Acetyl Fentanyl, a Novel Fentanyl Analog, Causes 14 Overdose Deaths in Rhode Island, March–May 2013

From 2000 to 2011, the rate of death from unintentional drug poisoning in the USA more than doubled from 4.1 per 100,000 to 10.6 per 100,000, respectively [1]. Further, from 1999 to 2011, drug overdose deaths involving opioids quadrupled from 4030 to 16,917 [1]. Nationally, since 2009, more people have died each year from drug poisoning than from motor vehicle crashes [1]. In fact, overdose is the leading cause of adult unintentional injury death in Rhode Island, which is one of 30 states where overdose mortality exceeded motor vehicle collision mortality in 2010 [2]. The major driver of the increase in drug overdose deaths is pharmaceutical opioids. In 2010, 60 % of the unintentional drug poisoning deaths in the USA were caused by pharmaceuticals, and 75 % of the fatal pharmaceutical overdoses were caused by opioids [3]. Nationally, heroin use doubled from 2003 to 2012, and from 2002 to 2011, drug poisoning deaths involving heroin more than doubled from 2089 to 4397, respectively [4, 5]. In Rhode Island, overdose deaths caused by illicit drugs increased so much during 2011–2013 that it overtook fatal pharmaceutical overdoses, which remained steady during the same time period [6]. Fentanyl (N-(1-(2-phenethyl)-4-piperidinyl-N-phenyl-propanamide) is a synthetic opioid first synthesized by Janssen Pharmaceuticals in the 1960s and used medicinally since 1968. It is estimated to be between 80 and 100 times more potent than morphine [7, 8] and has over 200 chemical derivatives, some of which have been used recreationally or implicated in heroin adulteration in the past. The first fentanyl derivatives synthesized in the early 1970s showed similar pharmacokinetics but significantly different potencies. By the early 1980s, clandestinely produced synthetic fentanyl and fentanyl derivatives were becoming available on the black market [7, 9]. The speed of onset and potency of these drugs made them attractive to opioid users but also made them more dangerous. Fentanyl derivatives can be a few to hundreds of times more potent than heroin, and if users unknowingly obtain and administer packages sold as heroin but containing a more potent fentanyl derivative, this can lead to inadvertent overdose and death [10]. Several epidemics of overdose deaths caused by illicitly manufactured fentanyl- and fentanyl derivative-adulterated heroin have occurred in the USA since the 1970s, leaving more than 1000 dead in their wakes. The first epidemic was identified in California in 1978 and was associated with a compound later identified as the fentanyl analog 3-methylfentanyl, branded by the street name “China White.” This drug is several hundred times more potent than morphine and accounted for more than 100 deaths in California [7–9, 11]. This same drug resurfaced in 1988 in Pennsylvania, where it was implicated in the deaths of 16 persons [12, 13]. In 1991, covertly manufactured fentanyl was sold as heroin on the streets of New York City in small envelopes labeled “Tango and Cash.” Because of difficulties in cutting the drug, these samples contained highly variable amounts of fentanyl and their use resulted in 12 deaths [14]. More recently, from 2005 to 2007, an outbreak of fentanyl-contaminated heroin caused 1013 deaths across several states [15]. The Rhode Island State Health Laboratory preliminarily identified acetyl fentanyl, a fentanyl analog, as the cause of ten overdose deaths during March–April 2013. Acetyl fentanyl (N-phenyl-N-[1-(2-phenylethyl)-4-piperidinyl]-acetamide, monohydrochloride) is an illicit synthetic opioid that is four to five times more potent than heroin; it is not FDA approved, not prescribed by physicians, and not commercially available. The objectives of this investigation were to (1) determine if these drug overdose deaths represented an increase above baseline, (2) characterize the acetyl fentanyl overdose decedents, and (3) identify potential risk factors for acetyl fentanyl overdose death relative to those for other illicit drug overdose deaths.