PHARMACOVIGILANCE ANALYSIS OF INHALED FIXED-DOSE (ICS/LABA o ICS/LABA/LAMA) COMBINATIONS IN ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE

The present thesis analyses the evolution of the benefit/risk ratio of dual (ICS/LABA) and triple (ICS/LABA/LAMA) inhaled therapies in the treatment of asthma and Chronic Obstructive Pulmonary Disease (COPD). The two obstructive lung diseases are characterised by high global morbidity and mortality. In order to achieve this objective, chapters have been developed to serve the experimental analysis. These include in-depth studies on pharmacovigilance and its main operational tools, as well as the framing of the diseases and their pharmacological treatment plans. Finally, leveraging the insights gleaned from this study, it was feasible to delineate the safety profiles of the reference combinations. Specifically, the dual combination, including Beclometasone Dipropionate (BDP) and Formoterol Fumarate (FF), and the triple combination, consisting of Beclometasone Dipropionate (BDP), Formoterol Fumarate (FF), and Glycopyrrolate Bromide (GB), were characterised in depth. The investigation concentrated on the regulatory changes made to the printed materials (to the SmPC from Section 4.4 to 4.9) and aimed at monitoring, containment and risk management from the granting of the Marketing Authorisation (MA) to date. This was achieved by means of an examination of pharmacovigilance sources, including European Public Assessment Report (EPAR), Periodic Safety Update Report (PSUR), Risk Minimisation Measures (RMM), Risk Minimisation Plan (RMP), scientific literature, Package Leaflet (PL), Summary of Product Characteristics (SmPC) and internal data. Finally, a comparative analysis of the SmPCs of the combinations currently marketed for human use was carried out, highlighting the differences in safety-related content.