Candesartan-Associated Interstitial Lung Disease: A Pharmacovigilance Signal Detection Study Using US FDA Adverse Event Reporting System Data
1
Pharmacy Practice, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, Bangalore, Karnataka, India
Popul. Med. 2026;8(Supplement Supplement 1):
ABSTRACT
BACKGROUND:
Candesartan, an angiotensin receptor blocker, is widely prescribed for hypertension management globally. Signal detection through disproportionality analysis provides a systematic, evidence-based approach to identifying previously unreported or underrecognized drug-adverse event associations in large-scale pharmacovigilance databases.
METHODS:
Adverse event data for Candesartan were extracted from the US FDA Adverse Event Reporting System (FAERS) database (1998–2026) using the OpenVigil data-mining platform. Disproportionality analysis was performed using Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR) algorithms. Positive signals were defined according to the criteria of Evans 2001: PRR≥2, ROR-1.96SE>2, Chi-square>4, with a minimum of 3 adverse event reports. Molecular docking studies were conducted to identify potential protein targets associated with DILD pathogenesis. Key proteins implicated in drug-induced pulmonary fibrosis (TNF, HLA-DRB1, TGFB1) were identified from the STITCH, STRING, and HuGE Navigator databases. Binding affinity calculations were performed using BIOVIA Discovery Studio, PyRx, PyMOL, and Swiss PDB Viewer.
RESULTS:
Among 32493748 total adverse events in the FAERS database, 9274 were linked to Candesartan since FDA approval in 1998. 43 cases of interstitial lung disease were identified through OpenVigil analysis. Disproportionality analysis confirmed a positive signal with PRR of 4.674 (3.47 ;6.295), ROR of 4.708 (3.486; 6.358), and Chi-squared with Yates' correction of 120.57, exceeding all predefined positive signal thresholds. Molecular docking analysis revealed three proteins with strong binding affinities: TNF (−9.8 kcal/mol), HLA-DRB1 (−7.2 kcal/mol), and TGFB1 (−6.2 kcal/mol). These findings suggest potential immunological mechanisms, involving T-cell-mediated hypersensitivity and pro-fibrotic pathway activation.
CONCLUSIONS:
Disproportionality analysis confirmed a significant pharmacovigilance signal for Candesartan-associated interstitial lung disease. Molecular docking data provide mechanistic insights into potential immunologically mediated pathways linking angiotensin receptor blockade to pulmonary fibrosis. Further prospective pharmacoepidemiologic and pharmacogenetic studies are warranted to establish causality and elucidate genetic predisposition mechanisms in at-risk populations. This pilot study serves as a reference for the researchers.
Candesartan, an angiotensin receptor blocker, is widely prescribed for hypertension management globally. Signal detection through disproportionality analysis provides a systematic, evidence-based approach to identifying previously unreported or underrecognized drug-adverse event associations in large-scale pharmacovigilance databases.
METHODS:
Adverse event data for Candesartan were extracted from the US FDA Adverse Event Reporting System (FAERS) database (1998–2026) using the OpenVigil data-mining platform. Disproportionality analysis was performed using Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR) algorithms. Positive signals were defined according to the criteria of Evans 2001: PRR≥2, ROR-1.96SE>2, Chi-square>4, with a minimum of 3 adverse event reports. Molecular docking studies were conducted to identify potential protein targets associated with DILD pathogenesis. Key proteins implicated in drug-induced pulmonary fibrosis (TNF, HLA-DRB1, TGFB1) were identified from the STITCH, STRING, and HuGE Navigator databases. Binding affinity calculations were performed using BIOVIA Discovery Studio, PyRx, PyMOL, and Swiss PDB Viewer.
RESULTS:
Among 32493748 total adverse events in the FAERS database, 9274 were linked to Candesartan since FDA approval in 1998. 43 cases of interstitial lung disease were identified through OpenVigil analysis. Disproportionality analysis confirmed a positive signal with PRR of 4.674 (3.47 ;6.295), ROR of 4.708 (3.486; 6.358), and Chi-squared with Yates' correction of 120.57, exceeding all predefined positive signal thresholds. Molecular docking analysis revealed three proteins with strong binding affinities: TNF (−9.8 kcal/mol), HLA-DRB1 (−7.2 kcal/mol), and TGFB1 (−6.2 kcal/mol). These findings suggest potential immunological mechanisms, involving T-cell-mediated hypersensitivity and pro-fibrotic pathway activation.
CONCLUSIONS:
Disproportionality analysis confirmed a significant pharmacovigilance signal for Candesartan-associated interstitial lung disease. Molecular docking data provide mechanistic insights into potential immunologically mediated pathways linking angiotensin receptor blockade to pulmonary fibrosis. Further prospective pharmacoepidemiologic and pharmacogenetic studies are warranted to establish causality and elucidate genetic predisposition mechanisms in at-risk populations. This pilot study serves as a reference for the researchers.
| eISSN: | 2654-1459 |
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