Impact of Regulatory Interventions on Immediate Release Fentanyl and Alternatives Use in Spain: An Interrupted Time...

Immediate release fentanyl (IRF) is approved for breakthrough cancer pain. In February 2018, the Spanish Agency of Medicines and Medical Devices (AEMPS) issued a communication reminding the authorized conditions and risks. In July 2021, a prescription-controlled system was implemented to avoid use in non-cancer patients. We assessed the impact of these regulatory interventions on IRF use and alternatives such as immediate release morphine (IRM).

Ecological study using national data of defined daily dose (DDD) dispensed per 100 000 inhabitants and day (DID). Segmented regression analysis was conducted to quantify the impact of the regulatory interventions. Furthermore, inflection points identified through sensitivity analysis using joinpoint regression were incorporated to capture potential trend changes more accurately and enhance the robustness of the analysis.

The AEMPS communication was associated with an immediate decrease in IRF use (-1.57 DID), although it did not influence the trend, which had previously stabilized since 2017. The prescription-controlled system was associated with a substantial decline in level (-5.01 DID) and slope (-1.64 DID per quarter). IRM use increased continuously throughout the study period. After the last intervention, a rise was observed (0.27 DID), but no trend changes.

The prescription-controlled system was associated with a sharp decline in IRF use and a slight increase in IRM use, which can be attributed to restrictions applied to non-cancer patients. The increase in IRM use does not compensate for the decrease in IRF consumption, suggesting that other therapeutic strategies with opioids and non-opioid alternatives should be explored in these patients.