A Longitudinal Analysis of Black Box Warnings: Trends and Implications for Drug Safety

Abstract

A black box warning, signaling potential life-threatening adverse effects of medications or medical devices, is crucial for public and healthcare professional awareness. Comprehending and adhering to these warnings can prevent serious harm. This review aims to elucidate their significance. Data on drugs with black box warnings were collected from the Food and Drug Administration's (FDA's) official website using the search term 'Boxed warnings' from January 1, 2015, to January 31, 2024. A Microsoft Excel spreadsheet (Microsoft Corporation, Redmond, WA, USA) containing black box warnings for this period was downloaded from the FDA's website. Additional parameters, such as drug class and whether the warnings were new or existing, were added to the downloaded spreadsheet. The collected data were organized by year, categorizing new and existing warnings, along with details on the evidence source, system-wise classification, and black box warnings for commonly used drugs, including their clinical significance. Results show that in the past decade, 40% of black box warnings were issued in 2023, followed by 12% in 2022. Most warnings (67%) comprised existing ones with minor revisions while 29% were new. Nine existing warnings were removed during the period. Post-marketing studies predominantly provided evidence for these warnings. Neuropsychiatric concerns like addiction potential (31%), suicidal tendency (7%), and hypersensitivity reactions (12%) were the frequently encountered black box warnings. Black box warnings play a crucial role in highlighting the serious adverse effects of medications. Neuropsychiatric warnings have been frequent over the past decade. Awareness of these warnings is essential to prevent adverse effects and enhance patient care, especially concerning drugs like guaifenesin/hydrocodone bitartrate, zolpidem, and montelukast commonly encountered in clinical practice.

Keywords: adverse events (ae); black box warnings; drug label; drugs; post-marketing studies.

Figure 1. Process of black box warning

Source: [1] The figure is not republished work. The content is extracted from the cited reference and condensed in the form of a figure by the authors.

Figure 2. The data extraction workflow

Image created by the authors

Figure 3. Year-wise distribution of black box warnings

Source: [7] The figure is not republished work. The content is extracted from the cited reference and condensed in the form of a figure by the authors.

Figure 4. Categorization of drugs as per the class

[7] The figure is not republished work. The content is extracted from the cited reference and condensed in the form of a figure by the authors.