An Audit of Black Box Warnings (BBWs) in the United States Food and Drug Administration (US-FDA) Database - A Five-Year Analysis

Background: The Black-Box Warning (BBW) is the most serious warning that US-FDA can ask for on a drug’s labelling. BBWs represent key safety concerns uncovered either during dossier review or post-approval. We have conducted the present study with the primary objective of assessing BBWs issued by the US-FDA. Methods: BBWs were identified on US-FDA’s website from 1st January 2015 to 31st December, 2019. Prescribing information was used to identify and characterize BBWs into new and minor/major updates on a previous BBW. The therapeutic class of the drug, nature [Biological/New Molecular entity (NME)], formulation type, expected duration of use, along with the year of first approval of the molecule with BBWs were evaluated. Results: A total of n = 167 BBWs were issued by the FDA of which 53 (31.7%) had major updates, 57(34.1%) had minor updates and 57(34.1%) were new BBWs. A total of 137(82%) of BBWs were with NME’s whereas 30(18%) were with biologics. Drugs for neurology 40(25.5%)had the highest number of BBWs, followed by oncology 38(24.2%). Among the type of BBWs, cardiovascular risk 31 (15%) were the highest. Conclusion: Practicing physicians need to understand that benefit-risk of a drug is dynamic and keep abreast of new data related to it.