(024) Impact of regulatory interventions on immediate release fentanyl and alternatives use in Spain: an interrupted time-series analysis

Background: Immediate release fentanyl (IRF) is only approved for patients with breakthrough cancer pain. In February 2018 the Spanish Agency of Medicines and Medical Devices (AEMPS) issued a communication reminding the IRF authorized conditions and risks of abuse and dependence. In July 2021 the Ministry of Health implemented a prescription controlled system to avoid the use in non-cancer patients.

Objectives: To assess the impact of these regulatory interventions on IRF use and alternatives such as immediate release morphine (IRM). Other previous co-interventions detected were also analyzed.

Methods: An interrupted time series analysis using aggregated data from the National Health System drug consumption database from 1st January 2012 to 31st December 2022. The number of Defined Daily Dose dispensed per 100,000 inhabitants and day (DID) was calculated per quarter.

Results: IRF use increased from 21.8 DID in the first quarter 2012 to 43.7 DID in the last quarter 2016 and remained stable until the second quarter 2021. A sharp decline was observed from this date until the end of the study period. The AEMPS communication was associated with a significant fall in level of -2.3 DID (95% CI: -2.89, -1.64), but not in slope. Nevertheless, previous co-interventions played a crucial role in significantly reducing and stabilizing the trend until the prescription controlled system was put in place displaying a significant drop in level and slope of -5.4 DID (95% CI: -6.32, -4.42) and -1.7 DID per quarter (95% CI: -1.91, -1.44), respectively. The interventions targeting IRF did not affect IRM use.

Conclusions: The prescription controlled system impacted significantly in the decline of IRF use, which might be attributed to the restrictions in non-cancer patients. The shift towards the use of other opioid and non-opioid alternatives should be further explored.