OBJECTIVES: The authors aimed to explore the novel signals reported for Candesartan in the USFDA Adverse Event Reporting System (FAERS) database.

METHODS: In this study, FAERS data was analysed to identify a novel signal for Candesartan. The data mining algorithms like Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR) values were obtained from OpenVigil database. Positive signals were defined as values of PRR≥2, ROR-1.96SE>2, chisq > 4 with more than 2 adverse events. The genes and proteins associated with Stevens Johnson Syndrome were found out from various databases such as STITCH, STRING and HuGE Navigator. Later these genes were docked with Candesartan using BIOVIA Discovery Studio, PyRx, Pymol and Swiss PDB viewer.

RESULTS: A total of 28655483 adverse events are reported in the database. Of these adverse events, 6551 were linked to candesartan. Candesartan got its FDA approval in 1998. The OpenVigil data showed 19 events of Erectile dysfunction for candesartan. The PRR value was found to be 3.50 (2.23; 5.48), ROR was 3.51 (2.23; 5.51), Chi-Squared with Yates' correction was 31.51 which indicated positive signals. The signal was most prevalent among Europeans with 11 events and had a PRR of 2.525 (1.401; 4.553) and ROR of 2.537 (1.401; 4.593). The genes involved in erectile dysfunction according to the bioinformatics databases are eNOS and ACE with the highest binding affinity of -8.7 and -8.6 respectively.

CONCLUSIONS: The binding affinity and the disproportionality results obtained for data mining algorithms confirms erectile dysfunction as adverse reaction of candesartan. However, further pharmacogenetic and prospective pharmacoepidemiologic analysis with extended follow-up are needed to establish the mechanism and prevalence of the reported Adverse Drug Reaction.