Recommendations for the selection of nucleoside analogues as antihuman
herpesvirus drugs: A real-world analysis of reported cases from the FDA
adverse event reporting system
Caixia Gao1,#, Xiaomei Dong1,#,
Jun Zhang1,3, Lejiao Mao1, Changxin
Guo2, Xia Qin4*#,Zhen
Zou1,3*#
1Molecular Biology Laboratory of Respiratory Disease,
Institute of Life Sciences, Chongqing Medical University, Chongqing
400016, P.R. China.
2Department of Health Laboratory Technology, School of
Public Health, Chongqing Medical University, Chongqing 400016, People’s
Republic of China.
3Research Center for Environment and Human Health,
School of Public Health, Chongqing Medical University, Chongqing 400016,
People’s Republic of China.
4Department of Pharmacy, The First Affiliated Hospital
of Chongqing Medical University, Chongqing 400016, People’s Republic of
China.
# contributed equally
* Correspondence:
Zhen Zou, PD.
zouzhen@cqmu.edu.cn
Xia Qin, MD.
qinxia@cqmu.edu.cn
Keywords: Nucleoside analogues 1,
FAERS2, Human herpesvirus 3, Adverse
drug reactions 4, Signal detection 5.
Abstract
Objective: Based on the discovery and summary of adverse drug
reactions (ADRs) of nucleotide analogues against herpes virus drugs,
this study aims to analyze the situations of ADRs in the real world, put
forward reasonable drug use recommendations, refine the rules of use,
and formulate necessary alternative strategies to provide protection
against herpes virus infection, and provide guidance and reference for
the rational and individualized use of clinical drugs.
Methods: All ADRs data of the drugs from the first quarter of
2004 to the fourth quarter of 2022 were obtained from the FDA Adverse
Event Reporting System (FAERS) database. Duplicate reports, reports with
uncertain information, and other reports containing abnormal information
were excluded from the obtained data, and the data with more than 3
reports were selected. Apply the Reporting odds ratio (ROR),
Proportional reporting ratio (PRR), and Bayesian confidence progressive
neural network method (BCPNN) in the disproportionality analysis for
data mining .
Results: All data from the first quarter of 2004 to the fourth
quarter of 2022 were screened from the FAERS database, and a total of
8420, 11625, 3115, and 344 ADEs related reports were obtained for
Acyclovir (ACV), Valaciclovir (VACV), Ganciclovir (GCV) and Famciclovir
(FCV), respectively. For ADEs with high frequency SOC level, we found
that several important signals, including ADEs of ACV, GCV and VACV,
simultaneously involved the following SOC systems: kidney and urinary
system diseases, nervous system disease, skin and subcutaneous tissue
diseases and mental diseases; ADEs of ACV, VACV and FCV are involved in
nervous system disease; The only drugs that affect injuries, poisoning,
surgical complications, infections and invasions, and disorders of the
blood and lymphatic systems are GCV; FAV is involved in the SOC system
of heart diseases; The SOC system involved in gastrointestinal diseases
is VACV. For ADEs with strongly correlated SOC levels, only ACV is
involved in benign, malignant, and unknown tumors (including cysts and
polyps); GCV is involved in metabolic and nutritional disorders,
gastrointestinal dysfunction, and pregnancy, postpartum, and perinatal
conditions; FAV is involved in skin and subcutaneous tissue diseases,
heart diseases; and VACV is involved in mental diseases. All detected
safety signals are confirmed using disproportionate signal reporting
methods.
Conclusion: The safety reports of the nucleoside analogues
”Lovir” family of drugs are variable. Analysis of the FAERS database
suggests that in addition to paying attention to efficacy, drug
administration should be individualized according to the specific
condition and potential risk of disease.