Adverse Reaction Signals Research Articles

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

Introduction: Drug-induced QT prolongation and (or) Torsade de Pointes (TdP) is a well-known serious adverse reaction (ADR) for some drugs, but the widely recognized comprehensive landscape of culprit-drug of QT prolongation and TdP is currently lacking. Aim: To identify the top drugs reported in association with QT prolongation and TdP and provide information for clinical practice. Method: We reviewed the reports related to QT prolongation and TdP in the FDA Adverse Event Reporting System (FAERS) database from January 1, 2004 to December 31, 2022, and summarized a potential causative drug list accordingly. Based on this drug list, the most frequently reported causative drugs and drug classes of QT prolongation and TdP were counted, and the disproportionality analysis for all the drugs was conducted to in detect ADR signal. Furthermore, according to the positive-negative distribution of ADR signal, we integrated the risk characteristic of QT prolongation and TdP in different drugs and drug class. Results: A total of 42,713 reports in FAERS database were considered to be associated with QT prolongation and TdP from 2004 to 2022, in which 1,088 drugs were reported as potential culprit-drugs, and the largest number of drugs belonged to antineoplastics. On the whole, furosemide was the most frequently reported drugs followed by acetylsalicylic acid, quetiapine, citalopram, metoprolol. In terms of drug classes, psycholeptics was the most frequently reported drug classes followed by psychoanaleptics, analgesics, beta blocking agents, drugs for acid related disorders. In disproportionality analysis, 612 drugs showed at least one positive ADR signals, while citalopram, ondansetron, escitalopram, loperamide, and promethazine were the drug with the maximum number of positive ADR signals. However, the positive-negative distribution of ADR signals between different drug classes showed great differences, representing the overall risk difference of different drug classes. Conclusion: Our study provided a real-world overview of QT prolongation and TdP to drugs, and the presentation of the potential culprit-drug list, the proportion of reports, the detection results of ADR signals, and the distribution characteristics of ADR signals may help understand the safety profile of drugs and optimize clinical practice.

Real-World Data in Pharmacovigilance Database Provides a New Perspective for Understanding the Risk of Clostridium difficile Infection Associated with Antibacterial Drug Exposure.

Antibacterial drug exposure (ADE) is a well-known potential risk factor for Clostridium difficile infection (CDI), but it remains controversial which certain antibacterial drugs are associated with the highest risk of CDI occurrence. To summarize CDI risk associated with ADE, we reviewed the CDI reports related to ADE in the FDA Adverse Event Reporting System database and conducted disproportionality analysis to detect adverse reaction (ADR) signals of CDI for antibacterial drugs. A total of 8063 CDI reports associated with ADE were identified, which involved 73 antibacterial drugs. Metronidazole was the drug with the greatest number of reports, followed by vancomycin, ciprofloxacin, clindamycin and amoxicillin. In disproportionality analysis, metronidazole had the highest positive ADR signal strength, followed by vancomycin, cefpodoxime, ertapenem and clindamycin. Among the 73 antibacterial drugs, 58 showed at least one positive ADR signal, and ceftriaxone was the drug with the highest total number of positive signals. Our study provided a real-world overview of CDI risk for AED from a pharmacovigilance perspective and showed risk characteristics for different antibacterial drugs by integrating its positive-negative signal distribution. Meanwhile, our study showed that the CDI risk of metronidazole and vancomycin may be underestimated, and it deserves further attention and investigation.

Adverse reaction signals mining and hemorrhagic signals comparison of ticagrelor and clopidogrel: A pharmacovigilance study based on FAERS.

Background: Ticagrelor and clopidogrel are commonly used antiplatelet agents, and we conducted a pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS) to provide a reference for safe and reasonable clinical use. Methods: Data were collected in FAERS from 2012 Q1 to 2022 Q2 for data cleaning. We used system organ classes (SOCs) and prefer terms (PTs) from the Medical Dictionary of Regulatory Activity (MedDRA version 25.1). Adverse event reports were retrieved at the PT level. Adverse reaction (ADR) signals of ticagrelor and clopidogrel were mined by calculating reporting odds ratios (ROR), proportional reporting ratios (PRR), information component (IC) and empirical Bayesian geometric mean (EBGM). After that, further analysis of the hemorrhagic signals and their clinical information were performed. Results: The number of ADR reports where the primary suspect (PS) drugs were 15,133 for ticagrelor and 23,860 for clopidogrel. Significant ADR signals were identified by the SOC analysis for ticagrelor including cardiac disorders (ROR 4.87, PRR 4.46), respiratory disorders (ROR 2.45, PRR 2.28), and vascular disorders (ROR 2.22, PRR 2.16). Clopidogrel included blood disorders (ROR 2.86, PRR 2.77), vascular disorders (ROR 2.71, PRR 2.61), and cardiac disorders (ROR 2.29, PRR 2.22). At the PT level, the more frequent ADR signals for ticagrelor were dyspnoea, contusion, and haemorrhage, while clopidogrel were gastrointestinal haemorrhage, anaemia, and drug interaction. The hemorrhagic signals of both were mainly focused on the SOC level of gastrointestinal disorders, injury disorders and vascular disorders and nervous system disorders. The death and life-threatening rate of ticagrelor was 7.76 percentage higher than that of clopidogrel. Conclusion: Clinicians need to pay attention to not only common ADRs but also be alert to new ADR signals when choosing to use ticagrelor and clopidogrel. This study provides a reference for the reasonable and safe clinical use of ticagrelor and clopidogrel.

Analysis on 1 500 adverse reactions of Guizhi Fuling Capsules based on spontaneous response system

To understand the characteristics of adverse reactions and find early warning signs after intake of Guizhi Fuling Capsules. The 1 500 adverse reaction(ADR) cases of Guizhi Fuling Capsules obtained by spontaneous reporting system(SRS) from 2008 to 2017 were analyzed by proportional reporting ratios method(PRR), Bayesian confidence propagation neural network method(BCPNN) and propensity score method. The number of ADR reports increased year by year, and reached the peak in the fourth quarter of 2014. A total of 1 500 ADR cases were monitored, including 10 severe ADR cases. There were a total of 934 cases aged between 18-44 years old, accounting for 62.27%. All patients were orally administered. Among them, 1 398 patients received a single dose according to the package insert, and 57.4% had ADR within 24 h. The top five clinical manifestations of ADR were gastric dysfunction, abdominal pain, nausea, vomiting and rash, which mainly damaged the digestive system. The ADR signals were analyzed. PRR suggested that "gastric dysfunction" and "abdominal pain" were the early warning signals of Guizhi Fuling Capsules. BCPNN suggested that "nausea" and "abdominal pain" were the early warning signals of Guizhi Fuling Capsules. After the propensity score weighting method was used to control the confounding factors, the warning signals remained unchanged. The results show that Guizhi Fuling Capsules has fewer adverse reactions and is relatively safe. This study provides a basis for studying ADR of Guizhi Fuling Capsules, and guidance for drug vigilance and risk management of Guizhi Fuling Capsules.