Findings on in vitro transporter-mediated drug interactions and their follow-up actions for labeling: analysis of drugs approved by US FDA between 2017 and 2021

Abstract

Understanding possible follow-up actions on in vitro findings helps determine the necessity of labeling for drug interactions. We analyzed information for in vitro findings on transporter-mediated interactions of drugs approved by the U.S. Food and Drug Administration's Center for Drug Evaluation and Research for the last five years (i.e., 2017-2021) and their follow-up actions for labeling. Higher R values than the pre-defined cut-off were observed with 3.7-39.1% inhibitor drugs in a simple prediction. Among these drugs, 16-41.7% were labeled with their potential drug interactions, while results of supporting studies or scientific rationales were submitted for the other drugs leading to no interaction labeling. In vitro transporter substrates were reported with 1.7-67.6% of drugs. The interaction labels for these substrate drugs were observed in up to 40% of drugs, while the other drugs were not labeled on the drug interactions with claims for their low interaction potential, evidenced by clinical studies or scientific rationales. The systematic and comprehensive analysis in this study will provide insight into the management of in vitro findings for transporter substrate or inhibitor drugs.