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Pharmacovigilance assessment of drug-induced aplastic anemia: analysis of the FDA adverse event reporting system.

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Titel: Pharmacovigilance assessment of drug-induced aplastic anemia: analysis of the FDA adverse event reporting system.
Autoren: Zhang F; Department of Hematology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, China., Wang P; Department of Neurology and Geriatric Rehabilitation, Liaoning Provincial First Veterans' and Preferential Treatment Hospital, Shenyang, China., Liu X; Department of Hematology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, China., Chen Y; Department of Cardiothoracic Surgery, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, China., Yang J; Continuing Education College, Liaoning University of Traditional Chinese Medicine, Shenyang, China. lnzyyj1129@163.com.
Quelle: International journal of clinical pharmacy [Int J Clin Pharm] 2025 Dec; Vol. 47 (6), pp. 1967-1978. Date of Electronic Publication: 2025 Sep 29.
Publikationsart: Journal Article
Sprache: English
Info zur Zeitschrift: Publisher: Springer Country of Publication: Netherlands NLM ID: 101554912 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2210-7711 (Electronic) NLM ISO Abbreviation: Int J Clin Pharm Subsets: MEDLINE
Imprint Name(s): Original Publication: Dordrecht : Springer
MeSH-Schlagworte: Pharmacovigilance* , Anemia, Aplastic*/chemically induced , Anemia, Aplastic*/epidemiology , Anemia, Aplastic*/diagnosis , Adverse Drug Reaction Reporting Systems*/statistics & numerical data , United States Food and Drug Administration* , Drug-Related Side Effects and Adverse Reactions*/epidemiology , Drug-Related Side Effects and Adverse Reactions*/diagnosis, Humans ; Male ; Female ; United States/epidemiology ; Retrospective Studies ; Middle Aged ; Adult ; Aged ; Young Adult ; Adolescent ; Child ; Risk Factors ; Child, Preschool
Abstract: Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: This study utilized publicly available de-identified data from FAERS. Since no patient-identifiable information was accessed, institutional ethics approval was not required.
Introduction: Aplastic anemia is a rare but life-threatening disorder often triggered by drug exposure. Given its low incidence, identifying drug-associated risks requires large-scale real-world data. The FDA Adverse Event Reporting System (FAERS) is a valuable pharmacovigilance resource for detecting rare and serious drug reactions.
Aim: This study aimed to evaluate the association between a broad range of medications and the risk of drug-induced aplastic anemia using FAERS data obtained through disproportionality analysis, regression modeling, time-to-onset analysis, and predictive modeling.
Method: A retrospective pharmacovigilance study was conducted using FAERS reports from January 1, 2004, to December 31, 2024. Aplastic anemia cases were identified using five Preferred Terms from the Medical Dictionary for Regulatory Activities. Signal detection was performed using ROR, PRR, BCPNN, and MGPS. Logistic regression analyses with weighted LASSO variable selection identified the independent risk factors. A predictive model was developed and validated using receiver operating characteristic (ROC) curve analysis. Time-to-onset (TTO) and pharmacological classification were also conducted.
Results: A total of 4493 drug-related aplastic anemia cases were identified. Disproportionality analysis revealed 593 significant drugs, of which 16 met stringent inclusion criteria for multivariate analysis. Temozolomide was most frequent (n = 148), followed by methotrexate (n = 126), busulfan (n = 100), and linezolid (n = 90). Other common drugs included ribavirin, nivolumab, pembrolizumab, fludarabine, carboplatin, etoposide, and cyclophosphamide. Male sex was a significant risk factor (OR = 1.63), while older age (> 42 years) and higher weight (> 60 kg) were protective. The predictive model showed good discrimination (AUC = 0.777). Median TTO was 299 days, with most cases occurring within six months. The 16 implicated drugs fell into categories including antineoplastics, antibacterials, antivirals, antiepileptics, and antigout agents.
Conclusion: This study identified key drugs and patient factors associated with aplastic anemia, providing a data-driven framework for pharmacovigilance. These findings support early detection and informed clinical and regulatory decision making, but prospective studies are required to confirm causality and refine individualized risk predictions.
(© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
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Contributed Indexing: Keywords: Adverse drug reaction reporting systems; Aplastic anemia; Drug-related side effects and adverse reactions; Logistic models; Pharmacovigilance; Risk factors; Time-to-onset
Entry Date(s): Date Created: 20250929 Date Completed: 20251119 Latest Revision: 20251119
Update Code: 20251119
DOI: 10.1007/s11096-025-02010-1
PMID: 41021109
Datenbank: MEDLINE
Beschreibung
Abstract:Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: This study utilized publicly available de-identified data from FAERS. Since no patient-identifiable information was accessed, institutional ethics approval was not required.<br />Introduction: Aplastic anemia is a rare but life-threatening disorder often triggered by drug exposure. Given its low incidence, identifying drug-associated risks requires large-scale real-world data. The FDA Adverse Event Reporting System (FAERS) is a valuable pharmacovigilance resource for detecting rare and serious drug reactions.<br />Aim: This study aimed to evaluate the association between a broad range of medications and the risk of drug-induced aplastic anemia using FAERS data obtained through disproportionality analysis, regression modeling, time-to-onset analysis, and predictive modeling.<br />Method: A retrospective pharmacovigilance study was conducted using FAERS reports from January 1, 2004, to December 31, 2024. Aplastic anemia cases were identified using five Preferred Terms from the Medical Dictionary for Regulatory Activities. Signal detection was performed using ROR, PRR, BCPNN, and MGPS. Logistic regression analyses with weighted LASSO variable selection identified the independent risk factors. A predictive model was developed and validated using receiver operating characteristic (ROC) curve analysis. Time-to-onset (TTO) and pharmacological classification were also conducted.<br />Results: A total of 4493 drug-related aplastic anemia cases were identified. Disproportionality analysis revealed 593 significant drugs, of which 16 met stringent inclusion criteria for multivariate analysis. Temozolomide was most frequent (n = 148), followed by methotrexate (n = 126), busulfan (n = 100), and linezolid (n = 90). Other common drugs included ribavirin, nivolumab, pembrolizumab, fludarabine, carboplatin, etoposide, and cyclophosphamide. Male sex was a significant risk factor (OR = 1.63), while older age (&gt; 42 years) and higher weight (&gt; 60 kg) were protective. The predictive model showed good discrimination (AUC = 0.777). Median TTO was 299 days, with most cases occurring within six months. The 16 implicated drugs fell into categories including antineoplastics, antibacterials, antivirals, antiepileptics, and antigout agents.<br />Conclusion: This study identified key drugs and patient factors associated with aplastic anemia, providing a data-driven framework for pharmacovigilance. These findings support early detection and informed clinical and regulatory decision making, but prospective studies are required to confirm causality and refine individualized risk predictions.<br /> (© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
ISSN:2210-7711
DOI:10.1007/s11096-025-02010-1