Signal Detection of Adverse Drug Reactions of Cephalosporins Using Data from a National Pharmacovigilance Database.

Jung-Yoon Choi,Myeong-Gyu Kim,Sandy-Jeong Rhie,Jae-Hee Choi

doi:10.3390/ph14050425

Abstract

This case-non-case study aims to detect signals not currently listed on cephalosporin drug labels. From 2009 to 2018, adverse event (AE) reports concerning antibacterial drugs (anatomical therapeutic chemical (ATC) code J01) in the Korea Adverse Events Reporting System (KAERS) database were examined. For signal detection, three indices of disproportionality, proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC), were calculated. The list of signals was compared with ADRs on the drug labels from the United States, United Kingdom, Japan, and South Korea. A total of 163,800 cephalosporin–AE combinations and 72,265 all other J01–AE combinations were analyzed. This study detected 472 signals and 114 new signals that are not included on the drug labels. Cefatrizine–corneal edema (PRR, 440.64; ROR, 481.67; IC, 3.84) and cefatrizine–corneal ulceration (PRR, 346.22; ROR, 399.70; IC, 4.40) had the highest PRR, ROR, and IC among all signals. Additionally, six serious AEs that were not listed on drug labels such as cefaclor-induced stupor (ten cases) and cefaclor-induced respiratory depression (four cases) were found. Detecting signals using a national pharmacovigilance database is useful for identifying unknown ADRs. This study identified signals of cephalosporins that warrant further investigation.

Highlights

Published: 2 May 2021Cephalosporins are one of the most commonly used antibiotics in clinical practice [1].Cephalosporins are generally considered safe; but allergic reactions, renal dysfunction, hepatic dysfunction, and seizures have occurred as cephalosporin-class adverse reactions and are listed on the drug labels
Serious adverse event (AE) of cephalosporins accounted for 6.76%, most of which caused hospitalization or prolonged hospitalization (48.71%)
We focused on serious adverse events that were clinically meaningful

Summary

Introduction

Cephalosporins are generally considered safe; but allergic reactions, renal dysfunction, hepatic dysfunction, and seizures have occurred as cephalosporin-class adverse reactions and are listed on the drug labels. These adverse drug reactions (ADRs) are responsible for morbidity and mortality and represent a significant burden to both the affected patient and to the health care system [2,3]. Short testing periods and small numbers of subjects in clinical trials hinder identification of all ADRs before marketing [4]. For this reason, investigation of post-marketing adverse events (AEs) is necessary to ensure the safety of the drug.

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