Database Commons

a catalog of worldwide biological databases

One challenge in the development of novel drugs is their interaction with potential off-targets, which can cause unintended side-effects, that can lead to the subsequent withdrawal of approved drugs. At the same time, these off-targets may also present a chance for the repositioning of withdrawn drugs for new indications, which are potentially rare or more severe than the original indication and where certain adverse reactions may be avoidable or tolerable. To enable further insights into this topic, we updated our database Withdrawn by adding pharmacovigilance data from the FDA Adverse Event Reporting System (FAERS), as well as mechanism of action and human disease pathway prediction features for drugs that are or were temporarily withdrawn or discontinued in at least one country. As withdrawal data are still spread over dozens of national websites, we are continuously updating our lists of discontinued or withdrawn drugs and related (off-)targets. Furthermore, new systematic entry points for browsing the data, such as an ATC tree, were added, increasing the accessibility of the database in a user-friendly way. Withdrawn 2.0 is publicly available without the need for registration or login at https://bioinformatics.charite.de/withdrawn_3/index.php.

Post-marketing drug withdrawals can be associated with various events, ranging from safety issues such as reported deaths or severe side-effects, to a multitude of non-safety problems including lack of efficacy, manufacturing, regulatory or business issues. During the last century, the majority of drugs voluntarily withdrawn from the market or prohibited by regulatory agencies was reported to be related to adverse drug reactions. Understanding the underlying mechanisms of toxicity is of utmost importance for current and future drug discovery. Here, we present WITHDRAWN, a resource for withdrawn and discontinued drugs publicly accessible at http://cheminfo.charite.de/withdrawn. Today, the database comprises 578 withdrawn or discontinued drugs, their structures, important physico-chemical properties, protein targets and relevant signaling pathways. A special focus of the database lies on the drugs withdrawn due to adverse reactions and toxic effects. For approximately one half of the drugs in the database, safety issues were identified as the main reason for withdrawal. Withdrawal reasons were extracted from the literature and manually classified into toxicity types representing adverse effects on different organs. A special feature of the database is the presence of multiple search options which will allow systematic analyses of withdrawn drugs and their mechanisms of toxicity. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.