Severe cutaneous adverse reactions to drugs: A real-world pharmacovigilance study using the FDA Adverse Event Reporting System database

Abstract

Background: Sound drug safety information is important to optimize patient management, but the widely recognized comprehensive landscape of culprit-drugs that cause severe cutaneous adverse reactions (SCARs) is currently lacking.Objective: The main aim of the study is to provide a comprehensive landscape of culprit-drugs for SCARs to guide clinical practice.Methods: We analyzed reports associated with SCARs in the FDA Adverse Event Reporting System database between 1 January 2004 and 31 December 2021 and compiled a list of drugs with potentially serious skin toxicity. According to this list, we summarized the reporting proportions of different drugs and drug classes and conducted disproportionality analysis for all the drugs. In addition, the risk characteristic of SCARs due to different drugs and drug classes was summarized by the positive–negative distribution based on the results of the disproportionality analysis.Results: A total of 77,789 reports in the FDA Adverse Event Reporting System database were considered SCAR-related, of which lamotrigine (6.2%) was the most reported single drug followed by acetaminophen (5.8%) and allopurinol (5.8%) and antibacterials (20.6%) was the most reported drug class followed by antiepileptics (16.7%) and antineoplastics (11.3%). A total of 1,219 drugs were reported as culprit-drugs causing SCARs in those reports, and the largest number of drugs belonged to antineoplastics. In disproportionality analysis, 776 drugs showed at least one positive pharmacovigilance signal. Drugs with the most positive signals were lamotrigine, acetaminophen, furosemide, and sulfamethoxazole/trimethoprim.Conclusion: Our study provided a real-world overview of SCARs to drugs, and the investigation of SCAR positive–negative distribution across different drugs revealed its risk characteristics, which may help optimize patient management.

Contrastive analysis on the safety of brand and generic nebivolol: a real-world pharmacovigilance study based on the FDA adverse event reporting system

“…A positive ADR signal is defined as the number of AE reports greater than or equal to 3 (a ≥3 in Table 1 ) and the lower-bound 95% CI of ROR value greater than 1, while a negative signal is defined as the number of AE reports or the lower-bound 95% CI of ROR value cannot reach above criterion ( Li et al, 2023 ). Besides, referring to previous literature ( Rahman et al, 2017a ), the Breslow-Day test was used to test the heterogeneity of ROR between GN and BN, and significantly statistical difference was existed when p < 0.01.…”

“…The pharmacovigilance databases are widely used to conduct post-marketing surveillance of drugs in the real world and to provide the public with information on possible adverse drug events (AEs). In this regard, the FDA Adverse Event Reporting System (FAERS) database, a database with a large population, comprehensive geographic coverage, and publicly available accessibility, has become one of the essential data sources that is commonly used for research in the field of pharmacovigilance ( Li et al, 2023 ). Meanwhile, previous literature has also confirmed the feasibility of using FAERS to explore safety differences between generic drugs and brands ( Rahman et al, 2017b ; Cheng et al, 2018 ).…”

Drug-induced QT prolongation and torsade de pointes: a real-world pharmacovigilance study using the FDA Adverse Event Reporting System database

“…Referring to the number of cases and the value of the lower limit of 95% CI, the ADR signal detection results can be further classified into negative and positive signals. A signal is considered positive when there are at least three cases (a ≥3 in Table 2) and the lower limit of 95% CI > 1, while a signal is considered negative when the number of cases or the lower limit of 95% CI cannot meet the aforementioned criteria (Li et al, 2023a).…”

“…Pharmacovigilance is the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other possible drug-related problems, and currently, using real-world data in pharmacovigilance databases to explore and summarize drug risk characteristics has become an important measure to evaluate drug safety (Beninger, 2018;Lucas et al, 2022). To some extent, it can break the inherent limitations of size, duration, and population selection in preclinical research and provide a real-time overview of main toxicities in a cost-effective manner, thereby providing information for clinical practice (Li et al, 2023a). In this respect, the FDA Adverse Event Reporting System (FAERS) database, a freely accessible pharmacovigilance database with massive real-world data and wide geographic coverage, provides an unprecedented opportunity to comprehensively investigate and summarize the risk of QT prolongation and TdP triggered by drugs.…”

Drug‐Induced Acute Pancreatitis: A Real‐World Pharmacovigilance Study Using the FDA Adverse Event Reporting System Database

“…To a certain extent, the more positive ADR signals a drug has, the more attention should be paid to the AP risk of the drug. 33,50 On the other hand, we integrated the positive-negative distribution characteristics of ADR signals at…”