Abuse, dependence and withdrawal associated with fentanyl and the role of its (designated) route of administration: an analysis of spontaneous reports from Europe

Abstract

Purpose Fentanyl, a highly potent synthetic opioid used in cancer and non-cancer pain, is approved for various routes of administration. In Europe, fentanyl consumption increased substantially in the last decades but information on abuse, dependence and withdrawal associated with fentanyl is scarce, especially with respect to its different formulations. Methods We analysed case characteristics of spontaneous reports of suspected fentanyl-associated abuse, dependence or withdrawal from European countries recorded in the EudraVigilance database up to 2018 with respect to the (designated) routes of administration and potential indications. Results A total of 985 reports were included (mainly from France and Germany) with 43% of cases referring to transdermal fentanyl. Median age was 45 years (48.8% female) and 21.6% had musculoskeletal disorders. Only 12.6% of those using transdermal fentanyl had a cancer diagnosis compared to 40.2% and 26.8% of those using intranasal and oral transmucosal fentanyl, respectively. Depression was common (10.7%) and highest in cases with musculoskeletal disorders (24.9%) as was the use of benzodiazepines. Overall, 39.5% of reports resulted in a prolonged hospital stay and for 23.2% a fatal outcome was recorded. The respective proportions were especially high in cases with musculoskeletal disorders (56.3% with prolonged hospitalisation) and in those using transdermal fentanyl (35.2% fatalities). Conclusions In suspected cases of abuse, dependence or withdrawal, fentanyl was mainly used for non-cancer pain indications and most often as transdermal formulations. Depression and prolonged hospitalisations were common, especially in patients with musculoskeletal disorders, indicating a vulnerable patient group and complex treatment situations.

Fentanyl in cancer pain management: avoiding hasty judgments and discerning its potential benefits

“… 197 , 198 Furthermore, most cases of abuse, dependence or withdrawal in Europe are related to non-cancer pain indications and mostly to transdermal formulations. 196 Approximately 60% of patients using intranasal fentanyl and almost 75% of those using transmucosal fentanyl were not diagnosed with cancer, and more than 70% of both groups used no opioids for background pain. 196 …”

“… 196 Approximately 60% of patients using intranasal fentanyl and almost 75% of those using transmucosal fentanyl were not diagnosed with cancer, and more than 70% of both groups used no opioids for background pain. 196 …”

“…195 Fentanyl and its derivatives, either diverted from medical use or illicitly manufactured, play a comparatively small role in deaths and acute poisonings that occur in Europe. 196 The number of fentanyl-related fatal overdoses appears to be significantly lower in Europe than in the USA, with only 0.5% of people registering with drug treatment services citing fentanyl and its derivatives as their primary drug. 197,198 Furthermore, most cases of abuse, dependence or withdrawal in Europe are related to non-cancer pain indications and mostly to transdermal formulations.…”

“…197,198 Furthermore, most cases of abuse, dependence or withdrawal in Europe are related to non-cancer pain indications and mostly to transdermal formulations. 196 Approximately 60% of patients using intranasal fentanyl and almost 75% of those using transmucosal fentanyl were not diagnosed with cancer, and more than 70% of both groups used no opioids for background pain. 196 Collaborative efforts should still be intensified globally to find solutions that balance our responsibility to reduce deaths and overdoses with the ethical imperative to make opioids widely available to patients who need them to effectively manage chronic cancer pain without arbitrary restrictions on prescribing, dosing or access.…”

“…196 Approximately 60% of patients using intranasal fentanyl and almost 75% of those using transmucosal fentanyl were not diagnosed with cancer, and more than 70% of both groups used no opioids for background pain. 196 Collaborative efforts should still be intensified globally to find solutions that balance our responsibility to reduce deaths and overdoses with the ethical imperative to make opioids widely available to patients who need them to effectively manage chronic cancer pain without arbitrary restrictions on prescribing, dosing or access. Again, more nationwide educational programmes and training for clinicians involved in cancer pain management are needed to improve early diagnosis, appropriate treatment and adequate knowledge of the risks of overdose or misuse of analgesics.…”