Drug safety information: Boxed warnings and Withdrawn drugs

Updated drug safety information is available (as of ChEMBL 28) for drugs with boxed warnings and for withdrawn drugs.

Boxed warnings (also know as black box warnings) are provided on medicinal product labels for FDA approved drugs if the medicinal product can cause severe or life-threatening side effects. They are free text descriptions, enclosed within a black box, hence the name! For example, Oxaprozin is used to treat osteoarthritis but carries a boxed warning.

Our recent work has classified the type of adverse effect described in boxed warnings on a per drug basis. For medicinal products that contain one active pharmaceutical ingredient, a boxed warning can be directly linked to a drug. Therefore, toxicity class(es) have been assigned to approved drugs with boxed warning information described on medicinal product labels (e.g. Cardiotoxicity, Hepatotoxicity etc). Clickable links to examples of medicinal product labels with boxed warning text descriptions have been retained to allow database users to drill down through the information “audit trail” to examine the source information. Further details are available from Hunter et al., 2021.

As part of this effort, source references for previously curated withdrawn drugs have also been publicly exposed, ie drugs that have been approved but subsequently withdrawn from one or more markets of the world for safety reasons. See our blog on Withdrawn Drugs.

All safety information can be accessed in the ChEMBL web interface via the Drugs view (which is grouped by parent compound) or via the Compound view (for either view, filter on the left hand side by 'withdrawn flag' or 'black box warning'). For an individual drug, detailed drug warning information and source references are available on the Compound Report Card, e.g. Tolcapone, CHEMBL1324, is approved to treat Parkinson's Disease but carries a warning of Hepatotoxicity:

Programatic access is also available via our new Drug_Warning API endpoint, e.g. a search for hepatotoxic drugs (either withdrawn or those with a boxed warning) could apply this syntax:

https://www.ebi.ac.uk/chembl/api/data/drug_warning.json?warning_class=Hepatotoxicity

The drug safety information allows drugs that cause similarly reported toxicities to be easily grouped, analyzed, and visualized. The ChEMBL resource contains a wide range of bioactivity data types, from early “Discovery” stage preclinical data for individual compounds through to postclinical data on marketed drugs; the inclusion of the drug safety information within this framework can support a wide range of safety-related drug discovery questions. The drug safety information will be updated in future database releases.

This work has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 116030. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.

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