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 Gao^1,#, Xiaomei Dong^1,#, Jun Zhang^1,3, Lejiao Mao¹, Changxin Guo², Xia Qin^4*#，Zhen Zou^1,3*#

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.