Overdose Deaths Related to Fentanyl and Its Analogs

Discussion

Evidence from the toxicologic analyses of unintentional overdose deaths in Ohio from the beginning of 2017 indicate the increasing and substantial role of IMFs, and the declining presence of heroin and pharmaceutical opioids in overdose fatalities, compared with 2014–2016 data from Ohio and other states.^[3–5] Approximately 90% of unintentional overdose deaths in 24 Ohio counties that occurred during January and February 2017 involved fentanyl, fentanyl analogs, or both. Approximately 32% of fentanyl-positive decedents did not test positive for norfentanyl, a major metabolite for fentanyl, suggesting a very rapid death.^[6] Twenty-one decedents tested positive for carfentanil, a highly toxic IMF compound (approximately 10,000 times more potent than morphine), which is frequently used in veterinary medicine for sedation of large animals. Approximately one third of unintentional overdose deaths that tested positive for IMF also tested positive for cocaine. It is not known whether these data indicate a pattern of intended polydrug use or if cocaine and IMF mixtures were sold to unsuspecting illicit opioid or cocaine users.

The study documents the high numbers of acryl fentanyl– and furanyl fentanyl–associated deaths among unintentional overdose fatalities in the United States. Acryl fentanyl is more potent than fentanyl;^[7] in 2016, there were reports of furanyl fentanyl–related overdoses in Canada caused by smoking contaminated cocaine.^[8] These drugs are commonly advertised on cryptomarkets, which are commercial web-based marketplaces for transactions involving drugs and other illicit goods that provide anonymity to both buyers and sellers via their location on the "Dark" web (internet content that requires specific software or authorization to access) and use of cryptocurrencies (e.g., bitcoin) for payment. Nearly half of fentanyl positive cases and approximately 90% of furanyl fentanyl positives tested positive for 4-ANPP. 4-ANPP is used as a precursor for the manufacture of fentanyl-type drugs; it is also an impurity found in fentanyl preparations and is a metabolite of fentanyl and furanyl fentanyl.^[9]

The findings in this report are subject to at least four limitations. First, for counties other than Montgomery, unintentional overdose numbers represent cases sent to MCCO for an autopsy and might not reflect all overdose deaths in that county. Further, it is not known whether there are systemic differences across counties (other than Montgomery County) regarding the types of cases sent to MCCO for testing. Second, toxicology reports cannot distinguish between pharmaceutical and illicitly manufactured fentanyl, although previous reports indicate that the majority of fentanyl linked to fatal unintentional overdoses in the country is suspected to be IMF.^[10] Third, toxicology data on decedents testing positive for multiple drugs cannot determine if the decedent knowingly or unknowingly used combinations of different drugs. Finally, data were obtained from 24 Ohio counties, and findings might not be generalizable to the entire state.

Overall, IMFs are appearing in combination with other fentanyl analogs, and co-occurrence of other drugs is common. The high percentage of overdose fatalities testing positive for combinations of IMFs might indicate that available street drugs include mixtures of different types of IMFs or that persons use drugs obtained from multiple sources, with different toxicologic profiles. Expansion of access to evidence-based treatment is an important strategy for preventing fentanyl-related overdoses.^[3] These findings highlight the urgent need to make IMF testing a part of standard toxicology panels for biological specimens used by substance abuse treatment centers, criminal justice institutions, and medical providers. Implementation of harm reduction initiatives could also help reduce the adverse consequences of IMF use.^[3,5] Because multiple naloxone doses are often required to reverse overdoses from IMFs,^[5] assuring that sufficient supplies are provided to first responders and distributed through community overdose prevention programs can mitigate the effects of opioid overdoses.

Morbidity and Mortality Weekly Report. 2017;66(34):904-908. © 2017  Centers for Disease Control and Prevention (CDC)