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.