Rising Numbers of Deaths Involving Fentanyl and Fentanyl Analogs, Including Carfentanil, and Increased Usage and Mixing with Non-opioids July 13, 2018 Public Health 829 Summary This is an alert to public health departments, health care professionals, first responders, and medical examiners and coroners to important new developments in the evolving opioid overdose epidemic, which increasingly involves illicitly manufactured fentanyl and an array of potent fentanyl analogs (i.e., compounds that are chemically related to fentanyl). It is the second update to the original health advisory, HAN 384, issued October 26, 2015, which alerted the public to the increase in unintentional overdose fatalities involving fentanyl in multiple states, primarily driven by illicitly manufactured fentanyl. The first update to this health advisory was released on August 25, 2016 (HAN 395), describing the sharp increase in the availability of counterfeit pills containing varying amounts of fentanyl and fentanyl analogs, the continued increase of overdose deaths involving fentanyl across a growing number of states, and the widening array of fentanyl analogs being mixed with heroin or sold as heroin. The current update includes information on: (1) the continued increase in the supply of fentanyl and fentanyl analogs detected by law enforcement; (2) the sharp rise in overdose deaths involving fentanyl and fentanyl analogs in a growing number of states, in particular the growing number of deaths involving the ultra-high potency fentanyl analog known as carfentanil; (3) the expanding number of poly-drug combinations implicated in opioid overdose deaths, which include non-opioids, such as cocaine; (4) the updated comprehensive guidance available to law enforcement and other emergency responders to prevent occupational exposure to fentanyl and fentanyl analogs; and (5) updated recommendations for public health professionals and health care providers regarding prevention and response efforts. Background The supply, distribution, and potency of illicitly manufactured fentanyl and fentanyl analogs in the U.S. drug market is continuously evolving. The Drug Enforcement Administration's (DEA) National Forensic Laboratory Information System (NFLIS), which systematically collects drug identification results from drug cases submitted for analysis to forensic laboratories (referred to as drug submissions), estimated that drug submissions testing positive for fentanyl more than doubled from 2015 to 2016, rising from 14,440 to 34,119. This increase continued into 2017, with an estimated 25,460 reports in the first six months of 2017 alone [1,2,3]. In 2016, states reporting the highest number of fentanyl drug submissions remained concentrated in the East and Midwest, with all being located east of the Mississippi River, or bordering the Mississippi River. This geographic clustering of states is believed to be related to the supply chains of the white powder heroin market, which predominates east of the Mississippi [10]. Illicitly manufactured fentanyl powder can be readily mixed with white powder heroin or mimic this form of heroin, while black tar heroin, which is primarily sold west of the Mississippi, is more difficult to blend with fentanyl powder. During January–June, 2017, NFLIS received an increased number of reports from state and local forensic laboratories of fentanyl analogs and other synthetic illicit opioids (e.g., U-47700, described below) detected among drug submissions. This included two extremely potent fentanyl analogs, carfentanil and 3-methylfentanyl, which are 100 and 4 times more potent than fentanyl, respectively [4]. Carfentanil drug submissions reported to NFLIS rapidly increased from an estimated 1,251 in 2016 to 2,268 during the first six months of 2017 (see table below) [2, 3]. In 2016, a total of 11 states reported carfentanil drug submissions, including Ohio with more than 900 reports and Florida with more than 100 reports. The other 9 states each submitted between 1 and 49 carfentanil reports [3]. Further spread is expected as new states report overdose deaths related to carfentanil in 2017. Other fentanyl analogs rising in prominence during 2016-17 are 3-methylfentanyl, furanylfentanyl, and acrylfentanyl (see table below) [2, 3]. Finally, drug submissions testing positive for a synthetic illicit opioid known as U-47700, first encountered by the DEA in 2016, increased from 533 submissions in 2016 to 1,087 during January–June, 2017 [1,2]. This newly emerging illicit opioid was temporarily placed under Schedule I control under the Controlled Substances Act in October 2016, allowing for criminal prosecution of those who possess, import, distribute, or manufacture it. Read more to find recommendations from the CDC.