US postmarketed drug removals: Analysis of discontinued and withdrawn drugs

Drugs removed from the US market after approval can be either discontinued by the manufacturer or withdrawn by the US Food and Drug Administration (FDA). However, a systematic overview is currently lacking. This minireview provides a comprehensive analysis of removed drugs, identifies patterns regarding drug classes, indications, adverse effects, and scientific interest, and compares US removals with the European Union and FDA boxed warnings. A total of 166 drugs were removed between 1955 and 2026, including 88 discontinued and 78 withdrawn drugs. Removed drugs represented a wide range of therapeutic fields, with certain drug classes occurring repeatedly, particularly cyclooxygenase inhibitors and fluoroquinolones. Market removals were frequently associated with serious adverse effects such as hepatotoxicity, cardiotoxicity, and hematologic toxicity. The prominent drug classes and adverse effect categories also occurred frequently among drugs carrying boxed warnings. While withdrawn drugs were typically banned by the FDA because of severe safety concerns, discontinued drugs were often removed because of commercial decisions or obsolescence, sometimes in combination with safety considerations. The analysis of publication peaks showed that for most drugs, scientific interest peaked before market removal, while in other cases, publication peaks occurred around or after withdrawal, indicating renewed scientific interest. Drug removals from the US market represent a heterogeneous group of drugs, indications, and underlying causes. While withdrawals and discontinuations differ in their regulatory implications, they share overlapping characteristics and safety considerations. Integration of European Union availability and FDA boxed warning comparisons highlights international differences and patterns requiring precautionary attention, with recurring drug classes and adverse effects. SIGNIFICANCE STATEMENT: This minireview provides a comprehensive overview of US postmarketing drug removals, covering drugs and causes, as well as evaluating and comparing their characteristics. Patterns and characteristics are identified and compared between discontinued and withdrawn drugs. The analysis of publication peaks and the derived patterns allow an evaluation of changes in scientific interest. This analysis provides information on past drug safety decisions and guides future risk-benefit assessments, while identifying prevalent drug classes and adverse effects that require precaution.