Schifano Fabrizio, Chiappini Stefania, Corkery John Martin, Guirguis Amira
Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom.
Front Pharmacol. 2019 Feb 1;10:46. doi: 10.3389/fphar.2019.00046. eCollection 2019.
A recent, global, increase in the use of opioids including the prescribing, highly potent, fentanyl has been recorded. Due its current popularity and the potential lethal consequences of its intake, we aimed here at analyzing the fentanyl misuse, abuse, dependence and withdrawal-related adverse drug reactions (ADRs) identified within the European Medicines Agency (EMA), the United Kingdom Yellow Card Scheme (YCS), and the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) databases. Descriptive analysis of both ADRs and related cases. The analysis of fentanyl-related misuse, abuse, dependence and withdrawal cases reported during years 2004-2018 to the EMA, the YCS, and the FAERS showed increasing levels overtime, specifically, EMA-related data presented two peaks (e.g., in 2008 and 2015), whilst the FAERS dataset was characterized by a dramatic increase of the ADRs collected over the last 18 months, and particularly from 2016. Some 127,313 ADRs (referring to = 6,161 patients/single cases) related to fentanyl's misuse/abuse/dependence/withdrawal issues were reported to EMA, with 14,287 being judged by the reporter as "suspect." The most represented ADRs were: "drug dependence "(76.87%), "intentional product misuse" (13.06%), and "drug abuse" (7.45%). Most cases involved adult males and the concomitant use of other prescribing/illicit drugs. A range of idiosyncratic (i.e., ingestion/injection of transdermal patches' fentanyl) and very high-dosage intake cases were here identified. Significant numbers of cases required either a prolonged hospitalization (192/559 = 34.35%) or resulted in death (185/559 = 33.09%). Within the same time frame, YCS collected some 3,566 misuse/abuse/dependence/withdrawal ADRs, corresponding to 1,165 single patients/cases, with those most frequently reported being "withdrawal," "intentional product misuse," and "overdose" ADRs. Finally, FAERS identified a total of 19,145 misuse/abuse/dependence/withdrawal-related cases, being "overdose," withdrawal, and "drug use disorder/drug abuse/drug diversion" the most represented ADRs (respectively, 43.11, 20.80, and 20.29%). Fentanyl abuse may be considered a public health issue with significant implications for clinical practice. Spontaneous pharmacovigilance reporting systems should be considered for mapping new trends of drug abuse.
据记录，近期全球阿片类药物的使用有所增加，包括开具强效芬太尼的处方。鉴于其当前的流行程度及其摄入可能导致的致命后果，我们旨在分析欧洲药品管理局（EMA）、英国黄卡计划（YCS）和美国食品药品监督管理局（FDA）不良事件报告系统（FAERS）数据库中所识别出的与芬太尼滥用、误用、依赖及戒断相关的药物不良反应（ADR）。对ADR及相关病例进行描述性分析。对2004年至2018年期间向EMA、YCS和FAERS报告的与芬太尼相关的滥用、误用、依赖及戒断病例的分析显示，其数量随时间推移不断增加。具体而言，EMA相关数据出现了两个峰值（如2008年和2015年），而FAERS数据集的特点是在过去18个月，尤其是从2016年开始，所收集的ADR数量急剧增加。向EMA报告的与芬太尼滥用/误用/依赖/戒断问题相关的约127,313例ADR（涉及6,161名患者/单一病例）中，报告者将14,287例判定为“可疑”。最常见的ADR为：“药物依赖”（76.87%）、“故意药物误用”（13.06%）和“药物滥用”（7.45%）。大多数病例涉及成年男性以及同时使用其他处方/非法药物。在此识别出一系列特异质性病例（即摄入/注射透皮贴剂中的芬太尼）和高剂量摄入病例。大量病例需要延长住院时间（192/559 = 34.35%）或导致死亡（185/559 = 33.09%）。在同一时间范围内，YCS收集了约3,566例滥用/误用/依赖/戒断ADR，对应1,165名单一患者/病例，最常报告的是“戒断”、“故意药物误用”和“过量用药”ADR。最后，FAERS共识别出19,145例与滥用/误用/依赖/戒断相关的病例，最常见的ADR为“过量用药”、“戒断”以及“药物使用障碍/药物滥用/药物转移”（分别为43.11%、20.80%和20.29%）。芬太尼滥用可被视为一个对临床实践有重大影响的公共卫生问题。应考虑利用自发的药物警戒报告系统来梳理药物滥用的新趋势。
