Assessing the 2004–2018 Fentanyl Misusing Issues Reported to an International Range of Adverse Reporting Systems

Abstract

Objective: 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.Methods: Descriptive analysis of both ADRs and related cases.Results: 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 n = 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%).Conclusion: 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.

Focus on Clozapine Withdrawal- and Misuse-Related Cases as Reported to the European Medicines Agency (EMA) Pharmacovigilance Database

“…Such listings showed all information related to the ADR, the patient, the drug, the reporter, and the diagnosis. In line with previous studies from our group [36][37][38][39], the ADRs considered here were, per se, voluntary and unsolicited communications [34] reported by both Regulatory Authorities of the EU Member States where the reaction occurred and/or by the Marketing Authorization Holders for those ADRs occurring outside the EEA. Individual Case Safety Reports, such as voluntary reports, refer to the format and content for the reporting of one or several suspected ADRs in relation to a medicinal product that occur in a single patient at a specific point of time [40].…”

“…Within the standardized MedDRA Query (SMQ) 'drug abuse, dependence and withdrawal' section, we identified the following ADRs: dependence, drug abuse, drug abuser, drug dependence, drug diversion, drug withdrawal convulsions, drug withdrawal syndrome, drug withdrawal neonatal syndrome, intentional product misuse, product use issue, substance abuse, and withdrawal syndrome. For the definition of 'abuse'; 'addiction'; 'dependence'; and 'misuse' please refer to references [35][36][37][38][39][40]. Moreover, in accordance with MedDRA, 'withdrawal' is identified in association with the abrupt cessation or reduction in intake of a drug in a habituated person.…”

Novel Opioids: Systematic Web Crawling Within the e-Psychonauts’ Scenario

“…For some opioids, larger dosages of naloxone may be required to reverse the opioid toxidrome than needed in case of a typical heroin overdose (Armenian et al, 2018;Lovrecic et al, 2019). The greatest levels of concerns remain related to fentanyl analogs, because of their harmful potential (Schifano et al, 2019a), the continuous high incidence of emerging analogs on the markets over the last years (Schueler, 2017), and the difficulties in identifying them with analytical chemistry techniques (Gerace et al, 2018b;Morrow et al, 2019). Conversely, those substances here identified possessing a full/partial kappa opioid receptor agonist activities (including salvinorin A and its derivatives; tifluadom; and pethidine) are likely to be particularly attractive for opioid and other research chemical consumers prone to a recreational experimentation associated with complex psychoactive effects (Coffeen and Pellicer, 2019).…”

Coming Off Prescribed Psychotropic Medications: Insights from Their Use as Recreational Drugs

“…A massive, recent, worldwide increase in opiate/opioid prescription levels has been identified, with fentanyl being a reason of particular concern [57][58][59]. Within the over-the-counter abuse ("pharming") opiate/opioid scenario, the anti-diarrhoeal loperamide has increasingly been reported by psychonauts as a recreational drug [60].…”