Background: Several data sources are used to detect pharmacovigilance signals, and methods to generate safety signals and assess additional Risk Minimization Measures (aRMMs) post-marketing are needed. Here we improvise using Medication Utilization Evaluation (MUE) as a data source for effective pharmacovigilance and to capture safety information from real-world data using EHRs, in collaboration with multiple hospitals. Several studies highlighted challenges in adherence to the aRMMs.
Objectives: We aimed to assess the adherence to aRMMs and collect safety information for Fingolimod, Clozapine, Perfenidone, and Bosentan in Saudi Arabia using MUEs in collaboration with several hospitals.
Methods:
Design: A cross-sectional study. Setting: 19 hospitals were invited across the Kingdom (Northern, Southern, Eastern & Western regions) to participate in the study. Exposures or interventions: Ten tertiary hospitals that had ≥1 of the aforementioned medications agreed to participate. The index date was the first recorded prescription of Bosentan, Clozapine Fingolimod, or Pirfenidone between February 2021 and December 2022. Main outcome measures: The primary outcome was the proportion of patients who received laboratory screening according to SFDA-approved aRMMs (liver profile for Bosentan, Fingolimod, and Pirfenidone or blood count for Clozapine). Other data included demographics, prescription patterns, and reported Adverse Drug Reactions (ADRs). Statistical analysis: Statistical Analysis was performed using Jamovi software version 1.2.2.0.
Results: A total of 411 patients were included. Fingolimod (N= 237, 57.6%), Perfenidone (N= 46,11.19 %) and Bosentan (N= 85, 20.6%) aRMMs were assessed for potential hepatic impairment. While Clozapine (N= 43, 10.40%) aRMMs were assessed for potential agranulocytosis. The overall adherence to aRMMs for Fingolimod, Clozapine, Pirfenidone, and Bosentan was 7.3%,12.2 %, 36.4% and 29%, respectively. Drug-induced liver injury was observed with Fingolimod, Perfenidone, and Bosentan use in 9, 3, and 4 patients, respectively. Liver failure (N=11) and drug interaction (N=7) were observed with Fingolimod use.
Conclusions: The study showed poor adherence to aRMMs among healthcare providers for Fingolimod, Clozapine, Bosentan, and Pirfenidone. Cases of liver injury were detected. This indicated the benefits of using MUE as a post-marketing tool for medication safety profile and aRMMs adherence assessment. SFDA will cooperate with their stakeholders to improve the implementation of aRMMs of these products and perform necessary regulatory actions.
