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Tuesday, 12 June 2018

Withdrawn Drugs


These is much ongoing work within the drug discovery and toxicology communities to better understand the safety aspects of approved drugs and clinical candidate compounds, and for this reason there is clear interest in why some drugs have been approved but then subsequently withdrawn from the market. This post describes the information for withdrawn drugs that is currently available in ChEMBL. 

Within ChEMBL (release 24) there are 192 drugs that have been annotated as approved but then subsequently withdrawn from the market for one or more reasons.  For each of these drugs, the year of withdrawal, region of withdrawal and reason for withdrawal (‘withdrawn_reason’) have been available since release 22 of ChEMBL (see ftp://ftp.ebi.ac.uk/pub/databases/chembl/ChEMBLdb/releases/chembl_22/archived/chembl_22_release_notes.txt), while the classification of the reason for withdrawal (‘withdrawn_class’)  is a new feature for ChEMBL (release 24).  The withdrawn information is available for relevant drugs on the Compound Report Card of the web interface, or within the molecule_dictionary sql table. 

For example Rosiglitazone, an anti-diabetes medicine, was withdrawn from the EU in 2011 due to the increased risk of ischaemic heart disease (http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2010/09/news_detail_001119.jsp ). Note that Rosiglitazone has been withdrawn from the EU market, but is still available within other regions of the world and hence the Compound Report Card shows that the drug is ‘approved’ (see information within the top of the Compound Report Card - https://www.ebi.ac.uk/chembl/compound/inspect/CHEMBL121), while the detail about the region of withdrawal shows that it has been withdrawn from the EU (further down the Compound Report Card). ‘Cardiotoxicity’ is annotated as the withdrawn_class for Rosiglitazone.



Using the withdrawn classification (‘withdrawn_class’), similar withdrawn drugs can be grouped together. For example, if you are interested in approved drugs that have been withdrawn for ‘hepatoxicity’, ‘cardiotoxicity’, ‘neurotoxicity’ etc then you can now easily group drugs withdrawn for similar reasons. Therefore the pie chart displayed below shows 45 drugs that have been withdrawn for hepatotoxicity reasons. 

Of the annotated classes of withdrawn drugs, 37 drugs have more than one reason for withdrawal from the markets (and therefore are assigned more than one class of withdrawn reason on the pie chart); 9 of the withdrawn drugs have not been assigned a withdrawn_class because they have a non-specific reason (e.g. 'Multi-Organ Toxicities') that cannot be given a withdrawn_class without further investigation of the underlying literature; and 44 of the withdrawn drugs do not currently have a reason described in ChEMBL. 

Further work is planned to annotate additional withdrawn drug information. 


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.