Relevance of physicochemical properties and functional pharmacology data to predict the clinical safety profile of direct oral anticoagulants

In this study we have investigated the relevance of molecular structure and on/off ‐target pharmacology as a predictor of adverse drug reactions (ADRs) for the DOAC drug class. Use of the Reaxys MedChem module allowed for data mining of all possible reported off‐target effects of the DOAC class members. For the first time, the MHRA Yellow card database in combination with pres cribing rates in the United Kingdom (data for n = 30 566 936 DOACRx (up to 2017) and ADR data n  = 22 275 (up to 2018)) were used for our data comparison of DOACs. From the underlying reported data, we were able to rank the DOACs in terms of the likely adverse events we would expect to observe. We identified potential risks of ADRs based on the DOACs pharmacology including the expected GI h emorrhage, but also the unexpected risk of stroke, pulmonary embolism and kidney injury. Statistically significant (P <  .001) differences were found between all DOACs and their total number of ADRs. Although the risks are small, strong statistical correlation between observed pharmacology and national ADR data is observed in three out of the five areas of concern.
Source: Pharmacology Research and Perspectives - Category: Drugs & Pharmacology Authors: Tags: ORIGINAL ARTICLE Source Type: research