintentional. Naloxone use was common and standard dosing regimens appeared effective in most cases.
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Following international scheduling in 2021, a rapid proliferation of other nitazene analogues has emerged worldwide, with dozens reported in toxicology investigations and seized-drug casework.
“Following its international scheduling in 2021, a rapid proliferation of other nitazene analogues has emerged worldwide, with dozens of different nitazene analogues now reported in both toxicology investigations and seized-drug casework [6,7,8,9].”
From Nitazenes: The Emergence of a Potent Synthetic Opioid Threat (2025) · cites this paper as [6]
The Introduction (page unavailable) says that multiple nitazene analogues emerged after isotonitazene was scheduled. It does not give a 2021 date, establish that the proliferation was rapid, or say that dozens of analogues were reported in both toxicology investigations and seized-drug casework. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe first nitazene widely identified in the recreational drug market was isotonitazene, in 2019, in Europe, Canada, and the United States.
“The first nitazene to be widely identified in the recreational drug market was isotonitazene, in 2019, in Europe, Canada, and the United States.”
From Nitazenes: The Emergence of a Potent Synthetic Opioid Threat (2025) · cites this paper as [6]
The Introduction (page unavailable) says nitazenes emerged as street drugs in 2019 and that isotonitazene initially dominated. It mentions later nitazene-related fatalities across North America and Europe, but does not establish that isotonitazene was widely identified in Europe, Canada, and the United States in 2019. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe rapid metabolism of nitazenes and the involvement of polymorphic CYP enzymes may influence individual susceptibility to intoxication and addiction, while also complicating toxicological and forensic analysis.
“Furthermore, the rapid metabolism of nitazenes and the involvement of polymorphic CYP enzymes may influence individual susceptibility to intoxication and addiction, while also complicating toxicological and forensic analysis [6,12,35,42].”
From Nitazenes: The Emergence of a Potent Synthetic Opioid Threat (2025) · cites this paper as [6]
The Discussion (page unavailable) says nitazene pharmacokinetics and those of active metabolites are not well described; it cites a short half-life in a rat model but does not establish rapid metabolism. Searches for polymorphic CYP enzymes, individual susceptibility, addiction, and complications for toxicological or forensic analysis found no passage addressing those claims. (LLM, conf=0.77)
Experimental — accuracy not yet measured
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“Furthermore, the rapid metabolism of nitazenes and the involvement of polymorphic CYP enzymes may influence individual susceptibility to intoxication and addiction, while also complicating toxicological and forensic analysis [6,12,35,42].”
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- Authors
- Isoardi, K. Z., Alfred, S., Weber, C., Harris, K., Soderstrom, J., Syrjanen, R., Thompson, A., Schumann, J., Stockham, P., Sakrajda, P., Fatovich, D., Greene, S. L., & the EDNA and EDNAV Investigators
- Affiliations
- The University of Queensland (AU)
- Royal Adelaide Hospital (AU)
- The University of Western Australia (AU)
- Austin Hospital (AU)
- Queensland Health (AU)
- Victorian Institute of Forensic Medicine (AU)
- Toxicology, Forensic Science Adelaide Australia
- ChemCentre (AU)
- The University of Melbourne (AU)
- Corresponding author
- Isoardi, Katherine Z.
- ORCID
- Venue
- Drug and Alcohol Review
- Publisher
- Wiley
- Published
- 2025-01-19
- Volume
- 45
- Issue
- 1
- Pages
- e13998-e13998
- ISSN
- 0959-5236 (ISSN-L)
- 1465-3362
- OpenAlex
- W4406628356
- Cited by
- 26
- References
- 22
- Citations by year
- 2026: 12 · 2025: 14
- FWCI
- 13.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Drug and Alcohol Review (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion, other-oa)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- National Health and Medical Research Council (GNT2001107)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
- Health Sciences › Medicine › Emergency Medicine › Poisoning and overdose treatments
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Keywords
- nitazenes, synthetic opioids, new psychoactive substances, emergency department presentation, clinical toxicity, naloxone, naloxone dosing, intensive care unit admission
- MeSH terms
- Adolescent, Adult, Analgesics, Opioid, Australia, Emergency Service, Hospital, Female, Humans, Male, Methane, Middle Aged, Naloxone, Narcotic Antagonists, Nitroparaffins, Prospective Studies, Victoria, Young Adult
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