OBJECTIVES: This study aimed to explore the novel signals reported for Candesartan in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from April 1998 to June 2024.

METHODS: The data extracted from FAERS database was analysed to identify an unidentified signal or adverse event for Candesartan. The disproportionality analysis was performed using OpenVigil database for identifying the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR). Positive signals were defined as values of PRR≥1, ROR-1.96SE>1 and chisq > 4. The genes and proteins associated with the signal were found out from various databases such as STITCH, STRING and HuGE Navigator. Later these genes were docked with the drug using BIOVIA Discovery Studio, PyRx, Pymol and Swiss PDB viewer.

RESULTS: In FAERS database, a total of 28655483 events were reported. The USFDA approved Candesartan on 6^th of April 1998. Since then, the drug accounted for 6551 events. The OpenVigil data showed 12 events for Osteoarthritis. The PRR was found to be 1.967 (1.11; 3.46) and ROR was 1.97 (1.11; 3.47), which indicated a positive signal. The rate of occurrence of drug event and drug administered is observed to be 0.27% based on the real- world data. The chi-squared value with Yates' correction was found to be 4.78. The genes involved in osteoarthritis according to the databases are CALM1, IL1 and GDF5 with the highest binding affinity of -8.4, -7.9 and -6.8 respectively.

CONCLUSIONS: The results of our study aligned with the specifications to confirm the novel signal osteoarthritis with candesartan. The CALM1, IL1 and GDF5 genes and proteins showed association between candesartan and osteoarthritis. However, further pharmacoepidemiologic and pharmacogenetic analysis are required to establish the mechanism of the reported Adverse Drug Reaction due to the inherent limitations of the FAERS data.