Adverse Events and Drug Interactions Associated with Elexacaftor/Tezacaftor/Ivacaftor Treatment: A Descriptive Study Across Australian, Canadian, and American Adverse Event Databases

Abstract

People with cystic fibrosis may experience polypharmacy, which can increase the risk of drug induced complications such as adverse events and drug-drug interactions. This study aimed to examine the prevalence of adverse events and to identify potential drug-drug interactions associated with elexacaftor/tezacaftor/ivacaftor (ETI). Three databases, the Australian Therapeutic Goods Administration Database of Adverse Event Notification (TGA DAEN), the Canada Vigilance Adverse Reaction Online Database (CVAROD), and the USA Food and Drug Administration Adverse Event Reporting System (FAERS) Database were searched for spontaneous ETI adverse events between 2019 and 2024. Descriptive analysis of the data was undertaken. The FAERS database was analysed to identify adverse events of interest such as anxiety and depression and concomitant drugs prescribed with ETI. A total of 10,628 ETI associated adverse events were identified in all system organ classes. The incidence of psychiatric adverse events ranged from 7 to 15% across the three databases. Potential drug-drug interactions with CYP 3A4/5 strong inhibitors and strong inducers were identified from the FAERS database and azole antifungals were implicated in several ETI dose modifications. The prevalence and types of ETI adverse events were varied and use of concomitant drugs with potential drug interactions was significant, requiring more research to manage them.

Keywords: adverse events; cystic fibrosis; drug–drug interactions; elexacaftor/tezacaftor/ivacaftor.