Signal Detection of Adverse Events Associated with Four Dihydropyridine Calcium Channel Blockers Based on the FAERS...

Objectives: As widely used first-line antihypertensive drugs, dihydropyridine calcium channel blockers (DHP-CCBs) have relatively few studies comparing their adverse reactions based on real-world data. This study aims to identify and compare the potential adverse drug reaction (ADR) signals of four DHP-CCBs (amlodipine, felodipine, nicardipine, and nifedipine) through the US Food and Drug Administration Adverse Event Reporting System (FAERS), providing a reference for further drug safety assessment and clinical medication risk awareness. Methods: Adverse event reports from medical professionals (Q3 2014-Q4 2024) were analyzed using signal detection methods, including reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC), and the Medicines and Healthcare Products Regulatory Agency (MHRA) methods. Risk signals for the four DHP-CCBs were compared with both the full database and the DHP-CCBs background. For high-risk signals in amlodipine, multivariate logistic regression was used for validation. The analysis reveals distinct ADR profiles for the four DHP-CCBs. Results: Amlodipine is strongly linked to suicide-related risks, confirmed by logistic regression. Nicardipine and nifedipine show significant risks for pregnancy-related events, such as premature delivery and exposure during pregnancy. Nicardipine is also associated with hyponatremia, hyperkalemia, and lactic acidosis. These adverse events are not yet included in the FDA labeling for any of the DHP-CCBs. Although palpitations and angioedema are listed for felodipine, their signal strength is much higher compared to the other DHP-CCBs. Conclusions: The ADR risk profiles of the four DHP-CCBs differ significantly. This study identified several high-risk adverse events not included in current labels. Clinical use should consider each drug's risk profile and patient-specific factors, with particular attention to serious risk signals. For pregnant and postpartum women, the benefits and risks of using nicardipine and nifedipine should be carefully evaluated.